Inspiratory muscle training for cystic fibrosis

  • Review
  • Intervention

Authors


Abstract

Background

Cystic fibrosis is the most common life-limiting genetic condition in Caucasians and the life-expectancy of those newly diagnosed is increasing. Inspiratory muscle training may be a way of improving the lung function and quality of life of people with cystic fibrosis. Hence there is a need to establish whether this intervention is beneficial.

Objectives

To determine the effect of inspiratory muscle training on health-related quality of life, pulmonary function and exercise tolerance.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Date of most recent search: 08 July 2013.

Selection criteria

Randomised or quasi-randomised clinical controlled trials comparing different inspiratory muscle training regimens with each other or a control in people with cystic fibrosis.

Data collection and analysis

Three review authors independently applied the inclusion and exclusion criteria to publications and assessed the quality of the included studies.

Main results

Fourteen studies were identified. Of these eight studies with 180 participants met the review inclusion criteria. There was wide variation in the quality of the included studies. Data were not published in sufficient detail or with sufficiently similar outcome measures in these studies to perform meta-analyses.

Authors' conclusions

We have not found any evidence to suggest that this treatment is either beneficial or not. We would advise that practitioners evaluate on a case-by-case basis whether or not to employ this therapy. We recommend that future studies make more use of health-related quality of life and exercise tolerance measures; and that there is an agreement upon a single standard measure of classifying the clinical status of the participants.

Résumé scientifique

Inspiratory muscle training for cystic fibrosis

Contexte

La fibrose kystique est la maladie génétique limitant l'espérance de vie la plus courante chez les personnes de race blanche et l'espérance de vie des personnes dont le diagnostic vient d'être posé augmente. L'entraînement des muscles inspirateurs peut être une manière d'améliorer la fonction pulmonaire et la qualité de vie des personnes atteintes de fibrose kystique. Il est donc nécessaire d'établir si cette intervention est bénéfique.

Objectifs

Déterminer l'effet de l'entraînement des muscles inspirateurs sur la qualité de vie liée à la santé, la fonction pulmonaire et la résistance à l'effort.

Stratégie de recherche documentaire

Nous avons effectué une recherche dans le registre d’essais cliniques du groupe Cochrane sur la fibrose kystique et les troubles génétiques constitué des références identifiées lors de recherches exhaustives dans des bases de données électroniques et de recherches manuelles de revues pertinentes et de résumés d’actes de conférence.

Date de la recherche la plus récente : 8 juillet 2013.

Critères de sélection

Essais cliniques contrôlés randomisés ou quasi-randomisés comparant différents programmes d'entraînement des muscles inspirateurs les uns aux autres ou à un témoin chez les personnes atteintes de fibrose kystique.

Recueil et analyse des données

Trois auteurs de revue ont appliqué les critères d'inclusion et d'exclusion à des publications et évalué la qualité des études incluses de manière indépendante.

Résultats principaux

Quatorze études ont été identifiées. Parmi celles-ci, huit études, impliquant 180 participants, répondaient aux critères d'inclusion de la revue. Il y avait de grandes variations dans la qualité des études incluses. Les données n'ont pas été publiées avec suffisamment de détails ou avec critères de jugement suffisamment semblables entre les différentes études pour pouvoir effectuer une méta-analyse.

Conclusions des auteurs

Nous n'avons trouvé aucune preuve suggérant que ce traitement soit bénéfique ou non. Nous conseillerions aux praticiens d'évaluer au cas par cas s'il convient d'utiliser ou non cette thérapie. Nous recommandons que les études à venir utilisent davantage les mesures de la qualité de vie liée à la santé et de résistance à l'effort, et qu'il y ait un accord sur une mesure standard unique pour classer l'état clinique des participants.

Plain language summary

The training of muscles that cause the chest to expand in order to take air into the lungs for people with cystic fibrosis

Cystic fibrosis is the most common life-limiting genetic condition in Caucasians. The life-expectancy of newly diagnosed patients is increasing. Inspiratory muscle training may improve quality of life, lung function and exercise tolerance in people with cystic fibrosis, so that these are closer to the levels found in people who do not have cystic fibrosis. It may also boost the clearance of mucus. Inspiratory muscle training can be performed without the help of a carer and wherever the individual feels appropriate. We searched for randomised or quasi-randomised controlled clinical trials to determine the effects of inspiratory muscle training in the treatment of people with cystic fibrosis. We included eight studies with 180 participants in the review, but we could not combine results from these studies to answer our questions, because the studies either did not publish enough details or did not use the same standard measurements. Given this, we cannot recommend the use, or not, of this intervention. We do recommend that future studies make more use of health-related quality of life and exercise tolerance measures. We also suggest there should be agreement upon standard measurements used.

Résumé simplifié

Entraînement des muscles provoquant le gonflement de la cage thoracique afin d'amener l'air dans les poumons pour les personnes atteintes de fibrose kystique

La fibrose kystique est la maladie génétique limitant l'espérance de vie la plus courante chez les personnes de race blanche. La durée de vie des patients dont le diagnostic vient d'être posé augmente. L'entraînement des muscles inspirateurs peut améliorer la qualité de vie, la fonction pulmonaire et la résistance à l'effort chez les personnes atteintes de fibrose kystique de sorte qu'elles soient plus proches des niveaux observés chez les personnes qui ne souffrent pas de fibrose kystique. Il pourrait également accélérer le dégagement du mucus. L'entraînement des muscles inspirateurs peut se faire sans l'aide d'un soignant et là où la personne le souhaite. Nous avons recherché des essais cliniques contrôlés randomisés ou quasi-randomisés. Nous voulions déterminer les effets de l'entraînement des muscles inspirateurs dans le traitement des personnes atteintes de fibrose kystique. Nous avons pu inclure huit études, impliquant 180 participants, dans la revue. Nous n'avons pas pu combiner les résultats de ces études pour répondre à nos questions, car les études n'avaient pas publié assez de détails ou n'avaient pas utilisé les mêmes critères d’évaluation . De ce fait, nous ne pouvons pas recommander d'utiliser ou de ne pas utiliser cette intervention. Nous recommandons cependant que les études à venir utilisent davantage les mesures de la qualité de vie liée à la santé et de résistance à l'effort. Nous suggérons également qu'il y ait un accord sur les mesures standard à utiliser.

Notes de traduction

Traduit par: French Cochrane Centre 1st December, 2011
Traduction financée par: Ministère du Travail, de l'Emploi et de la Santé Français

Background

Description of the condition

Cystic fibrosis (CF) is the result of a genetic mutation that directly affects ion transport within cells by altering the function of the cystic fibrosis transmembrane conductance regulator (CFTR). In the case of secretory cells, this results in the production of dehydrated, viscous and ultimately dysfunctional secretions (WHO 2005). Two main sites of secretory cells are the digestive and respiratory systems. Both of these systems have a major influence on health and development. The adverse effect on the respiratory system in people with CF contributes to it being the most common, life-limiting autosomal recessive genetic disorder in Caucasians (Kosorok 1996); and in the UK it currently affects over 7500 people (CF Trust 2005). With advancement in the medical management of the condition, the life-expectancy of babies newly diagnosed is now into their fifties (Dodge 2007). This brings with it a responsibility for all clinicians working with people with CF, and in particular physiotherapists, to consider ways of enhancing quality of life.

Description of the intervention

Inspiratory muscle training (IMT) involves the training of muscles that act to expand the chest in order to take in air into the lungs. The specific loads applied to the inspiratory muscles for the purpose of training are flow, threshold or resistive in nature (see Table 1 for explanations of these terms: threshold load, resistive loading). Training regimens vary in terms of intensity and duration of session or programme or both (McConnell 2002). It is possible to develop a training regimen that combines a method of stressing the inspiratory muscles with a specific training approach, e.g. continuous or interval training (see Table 1). Patients can perform IMT independently and wherever they feel it appropriate. While the initial provider and setting for initiating IMT will usually involve a therapist in a clinical setting, generally the user of IMT will be left to implement their own training, with or without supervision from another person, such as a carer.

Table 1. Explanation of terms
TermExplanation
Continuous trainingTraining at 70% to 80% of maximum effort for 30 to 45 minutes. The percentage of maximal effort or the duration of the training (or both) may be adjusted depending on the goal of the training.
Elastic loadRefers to the load imposed by the stiffness of the lung and chest wall that must be overcome by the inspiratory muscles in order to generate inspiratory flow. Elastic loads are greater when breathing from a higher lung volume as a consequence of the associated decrease in lung and chest wall compliance. Imposing elastic loads has not been used to train the inspiratory muscles most likely due to the need for complicated equipment and poor clinical utility.
Forced expiratory volume at 1 second (FEV1)The volume of air expelled during the 1st second of forced exhalation from total lung capacity.
Forced vital capacity (FVC)The total volume of air expelled during a forced exhalation from total lung capacity.
Inspiratory capacity (IC)The maximum volume of air taken into the lungs during a maximal inhalation from functional residual capacity.
Forced expiratory flow 25-75% (FEF25-75%)The speed of the air leaving the lungs during the middle section of a forced exhalation.
Interval trainingPeriods of intense training interspersed with periods of recuperation; as with continuous training, the level of effort required during the training period may be adjusted to suit the individual and the intended goal. The period of recuperation will be adjusted accordingly.
Maximal inspiratory pressure (PImax)The maximum pressure generated by the inspiratory muscles against an occluded airway.
Resistive loadingRequires person to breathe through a narrow inspiratory pathway or aperture. The load imposed is dependent on inspiratory flow, i.e. when using resistive training devices, participants can reduce the load imposed by manipulating their breathing pattern. Breathing pattern, specifically inspiratory flow, should be controlled when using resistive inspiratory muscle training devices.
Threshold loadingRequires the person to inspire through a device which imposes a threshold load via either a weighted plunger system or a spring-loaded valve. The person needs to generate a critical inspiratory pressure, prior to the threshold valve opening and allowing inspiratory flow. Once the threshold valve is open, pressure and flow are largely independent and therefore the person is unable to reduce the load imposed by the device by manipulations in breathing pattern.
Total lung capacity (TLC)The maximum amount of air the lungs can hold when they are fully inflated.
Voluntary isocapnic (normocapnic) hyperpnoeaRequires the person to maintain a high level of minute ventilation for a specified period. Imposes a high flow, low pressure load on the inspiratory muscles which is analogous to the loads borne by the inspiratory muscles during periods of increased minute ventilation (i.e. during exercise). Requires the use of complex equipment to ensure stable levels of carbon dioxide in the arterial blood (PaCO2), so is rarely used in the clinical setting.

How the intervention might work

A Cochrane Systematic Review has found some limited evidence that general conditioning exercise (physical training) can improve the function of the lungs, the exercise tolerance and health-related quality of life of people who have CF closer to that of healthy people (Bradley 2008). More specifically, IMT may also have these benefits (de Jong 2001). In addition, it has been suggested that IMT may also enhance the clearance of mucus, which is fundamental to management of the condition (Chatham 2004).

Why it is important to do this review

Prior to previous versions of this review (Houston 2008; Houston 2009), there was no systematic review of the currently available evidence from randomised controlled trials (RCTs) or quasi-randomised controlled trials as to whether IMT is beneficial, nor on the optimal IMT programme (i.e. the nature of the training load and specifics of the training protocol), for people with CF. This review has now been updated.

Objectives

  1. To determine the effects of IMT in the management of people with CF. Specifically, we plan to examine the effects of IMT in people with CF on:

    1. health-related quality of life;

    2. pulmonary function;

    3. exercise tolerance;

  2. To report any adverse effects reported in the included trials.

  3. To compare the effects of IMT performed using resistive devices, threshold-loading devices and isocapnic hyperpnoea (seeTable 1) on the above outcomes and adherence.

Methods

Criteria for considering studies for this review

Types of studies

Randomised or quasi-randomised clinical controlled trials.

Types of participants

People with CF, of any age, diagnosed by clinical criteria, sweat test or genotyping or both.

Types of interventions

Inspiratory muscle training (as achieved by voluntary isocapnic hyperpnoea, resistive loading or threshold loading: see Table 1) compared with each other or with no or sham IMT (device or procedure that appears to be IMT but does not have its training properties).

Types of outcome measures

Primary outcomes
  1. Health-related quality of life

  2. Pulmonary function tests (performed at rest):

    1. forced expiratory volume at one second (FEV1)

    2. forced vital capacity (FVC)

  3. Exercise tolerance:

    1. field-based tests

    2. laboratory-based tests

Secondary outcomes
  1. Pulmonary function tests (performed at rest):

    1. maximal inspiratory pressure (PImax)

    2. inspiratory capacity (IC)

  2. Respiratory muscle function (strength and endurance)

  3. Frequency and duration of respiratory infections, hospitalisations

  4. Adherence to the IMT regimen

  5. Death or survival

  6. Adverse effects (pneumothorax, musculoskeletal pains or injuries, others)

  7. Costs

Search methods for identification of studies

Electronic searches

We identified relevant studies from the Group's Cystic Fibrosis Trials Register using the term 'inspiratory muscle training'.

The Group's Cystic Fibrosis Trials Register, which is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of The Cochrane Library), quarterly searches of MEDLINE, a search of Embase to 1995 and the prospective handsearching of two journals - Pediatric Pulmonology and the Journal of Cystic Fibrosis. Unpublished work is identified by searching the abstract books of four major cystic fibrosis conferences: the International Cystic Fibrosis Conference; the European Cystic Fibrosis Conference, the North American Cystic Fibrosis Conference and the Australia and New Zealand Cystic Fibrosis Conference. For full details of all searching activities for the register, please see the relevant sections of the Cystic Fibrosis and Genetic Disorders Group Module. Date of the last search of the Group's Cystic Fibrosis Trials Register: 08 July 2013.

We also performed separate searches of the following databases: MEDLINE, Embase, CINAHL, AMED (Allied and Complementary Medicine), PEDro (The Physiotherapy Evidence Database), BIOSIS Previews, Science Direct and SCOPUS to 2013, using both the Cochrane RCT and Cystic Fibrosis search filters; and terms specific to the intervention (Appendix 1; Appendix 2; Appendix 3; Appendix 4). We also searched Current Controlled Trials and the UK National Research Register for ongoing and recently completed studies. These searches were updated and run again on the 01 August 2013 (Appendix 3; Appendix 4; Appendix 5).

Searching other resources

For the original review, we also contacted manufacturers and study investigators and checked reference lists of relevant literature.

Data collection and analysis

Selection of studies

All three authors screened the output of electronic searches (title and abstract) to identify potentially eligible studies. From the full reports, all three authors independently selected studies for inclusion into the review. We planned to resolve any disagreements by discussion and if necessary by arbitration from a third person (Helen Handoll); however, this was not necessary.

Data extraction and management

All three authors independently collected data using standardised forms made available by the Cystic Fibrosis and Genetic Disorders Group. The authors did not need to resolve any disagreements.

Assessment of risk of bias in included studies

In order to assess the risk of bias, using a standardised form, all three authors independently assessed study quality according to the following criteria from the Cochrane risk of bias tool (Higgins 2011a): sequence generation; allocation concealment; the degree of blinding; whether incomplete data was included in the analysis (i.e. the intention-to-treat principle); whether there was selective reporting of results and any other identified sources of bias. We also commented on aspects of external validity, in particular the description of study participants and study interventions (e.g. in resistive IMT, has inspiratory flow rate been specifically controlled or not?), and the reliability of outcome assessment (including any reporting of the participants' 'familiarity' with the intended method of assessment), especially length of follow up. We reported on whether the included studies used systematic methods to record adverse events. We planned to resolve any disagreements by discussion and if necessary by arbitration from a third person (Helen Handoll); however, this was not necessary.

Measures of treatment effect

We have graphically presented quantitative data for the outcomes listed in the inclusion criteria. For each study, we planned to calculate risk ratios (RR) and 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MD) and 95% CIs for continuous outcomes.

Unit of analysis issues

Ideally when conducting a meta-analysis combining results from cross-over studies, we will use the inverse variance methods that are recommended by Elbourne (Elbourne 2002). However, if there are limited data available we planned to either use first arm data only or treat the cross-over trial as if it was a parallel trial (assuming a correlation of zero as the most conservative estimate). Elbourne says that this approach produces conservative results as it does not take into account within-patient correlation (Elbourne 2002). Also each participant appears in both the treatment and control group, so the two groups are not independent. There was one cross-over trial included in the review. Currently we have reported results from this trial narratively but for the first update of this review we plan to analyse this using the generic inverse variance (GIV) method. At which point, if we need to combine data from cross-over studies in a meta-analysis with data from parallel studies, we will use the methods discussed by Curtin (Curtin 2002a; Curtin 2002b; Curtin 2002c).

Where studies measured data longitudinally, the authors based the analysis on the final time point results. Methods are not yet available to carry out a meta-analysis of aggregate longitudinal data, where individual patient data (IPD) is not available.

Dealing with missing data

We contacted the authors of some of the studies in order to obtain more specific data to that presented; e.g. means and standard deviations; however, we have received no response to date.

Assessment of heterogeneity

If sufficient studies (at least four) had been included which we were able to combine in a meta-analysis, we planned to test for heterogeneity between comparable studies using a standard chi² test and to consider this statistically significant at P < 0.1. In addition we planned to use the value of the I² statistic to assist in determining levels of heterogeneity (Higgins 2003). We planned to base our judgements on the convention that 0 to 40% is unlikely to be important, 30 to 60% could be indicative of moderate heterogeneity, 50 to 90% may indicate important levels of heterogeneity and 75 to 100% suggests considerable heterogeneity (Higgins 2011b).

Assessment of reporting biases

If sufficient data were available, we planned to attempt to assess publication bias by preparing a funnel plot.

Data synthesis

We planned to pool the results of comparable groups of studies using the fixed-effect model and calculate 95% CIs.

Subgroup analysis and investigation of heterogeneity

We would not perform meta-analysis if we considered it would be misleading to quote an average value for the treatment effect, such as where there is substantial and statistically significant heterogeneity. As pooling of data from the included studies is inappropriate or not possible due variations in the level of IMT employed, we have provided appropriate narrative descriptions of the results. However, we have included graphical representation of some of the extracted data, which may be added to in the future (see Data and analyses).

Should there have been significant heterogeneity and if there had been a sufficient number of included studies, we would have explored the possible causes of the heterogeneity using subgroup analysis in terms of the following parameters:

  1. type of IMT (e.g. low level versus high level);

  2. regimen of IMT (e.g. daily versus three times per week);

  3. characteristics of study participants

    1. age (up to 16 years versus older than 16 years);

    2. gender of study participants;

    3. genotype;

    4. participants with 'weak' inspiratory muscles strength compared to those with preserved strength (as determined by PImax);

    5. participants with mild hyperinflation to those with severe hyperinflation (as determined by their total lung capacity (TLC)) or mixed populations with comparable interventions.

  4. definition of outcome measures.

Sensitivity analysis

If sufficient studies had been included, we planned to perform sensitivity analyses exploring the effects of published and unpublished studies, allocation concealment, assessor blinding and loss to follow up. We planned to conduct best-case and worst-case scenario plots to investigate the potential effects of loss to follow up.

Results

Description of studies

Results of the search

The results of the first stage of the search are given below.

  • The Cystic Fibrosis and Genetic Disorders Group's CF Trials Register provided 15 citations for 10 studies all of which were considered as potentially eligible for inclusion.

  • A search of EBSCOhost databases (OVID for the original review), MEDLINE, Embase, CINAHL, BIOSIS Previews and AMED (Allied and Complementary Medicine) returned 188 potential studies, of which, 14 were considered as eligible for potential inclusion.

  • A search of PEDro (The Physiotherapy Evidence Database) returned 73 potential studies, of which, 12 were considered for potential inclusion.

  • A search of Science Direct and SCOPUS did not produce any studies not already identified by the above searches.

All three authors reviewed the abstracts of the returned studies and selected those relevant to the scope of this review. This process left us with a final pool of 14 studies. From these 14, eight studies with a total of 180 participants were included (Albinni 2004; Amelina 2006; Asher 1983; Chatham 1997; de Jong 2001; Enright 2004; Heward 2000; Sawyer 1993) and six were excluded (Howard 2000; Irons 2012 ; Keens 1977; Santana-Sosa 2013 ; Sartori 2008 ; Vivodtzev 2013). Of the eight included studies, four were published as abstracts only (Albinni 2004; Amelina 2006; Chatham 1997; Heward 2000).

Included studies

A full comparison of the included studies can be found in the table Characteristics of included studies.

Trial design

Of the eight included studies, seven were of a parallel design; i.e. a control and an experimental group participating in the study concurrently (Albinni 2004; Amelina 2006; Chatham 1997; de Jong 2001; Enright 2004; Heward 2000; Sawyer 1993) with one of these having three arms to the study, i.e. a control and two levels of training (Enright 2004). One was of a cross-over design; i.e. the participants were randomly allocated to receive the training first or second (Asher 1983); we appreciate that these data would best be analysed in RevMan using the generic inverse variance (GIV) method; however, the trial authors did not supply the parameters required for this analysis.

The duration of the intervention ranged from four (Asher 1983) to 12 weeks (Albinni 2004) and all outcomes were recorded at the end of the trial period in each case.

The studies were run in a number of different countries: the USA (Heward 2000; Sawyer 1993); the UK (Chatham 1997; Enright 2004); the Netherlands (de Jong 2001); Canada (Asher 1983); Russia (Amelina 2006); and Austria (Albinni 2004). While most were single centre studies (Albinni 2004; Amelina 2006; de Jong 2001; Enright 2004; Sawyer 1993), it was unclear in three studies if they were single or multicentre (Asher 1983; Chatham 1997; Heward 2000).

All studies were relatively small with the number of participants ranging from 11 (Asher 1983) to 29 (Enright 2004).

Participants

Participant characteristics were not consistently reported across studies. Two studies did not give any indication of the exact mean age or age range of participants, but indicated that they were adults (Amelina 2006; Chatham 1997). One further study explicitly stated that participants were adults and gave a mean age of 22.5 years (Heward 2000). Two studies reported age ranges that included children, adolescents and young adults; 6 to 18 years (Albinni 2004) and 9 to 24 years (Asher 1983). The remaining three studies gave more detailed information on patient age and indeed split according to treatment group (de Jong 2001; Enright 2004; Sawyer 1993). In each study ages were similar between groups, but while the mean age for participants in two groups was in the early 20s (de Jong 2001; Enright 2004), in one study it indicated that participants were children and adolescents (Sawyer 1993).

Six of the studies did not report on the gender split in participants (Albinni 2004; Amelina 2006; Asher 1983; Chatham 1997; Heward 2000; Sawyer 1993). Two studies reported on gender split by treatment group; in one study there were equal numbers of males and females (de Jong 2001) and in the second there were slightly more males than females (Enright 2004).

Interventions

There was great variation as to the method and level of training employed by the included studies; e.g. IMT as a percentage of maximum effort or by threshold loading. Three studies used 80% compared to 20% of maximal effort (Chatham 1997; Enright 2004; Heward 2000); one study used 60% of maximal effort (Sawyer 1993); one study used 40% of maximal effort (de Jong 2001); one study used 30% of maximal effort (Amelina 2006) and two studies did not specify the level of resistance (Albinni 2004; Asher 1983). The frequency of training also varied. In two studies the frequency and duration of training was unclear (Chatham 1997; Heward 2000). Three studies used similar training regimens (Amelina 2006; Asher 1983; Sawyer 1993); of these one recommended a duration for each session of 10 to 15 minutes twice daily (Amelina 2006), of 15 minutes twice daily (Asher 1983) and 30 minutes in total daily (Sawyer 1993). The remaining two studies used a regimen of training three times per week, but the duration of the sessions either varied (Enright 2004) or was not stated (Albinni 2004).

Outcomes

The outcome measures selected by the studies also varied greatly. All studies reported some measure of inspiratory or respiratory muscle strength. Most studies reported at least one measure of lung function; the most common of these were FEV1 (Albinni 2004; Amelina 2006; de Jong 2001; Enright 2004; Sawyer 1993) and FVC (Albinni 2004; Amelina 2006; de Jong 2001; Enright 2004). Two studies used the Chronic Respiratory Disease Questionnaire to report QoL (Chatham 1997; Enright 2004), but other studies also reported on similar outcomes such as perceived breathlessness (Albinni 2004; de Jong 2001) and fatigue (de Jong 2001).

Excluded studies

One study was excluded from the original search as the allocation was not randomised (Keens 1977); likewise a study identified in the 2011 update was excluded as the allocation was not randomised (observational study) (Sartori 2008). A further study was identified and excluded from the 2011 update as the intervention was not appropriate (Howard 2000); likewise two studies identified in the 2013 update were excluded as the interventions were not appropriate (Irons 2012; Vivodtzev 2013). Although a form of IMT was used as an intervention in the remaining study, it was used in combination with another exercise based intervention; therefore, it was impossible to attribute any observed changes to IMT alone. As such, the study was excluded (Santana-Sosa 2013) (see Characteristics of excluded studies).

Risk of bias in included studies

Allocation

Generation of allocation sequence

Although eight of the studies state that they randomised their participants to the treatment groups, only one study offers any indication of the methods of allocation by stating that they employed the minimisation method (de Jong 2001). We graded this study as having a low risk of bias, but the remaining seven studies were graded as having an unclear risk of bias.

Concealment of allocation sequence

None of the included studies made specific reference as to how, or even whether, this was addressed. All studies were assessed as having an unclear risk of bias in relation to this criteria.

Blinding

Performance bias

We have scored all the included studies as having a high risk of bias in this parameter. In all studies there was clear difference between the experimental and control training; ranging from no details being provided for the control group (Asher 1983) and "no IMT training" (Albinni 2004; Enright 2004; Heward 2000) through to minimal training and "sham" training (Amelina 2006; Chatham 1997; de Jong 2001; Sawyer 1993). Although we acknowledge the methodological difficulties of blinding the participants to this type of intervention, it would have been straight forward to survey the participants at the end of data collection to establish whether they could tell if they received the training dose or not.

Dectection bias

Two studies blinded the outcome assessors at the final data collection session, although they did not state whether this was the case at the initial assessment or even if the same assessors carried out all the assessments (Enright 2004; Sawyer 1993). Another study reports that the observers were blinded, although it does not expand on the level of this (Asher 1983). The other five studies make no overt reference to any blinding (Albinni 2004; Amelina 2006; Chatham 1997; de Jong 2001; Heward 2000).

Incomplete outcome data

No study explicitly refers to intention-to-treat. However, five studies do report withdrawals. In the de Jong study, one participant in the intervention group withdrew after experiencing earache at 40% PImax training intensity (de Jong 2001). In the Asher study, two participants did not perform one of the post-treatment outcome measures, namely PIMax, due to expiration up to residual volume resulting in coughing (Asher 1983). In the Sawyer study two participants did not complete their pulmonary function tests: one was due to an oversight on the part of the researchers; and the other did not complete the test (Sawyer 1993). There is no indication as to which group these participants are from (Sawyer 1993). We consider that, for all three studies, these withdrawals relate to the true outcome and therefore introduce a high risk of bias.

In the Chatham study, three participants in the control group did not complete the trial (Chatham 1997); and in the Amelina study, one participant in the intervention group did not complete the trial (Amelina 2006). Neither of these last two studies offered any explanation for these withdrawals. As they are both abstracts we have graded them as 'unclear' on the grounds that they had limited space in which to explain the omissions. The two trials added during the update to this review did not provide statistical data on their control groups, merely stating that there was no change in their outcomes (Amelina 2006; Chatham 1997). We do acknowledge, however, that these were both abstracts published in conference proceedings and that there are likely to be editorial constraints responsible for this. Therefore, they are regarded as having an 'unclear' risk of bias.

The remaining three trials do not provide any information with regards to participant withdrawals, so we judge these to have an unclear risk of bias (Albinni 2004; Enright 2004; Heward 2000).

Selective reporting

One study mentions that the investigators carried out post-training measures of pulmonary function but do not report the results (Heward 2000). It is acknowledged that this study is only published as an abstract; however, there is a potential risk of bias due to the limited reporting of their outcomes. Likewise for the study by Amelina, two outcomes (respiratory muscle strength and dyspnoea) are mentioned as having been analysed, but no data are provided for them (Amelina 2006).

There was insufficient information provided by the other publications to make a judgement on the risk of bias due to selective reporting from six trials and we judge these to have an unclear risk of bias (Albinni 2004; Asher 1983; Chatham 1997; de Jong 2001; Enright 2004; Sawyer 1993).

Other potential sources of bias

We have given all the included studies a grading of 'unclear' risk of bias as none provided sufficient information to arrive at a definitive conclusion.

Effects of interventions

Due to the lack of studies using identical intensities of IMT or outcome measures, or both, it continues to be impossible, at this time, to pool any of the data; we have deemed it inappropriate to combine the data from the included trials. Please note that all outcomes were recorded at the end of the study period in each study.

Primary outcomes

1. Health-related quality of life

Two of the studies included in the review reported having used an outcome measure of this type. Both used the Chronic Respiratory Disease Questionnaire (CRDQ), which evaluates four domains considered important to individuals with chronic airflow obstruction; dyspnoea, mastery, fatigue and emotion (Enright 2004; Chatham 1997).

i. 80% of maximal effort

One study reported significant improvement in the two parameters of mastery and emotion (P < 0.01) (Chatham 1997). No statistically significant change was reported in the other paper for any of the four categories (Enright 2004).

ii. 60% of maximal effort

The Sawyer study did not report on this outcome (Sawyer 1993).

iii. 40% of maximal effort

The de Jong study did not report on this outcome (de Jong 2001).

iv. 20% of maximal effort

No statistically significant change was reported in the paper for any of these four categories (Enright 2004).

v. unspecified level of maximal effort

The Asher and Albinni studies did not report on this outcome (Albinni 2004; Asher 1983).

2. Pulmonary function tests (performed at rest)
a. Forced expiratory volume at one second (FEV1)

Data for FEV1 were reported in six of the included studies (Albinni 2004; Amelina 2006; Asher 1983; de Jong 2001; Enright 2004; Sawyer 1993). One study stated that post-training measures of pulmonary function were determined, but did not report any further details (Heward 2000); and the remaining study did not mention this outcome (Chatham 1997).

i. 80% of maximal effort

Enright reported mean and SD data for all groups and reported no significant difference between all three of their groups (two intensities of IMT (see also 20% of maximal effort below) and a control) (Enright 2004).

ii. 60% of maximal effort

The Sawyer study presented FEV1 in litres and reported a P value indicating no difference between IMT and control (P = 0.10) (Sawyer 1993).

iii. 40% of maximal effort

The de Jong study presents FEV1 in litres and reports a P value indicating no difference between IMT and control (P = 0.82) (de Jong 2001).

iv. 30% of maximal effort

The Amelina study presented FEV1 in per cent predicted and reports a mean improvement within the training group from 48% to 51% with a P value of 0.014 (Amelina 2006).

v. 20% of maximal effort

Enright reported mean and SD data for this group, but did not report any significant difference between IMT and control (Enright 2004).

vi. unspecified level of maximal effort

The Asher and Albinni studies did not report any data, but state that there was no change in FEV1 in either the IMT or the control group (Albinni 2004; Asher 1983).

b. Forced vital capacity (FVC)

This outcome is reported in three studies (Albinni 2004; de Jong 2001; Enright 2004); all using the same unit of measurement (litres).

i. 80% of maximal effort

Enright presented mean and standard deviations for all groups, pre- and post-IMT and these figures have been presented in the graphs. There were no reported statistically significant changes following the training (Enright 2004). Chatham did not report on this outcome (Chatham 1997).

ii. 60% of maximal effort

This outcome was not reported by Sawyer (Sawyer 1993).

iii. 40% of maximal effort

The de Jong study quoted mean and standard deviations for all groups, pre- and post-IMT and these figures have been presented in the graphs. There were no reported statistically significant changes following the training, but de Jong did report the actual level of significance (P = 0.99) (de Jong 2001).

iv. 30% of maximal effort

The Amelina study presented FVC in per cent predicted and reports a mean improvement within the training group from 65% to 68% with a P value of 0.049 (Amelina 2006).

v. 20% of maximal effort

Enright presented mean and standard deviations for all groups, pre- and post-IMT and these figures have been presented in the graphs. There were no reported statistically significant changes following the training (Enright 2004).

vi. unspecified level of maximal effort

Albini stated there was no change in FVC in either group, but gave no further details (Albinni 2004). This outcome was not reported by Asher (Albinni 2004; Asher 1983).

3. Exercise tolerance
a. Field-based tests

No studies reported this outcome.

b. Laboratory-based tests

Three studies reported VO2max (Albinni 2004; Asher 1983; de Jong 2001).

i. 80% of maximal effort

Neither study reported on this outcome (Chatham 1997; Enright 2004).

ii. 60% of maximal effort

This outcome was not reported by Sawyer (Sawyer 1993).

iii. 40% of maximal effort

The de Jong study reported no statistically significant change in VO2 max (P = 0.99) (de Jong 2001).

iv. 20% of maximal effort

Enright did not report this outcome (Enright 2004).

v. unspecified level of maximal effort

One study reported a significant improvement in VO2max within the IMT group (P = 0.01) (Albinni 2004); although no data were reported to allow inclusion in our analysis. A second study reported pre- and post-intervention mean scores but no statistical analysis, although they did state that no difference was detected between the groups (Asher 1983).

One study reported on "exercise capacity" although no units were provided not was there any explanation as to the method of assessment; they reported no improvement in this outcome (Amelina 2006).

Secondary outcomes

1. Pulmonary function tests (performed at rest)
a. Maximal inspiratory pressure (PImax)
i. 80% of maximal effort

Neither study reported on this outcome (Chatham 1997; Enright 2004).

ii. 60% of maximal effort

When the data for this outcome from the Sawyer study are entered into the analysis there is a significant difference in favour of the treatment group, MD 26.00 (95% CI 8.63 to 43.47) (Sawyer 1993) (Analysis 2.2).

iii. 40% of maximal effort

The de Jong study did not report on this outcome (de Jong 2001).

iv. 30% of maximal effort

The Amelina study presented PImax in per cent predicted and reports a mean improvement within the training group from 77% to 91% with a P value of 0.023 (Amelina 2006).

v. 20% of maximal effort

The Enright study did not report on this outcome (Enright 2004).

vi. unspecified level of maximal effort

Asher utilised two inspiratory measures (Pim-FRC and PImax) suggesting that one measurement technique was used but at two different lung volumes (Asher 1983). The study reported significant changes in both measures in the IMT group (P < 0.025 and P < 0.05 respectively). The investigators also reported that, for the Pim-FRC measure, only three participants registered an increase that was more than two standard deviations (2SD) from the control group; and for the PImax measure, two participants had an increase greater than two SD from the control values.

b. Inspiratory capacity (IC)

This outcome was not reported by any study.

2. Respiratory muscle function (strength and endurance)

Inspiratory muscle endurance (IME) was reported in two studies (Albinni 2004; de Jong 2001).

i. 80% of maximal effort

The Chatham study reported figures for mean (SD) and a P value for the training group only; therefore, they have not been included in our analysis. There was a mean improvement within the training group from 118 (31.5) to 149 (24.7) mmH2O with a P value of less than 0.04 (Chatham 1997). Enright did not report this outcome (Enright 2004).

ii. 60% of maximal effort

This outcome was not reported by Sawyer (Sawyer 1993).

iii. 40% of maximal effort

The de Jong study quoted figures for mean, standard deviation and P value and has therefore been included in our analysis. There was a statistically significant difference in favour of the IMT group, MD 12.00 (95% CI 0.55 to 23.45) (de Jong 2001) (Analysis 3.5).

iv. 30% of maximal effort

The Amelina study reported this outcome in joules (J) and reports a mean improvement within the training group from 89J to 150J with a P value of 0.002 (Amelina 2006).

v. 20% of maximal effort

Enright did not report this outcome (Enright 2004).

vi. unspecified level of maximal effort

Albinni reported that IME improved significantly in the training group (P= 0.0002) (Albinni 2004).

3. Frequency and duration of respiratory infections, hospitalisations

This outcome was not reported by any study.

4. Adherence to the IMT regimen

This outcome was not reported by any study.

5. Death or survival

No deaths were reported and survival was not analysed in any study.

6. Adverse effects (pneumothorax, musculoskeletal pains or injuries, others)

One study, using 40% of maximal effort, reported that one participant experienced earache whilst performing IMT (de Jong 2001).

7. Costs

This outcome was not reported by any study.

Discussion

Overall the quality of the included studies was inconsistent and none addressed all aspects completely. The execution of the included studies (randomisation and blinding) ranged from being fully acknowledged, considered and reported to either being merely stated as "randomised to the two groups" or not being mentioned. The external validity (with particular regard to the participant demographics) was explicit in only three of the studies (de Jong 2001; Enright 2004; Sawyer 1993). This aspect is of particular significance given that people who have CF are the target population. The nature of the disease means that two people of similar age, height and weight may have been affected by the condition in drastically different ways and therefore may not "match" as far as clinical status goes. Adverse events were poorly covered by the studies, with only one making specific reference to this (de Jong 2001). Two studies report withdrawals but offer no explanation for these (Amelina 2006; Chatham 1997). We acknowledge that the nature of the intervention (IMT) makes it very difficult to blind the participants to which arm they are in, although five studies made use of "sham" interventions for controls (Amelina 2006; Chatham 1997; de Jong 2001; Enright 2004; Sawyer 1993).

There is currently insufficient evidence to either support or refute the use of IMT for people with CF (Altman 1995). There are several factors that may have contributed to this conclusion. Firstly, four out of the eight studies have only been published as abstracts within conference proceedings. This format limits the amount of detailed data that are presented and, therefore, that can be extracted from the studies. This is particularly true in this case. Without that detail a full meta-analysis cannot be performed and this subsequently detracts from the rigour of the process. Another, more generic, factor relates to the execution of studies examining the effects of a rehabilitation technique for people with CF. A systematic review requires homogeneity between the included studies to allow firm conclusions to be drawn. Despite only finding eight studies which met the inclusion criteria of this review, the variation in their methodologies and outcomes (type and units) was such that no combined analyses could be made. These differences occurred in all the major aspects of the studies, i.e. the outcomes employed, the selected units of measurement for certain of these outcomes and the method and extent to which the clinical status of the participants was established or reported.

Two pulmonary function measures, FEV1 and FVC, are both routinely used in general clinical practice to monitor the pulmonary function and (due to the nature of the condition) the disease severity within people with CF. It could be argued that expiratory measures such as these would not be altered by an inspiratory intervention. We, however, support the studies' use of expiratory measures, primarily, because of their routine clinical usage and relevance in monitoring the progression of the disease. In selecting task specific measures some studies are opting for ones that specifically assess changes within the muscles of ventilation, e.g. diaphragm thickness. The problem with this is that they are not measures with which people with CF, or even the average professional working in the field, would be sufficiently familiar in order to be able to draw any meaningful conclusions. It would appear, even from this small sample, that this dilemma continues and needs resolving. Descriptive analysis of the studies considered suggests that the measures that can best detect the effects of an IMT programme are PImax exercise tests such as inspiratory muscle endurance and, to a lesser extent, VO2max. Although it is acknowledged that this is not supported by a meta-analysis of trials, they are the measures the included studies report as showing significant improvement within their IMT groups. Also, these are measures that are of particular relevance to professionals involved in the rehabilitation of people with CF and ones that are most likely to influence quality of life.

Only two of the studies included in the review reported having used an outcome measure assessing health-related quality of life (Chatham 1997; Enright 2004). We believe that this is a major omission on the part of the other studies, which severely limits the external validity of the research base. There is an ever growing drive to consider the efficacy of our interventions, as McClarey and Duff summarise, in the UK it is being driven centrally from the UK National Health Service (UK NHS) (McClarey 1997). What McClarey and Duff fail to fully acknowledge is that efficacy cannot be fully established without thorough assessment of how people with a particular condition perceive the benefits of their treatment (McClarey 1997). This ought to be of particular importance in long-term life-limiting conditions, such as CF. It is acknowledged, however, that certain of the studies may have been undertaken at a time before this became such an important consideration within clinical practice.

Due to the life-limiting nature of CF, the clinical status of the participants recruited to studies in this population is of particular importance. The participants from the included studies have a mean age of approximately 18.5 years. With average life expectancy around 31 years (CF Trust 2007), the participants in these studies are effectively in middle age. It is possible that due to the progressive nature of the condition, the pulmonary function of the participants prevented the benefits shown in healthy populations manifesting in this participant group (Enright 2000).

Authors' conclusions

Implications for practice

Given that we have not found any evidence to suggest that this treatment is either beneficial or not. We would advise that practitioners evaluate on a case-by-case basis whether or not to employ this therapy.

Implications for research

We recommend that future studies choose task specific measures such as PImax and inspiratory muscle strength and endurance as well as exercise tests such as VO2max. Such functional measures ought to dovetail nicely with an assessment of health-related quality of life.

To facilitate such future research and to improve research into the remedial benefits of IMT, it is necessary for the research community to agree upon a single standard measure of classifying the clinical status of the participants.

Finally, there is emerging evidence to suggest that IMT is beneficial to people with other chronic respiratory conditions, such as COPD (O'Brien 2008). It would be prudent to apply this to the clinical population and implement longitudinal studies to assess the role of IMT in maintaining good pulmonary function and exercise tolerance within the CF population.

Acknowledgements

We acknowledge the valuable contribution to the protocol stage of this review from Professor Cees van der Schans before he stepped down from the review team.

We thank the following for their help and advice at both the protocol and review stage: Mark Elkins, Helen Handoll, Kylie Hill, Nikki Jahnke, Ashley Jones, Heather McIntosh, Vicki Whittaker, Dr Gerard Ryan (editor) and Dr Harold Soloff (consumer referee).

Data and analyses

Download statistical data

Comparison 1. IMT (80% of maximal effort) versus control
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Forced expiratory volume at one second (litres)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Two to six months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Forced vital capacity (litres)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Two to six months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Chronic Respiratory Disease Questionnaire (mastery)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4 Chronic Respiratory Disease Questionnaire (emotion)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 IMT (80% of maximal effort) versus control, Outcome 1 Forced expiratory volume at one second (litres).

Analysis 1.2.

Comparison 1 IMT (80% of maximal effort) versus control, Outcome 2 Forced vital capacity (litres).

Analysis 1.3.

Comparison 1 IMT (80% of maximal effort) versus control, Outcome 3 Chronic Respiratory Disease Questionnaire (mastery).

Analysis 1.4.

Comparison 1 IMT (80% of maximal effort) versus control, Outcome 4 Chronic Respiratory Disease Questionnaire (emotion).

Comparison 2. IMT (60% of maximal effort) versus control
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Forced expiratory volume at one second (litres)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Two to six months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 PImax (cmH2O)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Two to six months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 2.1.

Comparison 2 IMT (60% of maximal effort) versus control, Outcome 1 Forced expiratory volume at one second (litres).

Analysis 2.2.

Comparison 2 IMT (60% of maximal effort) versus control, Outcome 2 PImax (cmH2O).

Comparison 3. IMT (40% of maximal effort) versus control
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Forced expiratory volume at one second (litres)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Less than two months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Forced expiratory volume at one second (% predicted)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Less than two months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Forced vital capacity (litres)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Less than two months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Forced vital capacity (% predicted)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4.1 Less than two months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Inspiratory muscle endurance (%PImax)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
5.1 Less than two months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 3.1.

Comparison 3 IMT (40% of maximal effort) versus control, Outcome 1 Forced expiratory volume at one second (litres).

Analysis 3.2.

Comparison 3 IMT (40% of maximal effort) versus control, Outcome 2 Forced expiratory volume at one second (% predicted).

Analysis 3.3.

Comparison 3 IMT (40% of maximal effort) versus control, Outcome 3 Forced vital capacity (litres).

Analysis 3.4.

Comparison 3 IMT (40% of maximal effort) versus control, Outcome 4 Forced vital capacity (% predicted).

Analysis 3.5.

Comparison 3 IMT (40% of maximal effort) versus control, Outcome 5 Inspiratory muscle endurance (%PImax).

Comparison 4. IMT (20% of maximal effort) versus control
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Forced expiratory volume at one second (litres)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Two to six months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Forced expiratory volume at one second (% predicted)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Two to six months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Forced vital capacity (litres)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Two to six months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 4.1.

Comparison 4 IMT (20% of maximal effort) versus control, Outcome 1 Forced expiratory volume at one second (litres).

Analysis 4.2.

Comparison 4 IMT (20% of maximal effort) versus control, Outcome 2 Forced expiratory volume at one second (% predicted).

Analysis 4.3.

Comparison 4 IMT (20% of maximal effort) versus control, Outcome 3 Forced vital capacity (litres).

Appendices

Appendix 1. Search strategy: MEDLINE, Embase, CINAHL, AMED, BIOSIS, EMB reviews (OVID-WEB)

Date of Search01/08/2013
Years Covered1966 to present
Complete Strategy1. randomised controlled trial.pt.
2. controlled clinical trial.pt.
3. randomised controlled trials.sh.
4. random allocation.sh.
5. double blind method.sh.
6. single blind method.sh.
7. or/1-6
8. (animals not human).sh.
9. 7 not 8
10. clinical trial.pt.
11. exp clinical trials/
12. (clin$ adj25 trial$).ti,ab.
13. ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab.
14. placebos.sh.
15. placebo$.ti,ab.
16. random$.ti,ab.
17. research design.sh.
18. or/10-17
19. 18 not 8
20. 19 not 9
21. comparative study.sh.
22. exp evaluation studies/
23. follow up studies.sh.
24. prospective studies.sh.
25. (control$ or prospectiv$ or volunteer$).ti,ab.
26. or/21-25
27. 26 not 8
28. 27 not (9 or 20)
29. 9 or 20 or 28
30. exp cystic fibrosis/
31. cystic fibrosis.mp.
32. (fibrocystic adj3 disease adj3 pancreas).tw.
33. mucoviscidos$.mp.
34. (cystic$ adj10 fibros$).tw.
35. (pancreatic adj3 cystic adj3 fibrosis).mp.
36. or/30-35
37. 29 and 36
38. ((train$ or cond$) adj25 (inspirator$ or ventilator$ or respirator$ or pulmonar$)).mp.
39. (voluntar$ adj3 isocapn$ adj3 hyperpnoe$).tw.
40. (resist$ adj3 load$).tw.
41. (pressu$ adj3 thresh$ adj3 load$).tw.
42. (elas$ adj3 load$).tw.
43. (incre$ adj3 thresh$ adj3 load$).tw.
44. or/38-43
45. 44 not 8
46. 45 and 37
47. remove duplicates from 46
Summary of StrategyLines 1 & 29 are the Cochrane RCT filter.
Lines 30 to 37 are the Cochrane cystic fibrosis filter.
Lines 38 to 45 were to isolate the intervention of interest.
The remainder were to combine these three themes.
Language RestrictionsNone

Appendix 2. Search strategy: PEDro

Date of search01/08/2013
Years covered1929 to present
Complete strategy1. inspir* mus* train*
2. resp* mus* train*
3. resp* mus* cond*
4. resist* load*
5. press* thresh* load*
6. incre* thresh* load*
7. cystic fibrosis
8. cyst* fibro*
9. pancreatic cystic fibrosis
Summary of strategyPEDro is a database of controlled clinical trials, therefore no specific design oriented search terms.
All terms were geared to isolate the condition and the intervention.
The returned citations were then manually combined to be specific to the review question.
Language restrictionsNone

Appendix 3. Search strategy: Science Direct

Date of search01/08/2013
Years covered1823 to present
Complete strategy1: (Title-Abstr-Key (random*)) OR (Title-Abstr-Key (placebo*)) OR (Title-Abstr-Key ((singl* or doubl* or trebl* or tripl*) w/25 (blind* or mask*))) OR (Title-Abstr-Key (clin* w/25 trial*))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
2: ((Title-Abstr-Key (random*)) OR (Title-Abstr-Key (placebo*)) OR (Title-Abstr-Key ((singl* or doubl* or trebl* or tripl*) w/25 (blind* or mask*))) OR (Title-Abstr-Key (clin* w/25 trial*))) OR ((Title-Abstr-Key (single blind method)) OR (Title-Abstr-Key (double blind method)) OR (Title-Abstr-Key (random allocation)) OR (Title-Abstr-Key (controlled clinical trial)) OR (Title-Abstr-Key (randomised controlled trial)))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
3: Title-Abstr-Key (cystic fibrosis)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
4: Title-Abstr-Key (fibrocystic w/3 disease w/3 pancreas)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
5: Title-Abstr-Key (mucoviscidos*)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
6: Title-Abstr-Key (cystic* w/10 fibros*)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
7: Title-Abstr-Key (pancreatic w/3 cystic w/3 fibrosis)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
8: (Title-Abstr-Key (pancreatic w/3 cystic w/3 fibrosis)) OR (Title-Abstr-Key (cystic* w/10 fibros*)) OR (Title-Abstr-Key (mucoviscidos*)) OR (Title-Abstr-Key (fibrocystic w/3 disease w/3 pancreas)) OR (Title-Abstr-Key (cystic fibrosis))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
9: Title-Abstr-Key (train* or cond*) w/3 (inspirator* or ventilator* or respirator* or pulmonar*)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
10: Title-Abstr-Key (resist* w/3 load*)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
11: Title-Abstr-Key (inspiratory muscle training)
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
12: (Title-Abstr-Key (inspiratory muscle training)) OR (Title-Abstr-Key (resist* w/3 load*)) OR (Title-Abstr-Key (train* or cond*) w/3 (inspirator* or ventilator* or respirator* or pulmonar*))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
13: (Title-Abstr-Key (inspiratory muscle training)) OR (Title-Abstr-Key (resist* w/3 load*)) OR (Title-Abstr-Key (train* or cond*) w/3 (inspirator* or ventilator* or respirator* or pulmonar*))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
14: ((Title-Abstr-Key (inspiratory muscle training)) OR (Title-Abstr-Key (resist* w/3 load*)) OR (Title-Abstr-Key (train* or cond*) w/3 (inspirator* or ventilator* or respirator* or pulmonar*))) AND ((Title-Abstr-Key (pancreatic w/3 cystic w/3 fibrosis)) OR (Title-Abstr-Key (cystic* w/10 fibros*)) OR (Title-Abstr-Key (mucoviscidos*)) OR (Title-Abstr-Key (fibrocystic w/3 disease w/3 pancreas)) OR (Title-Abstr-Key (cystic fibrosis))) AND (((Title-Abstr-Key (random*)) OR (Title-Abstr-Key (placebo*)) OR (Title-Abstr-Key ((singl* or doubl* or trebl* or tripl*) w/25 (blind* or mask*))) OR (Title-Abstr-Key (clin* w/25 trial*))) OR ((Title-Abstr-Key (single blind method)) OR (Title-Abstr-Key (double blind method)) OR (Title-Abstr-Key (random allocation)) OR (Title-Abstr-Key (controlled clinical trial)) OR (Title-Abstr-Key (randomised controlled trial))))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
15: ((Title-Abstr-Key (pancreatic w/3 cystic w/3 fibrosis)) OR (Title-Abstr-Key (cystic* w/10 fibros*)) OR (Title-Abstr-Key (mucoviscidos*)) OR (Title-Abstr-Key (fibrocystic w/3 disease w/3 pancreas)) OR (Title-Abstr-Key (cystic fibrosis))) AND (((Title-Abstr-Key (random*)) OR (Title-Abstr-Key (placebo*)) OR (Title-Abstr-Key ((singl* or doubl* or trebl* or tripl*) w/25 (blind* or mask*))) OR (Title-Abstr-Key (clin* w/25 trial*))) OR ((Title-Abstr-Key (single blind method)) OR (Title-Abstr-Key (double blind method)) OR (Title-Abstr-Key (random allocation)) OR (Title-Abstr-Key (controlled clinical trial)) OR (Title-Abstr-Key (randomised controlled trial))))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
16: ((Title-Abstr-Key (inspiratory muscle training)) OR (Title-Abstr-Key (resist* w/3 load*)) OR (Title-Abstr-Key (train* or cond*) w/3 (inspirator* or ventilator* or respirator* or pulmonar*))) AND ((Title-Abstr-Key (pancreatic w/3 cystic w/3 fibrosis)) OR (Title-Abstr-Key (cystic* w/10 fibros*)) OR (Title-Abstr-Key (mucoviscidos*)) OR (Title-Abstr-Key (fibrocystic w/3 disease w/3 pancreas)) OR (Title-Abstr-Key (cystic fibrosis)))
[All Sources(Medicine and Dentistry,Nursing and Health Professions)]
Summary of strategyLines 1 & 2 were to isolate studies of appropriate design.
Lines 3 to 8 were to isolate the condition of interest.
Lines 9 to 13 were to isolate the intervention of interest.
The remainder were to combine these three themes.
Language restrictionsNone

Appendix 4. Search strategy: SCOPUS

Date of search01/08/2013
Years covered1966 to present
Complete strategy1: TITLE-ABS-KEY(randomised controlled trial)
2: TITLE-ABS-KEY(controlled clinical trial)
3: TITLE-ABS-KEY(random allocation)
4: TITLE-ABS-KEY(double blind method)
5: TITLE-ABS-KEY(single blind method)
6: TITLE-ABS-KEY(clin* W/25 trial*)
7: ((TITLE-ABS-KEY(randomised controlled trial)) OR (TITLE-ABS-KEY(controlled clinical trial)) OR (TITLE-ABS-KEY(random allocation)) OR (TITLE-ABS-KEY(double blind method)) OR (TITLE-ABS-KEY(single blind method))) OR (TITLE-ABS-KEY(clin* W/25 trial*))
8: INDEXTERMS(cystic fibrosis)
9: TITLE-ABS-KEY(fibrocystic W/3 disease W/3 pancreas)
10: TITLE-ABS-KEY(mucoviscidos*)
11: TITLE-ABS-KEY(cystic* W/10 fibros*)
12: TITLE-ABS-KEY(pancreatic W/3 cystic W/3 fibrosis)
13: (INDEXTERMS(cystic fibrosis)) OR (TITLE-ABS-KEY(fibrocystic W/3 disease W/3 pancreas)) OR (TITLE-ABS-KEY(mucoviscidos*)) OR (TITLE-ABS-KEY(cystic* W/10 fibros*)) OR (TITLE-ABS-KEY(pancreatic W/3 cystic W/3 fibrosis))
14: TITLE-ABS-KEY(respiratory muscle training)
15: TITLE-ABS-KEY(ventilatory muscle training)
16: TITLE-ABS-KEY(pulmonary muscle training)
17: TITLE-ABS-KEY(resist* W/3 load*)
18: TITLE-ABS-KEY(pressu* W/3 thresh* W/3 load*)
19: TITLE-ABS-KEY(elas* W/3 load*)
20: TITLE-ABS-KEY(incre* W/3 thresh* W/3 load*)
21: (TITLE-ABS-KEY(pressu* W/3 thresh* W/3 load*)) OR (TITLE-ABS-KEY(elas* W/3 load*)) OR (TITLE-ABS-KEY(incre* W/3 thresh* W/3 load*)) OR ((TITLE-ABS-KEY(inspiratory muscle training)) OR (TITLE-ABS-KEY(respiratory muscle training)) OR (TITLE-ABS-KEY(ventilatory muscle training)) OR (TITLE-ABS-KEY(pulmonary muscle training)) OR (TITLE-ABS-KEY(resist* W/3 load*)))
22: ((INDEXTERMS(cystic fibrosis)) OR (TITLE-ABS-KEY(fibrocystic W/3 disease W/3 pancreas)) OR (TITLE-ABS-KEY(mucoviscidos*)) OR (TITLE-ABS-KEY(cystic* W/10 fibros*)) OR (TITLE-ABS-KEY(pancreatic W/3 cystic W/3 fibrosis))) AND (((TITLE-ABS-KEY(randomised controlled trial)) OR (TITLE-ABS-KEY(controlled clinical trial)) OR (TITLE-ABS-KEY(random allocation)) OR (TITLE-ABS-KEY(double blind method)) OR (TITLE-ABS-KEY(single blind method))) OR (TITLE-ABS-KEY(clin* W/25 trial*))) AND ((TITLE-ABS-KEY(pressu* W/3 thresh* W/3 load*)) OR (TITLE-ABS-KEY(elas* W/3 load*)) OR (TITLE-ABS-KEY(incre* W/3 thresh* W/3 load*)) OR ((TITLE-ABS-KEY(inspiratory muscle traning)) OR (TITLE-ABS-KEY(respiratory muscle training)) OR (TITLE-ABS-KEY(ventilatory muscle training)) OR (TITLE-ABS-KEY(pulmonary muscle training)) OR (TITLE-ABS-KEY(resist* W/3 load*))))
Summary of strategyLines 1 to 7 were to isolate appropriate study design.
Lines 8 to 13 were to isolate the condition.
Lines 14 to 21 were to isolate the intervention.
Line 22: Combines these three themes.
Language restrictionsNone

Appendix 5. Search strategy: MEDLINE, CINHAL and AMED (EBSCOHost)

Date of search01/08/2013
Years covered1966 to present
Complete strategy1: TITLE-ABS-KEY(randomised controlled trial)
2: TITLE-ABS-KEY(controlled clinical trial)
3: TITLE-ABS-KEY(random allocation)
4: TITLE-ABS-KEY(double blind method)
5: TITLE-ABS-KEY(single blind method)
6: TITLE-ABS-KEY(clin* W/25 trial*)
7: ((TITLE-ABS-KEY(randomised controlled trial)) OR (TITLE-ABS-KEY(controlled clinical trial)) OR (TITLE-ABS-KEY(random allocation)) OR (TITLE-ABS-KEY(double blind method)) OR (TITLE-ABS-KEY(single blind method))) OR (TITLE-ABS-KEY(clin* W/25 trial*))
8: INDEXTERMS(cystic fibrosis)
9: TITLE-ABS-KEY(fibrocystic W/3 disease W/3 pancreas)
10: TITLE-ABS-KEY(mucoviscidos*)
11: TITLE-ABS-KEY(cystic* W/10 fibros*)
12: TITLE-ABS-KEY(pancreatic W/3 cystic W/3 fibrosis)
13: (INDEXTERMS(cystic fibrosis)) OR (TITLE-ABS-KEY(fibrocystic W/3 disease W/3 pancreas)) OR (TITLE-ABS-KEY(mucoviscidos*)) OR (TITLE-ABS-KEY(cystic* W/10 fibros*)) OR (TITLE-ABS-KEY(pancreatic W/3 cystic W/3 fibrosis))
14: TITLE-ABS-KEY(respiratory muscle training)
15: TITLE-ABS-KEY(ventilatory muscle training)
16: TITLE-ABS-KEY(pulmonary muscle training)
17: TITLE-ABS-KEY(resist* W/3 load*)
18: TITLE-ABS-KEY(pressu* W/3 thresh* W/3 load*)
19: TITLE-ABS-KEY(elas* W/3 load*)
20: TITLE-ABS-KEY(incre* W/3 thresh* W/3 load*)
21: (TITLE-ABS-KEY(pressu* W/3 thresh* W/3 load*)) OR (TITLE-ABS-KEY(elas* W/3 load*)) OR (TITLE-ABS-KEY(incre* W/3 thresh* W/3 load*)) OR ((TITLE-ABS-KEY(inspiratory muscle training)) OR (TITLE-ABS-KEY(respiratory muscle training)) OR (TITLE-ABS-KEY(ventilatory muscle training)) OR (TITLE-ABS-KEY(pulmonary muscle training)) OR (TITLE-ABS-KEY(resist* W/3 load*)))
22: ((INDEXTERMS(cystic fibrosis)) OR (TITLE-ABS-KEY(fibrocystic W/3 disease W/3 pancreas)) OR (TITLE-ABS-KEY(mucoviscidos*)) OR (TITLE-ABS-KEY(cystic* W/10 fibros*)) OR (TITLE-ABS-KEY(pancreatic W/3 cystic W/3 fibrosis))) AND (((TITLE-ABS-KEY(randomised controlled trial)) OR (TITLE-ABS-KEY(controlled clinical trial)) OR (TITLE-ABS-KEY(random allocation)) OR (TITLE-ABS-KEY(double blind method)) OR (TITLE-ABS-KEY(single blind method))) OR (TITLE-ABS-KEY(clin* W/25 trial*))) AND ((TITLE-ABS-KEY(pressu* W/3 thresh* W/3 load*)) OR (TITLE-ABS-KEY(elas* W/3 load*)) OR (TITLE-ABS-KEY(incre* W/3 thresh* W/3 load*)) OR ((TITLE-ABS-KEY(inspiratory muscle traning)) OR (TITLE-ABS-KEY(respiratory muscle training)) OR (TITLE-ABS-KEY(ventilatory muscle training)) OR (TITLE-ABS-KEY(pulmonary muscle training)) OR (TITLE-ABS-KEY(resist* W/3 load*))))
Summary of strategyLines 1 to 7 were to isolate appropriate study design.
Lines 8 to 13 were to isolate the condition.
Lines 14 to 21 were to isolate the intervention.
Line 22: Combines these three themes.
Language restrictionsNone

What's new

DateEventDescription
10 October 2013New search has been performedA search of the Cystic Fibrosis & Genetic Disorders Group's Cystic Fibrosis Register identified two references to a single study that was potentially eligible for inclusion in the review; this study has been excluded (Irons 2012). Searches of MEDLINE, CIHNAL, AMED and SCOPUS identified two additional studies that were potentially eligible for inclusion in the review, but both of these were also excluded (Santana-Sosa 2013; Vivodtzev 2013).
10 October 2013New citation required but conclusions have not changedNo new studies have been included in this update of the review and our conclusions have remained the same.

History

Protocol first published: Issue 3, 2006
Review first published: Issue 4, 2008

DateEventDescription
28 September 2011New search has been performed

A search of the Cystic Fibrosis Trials Register identified three new references which were potentially eligible for inclusion in this review (Amelina 2006; Chatham 1997; Howard 2000). Two studies were eligible for inclusion (Amelina 2006; Chatham 1997); the third study was excluded (Howard 2000).

Additional searching undertaken for the updated review identified one study that was potentially eligible for inclusion (Sartori 2008); however this was excluded on closer examination.

28 April 2008AmendedConverted to new review format.

Contributions of authors

Brian Houston drafted the protocol with comments from Helen Handoll and Cees van der Schans.

Nicola Mills, Arturo Solis-Moya and Brian Houston extracted data and assessed trial quality. Brian Houston drafted the full review with comments from Nicola Mills and Arturo Solis-Moya.

Brian Houston acts as guarantor of the review.

Declarations of interest

None known.

Sources of support

Internal sources

  • University of Teesside, Middlesbrough, UK.

External sources

  • No sources of support supplied

Differences between protocol and review

Update 2011
Due to Teesside University (location of the lead author) changing its search engine, some of the search strategies have been re-written. The search strategies in Appendix 5 have superseded those in Appendix 1.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Albinni 2004

MethodsParallel design over 12 weeks.
Single centre in Austria.
Participants

Total cohort: n = 27.

Age range: 6 - 18 years.

Gender mix: no information.

Interventions

IMT: no details; plus, cycle ergometer training 3 times per week.

Control: cycle ergometer training 3 times per week.

OutcomesFEV1, FVC, IMS, IME, MEC, perceived breathlessness, antibiotic use and ease or degree of expectoration.
NotesIME protocol: abstract only, no details given.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskDescribed as randomised, no details given.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
High risk

Performance bias: clear difference between the interventions received.

Dectection bias: No reference to any blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information provided. Intention-to-treat: unclear.
Selective reporting (reporting bias)Unclear riskInsufficient information available to arrive at a conclusion.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

Amelina 2006

Methods

Parallel design over 6 weeks.

Single centre in Russia.

Participants

Total cohort: n = 20. Treatment group: n = 10; control group: n = 10.

Age range was not stated, but all were adults.

Gender mix: no information.

States no significant differences between groups in terms of gender, age, weight, height, pulmonary function.

Interventions

Threshold loading device:

Intervention group: 30% of PImax

Control group: 7cm H2O

Training regimen: 10 to 15 minutes twice daily for 6 weeks.

OutcomesFEV1, FVC, PImax, IC, RMS, RME and exercise capacity.
NotesAbstract only.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskThe authors only state that the allocation was random without explaining the process involved.
Allocation concealment (selection bias)Unclear riskNo details are provided.
Blinding (performance bias and detection bias)
All outcomes
High risk

Performance bias: The comparison group are referred to only as the "control group" with no mention of the intensity of the training used; i.e. if it was at "sham" or sub-maximal levels.

Dectection bias: No reference to any blinding.

Incomplete outcome data (attrition bias)
All outcomes
High risk

No statistical data is presented for the control group.

1 participant from the intervention group did not complete the trial; it was not stated whether they were included or excluded from the final analysis.

Selective reporting (reporting bias)High risk2 outcomes (respiratory muscle strength and dyspnoea) are mentioned as having been analysed, but no data are provided for them.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

Asher 1983

Methods

Consecutive, self-control design over 8 weeks.

Trial run in Canada, unclear if single or 2 centre.

Participants

Total cohort: n = 11.

Age range: 9 - 24 years.

Gender split: no information.

Interventions

IMT: Inspiratory resistance, 15 minutes twice daily, no dosage.

Control: no details provided.

OutcomesIMS, Wmax, VO2max, VE and heart rate.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskDescribed as randomised, no details given.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
High risk

Performance bias: no details of the control training regimen are provided = high risk.

Dectection bias: observer blind = low risk.

Incomplete outcome data (attrition bias)
All outcomes
High risk

Two participants were unable to satisfactorily perform the outcome measure PIMax, due to expiration up to residual volume resulting in coughing. The authors do not stipulate whether this occurred during the intervention or control phase of the trial.

Intention-to-treat: unclear.

Selective reporting (reporting bias)Unclear riskInsufficient information available to arrive at a conclusion.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

Chatham 1997

Methods

Parallel design over 8 weeks.

Trial run in UK, not clear if single centre or 2 centres.

Participants

Total cohort: n = 18. Treatment group: n = 9; control group: n = 9.

All participants were adults, but no specific age details or information on gender split given.

Interventions

Intervention: computer-generated through range IMT (TIRE) at 80% of individual capacity.

Control: threshold loading device at 30% of peak; the measure used is not named.

OutcomesChronic Respiratory Disease Questionnaire ('mastery' and 'emotion' elements), RMS and RME.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskDescribed as randomised, no details given.
Allocation concealment (selection bias)Unclear riskInsufficient information available to arrive at a conclusion.
Blinding (performance bias and detection bias)
All outcomes
High risk

Perfomance bias: the training intensities employed (80% and "threshold" 30% training) could, potentially, have led the participants to know which group they were in.

Dectection bias: no reference to any blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk

Insufficient information available to arrive at a conclusion; no statistical data is presented for the control group.

Intention-to-treat: 3 from 18 (17%).

Selective reporting (reporting bias)Unclear riskAs this study (to date) is only published in abstract form it is unclear whether the reported outcomes are all that were analysed.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

de Jong 2001

Methods

Parallel design over 6 weeks.

Single centre trial in the Netherlands.

Participants

Total cohort: n = 16. Treatment group: n = 8; control group: n = 8.

Age range for total cohort 10 - 25 years. Treatment group: mean (SD) age = 17 (5.2) years; control group: mean (SD) age = 19 (5.5) years.

Gender split for total cohort: 8 male, 8 female. Treatment group: 4 male, 4 female; control: 4 male, 4 female.

Interventions

IMT: threshold loading: 20 minutes a day, 5 days per week, at 40% of PImax.

Control: threshold loading: 20 minutes a day, 5 days per week. at 10% of PImax.

OutcomesFEV1, FVC, Wmax, VO2max, VEmax, IME, perceived breathlessness, general fatigue, physical fatigue, reduced activity score, reduced motivation score, mental fatigue and dyspnoea.
NotesIME protocol: a commercially-available threshold-loading device (Threshold, Healthscan Products, Inc. USA) was used during an incremental loading procedure. In order to obtain pressures over 41 cm H2O an additional spring was inserted with a double-spring constant. Participants started inspiring from a threshold-loading device set at 30% of PImax for 2 min. The threshold load was then increased every 2 min in increments of 10% of Pimax. The maximal load was defined as the highest load which could be reached and maintained for at least 1 min as a percentage of PImax. The breathing pattern was not regulated.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskPatients were assigned to 1 of 2 groups by 5 patient factors: gender; age; FEV1; FVC; and BMI using the minimization method.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
High risk

Performance bias: both training intensities were low; however, no attempt was made to ascertain whether the participants knew if the received the training intensity.

Detection bias: no reference to any blinding.

Incomplete outcome data (attrition bias)
All outcomes
High risk

1 participant in the intervention group was withdrawn due to earache experienced whilst training at 40% of PImax.

Intention-to-treat: 1 from 15 (6%).

Selective reporting (reporting bias)Unclear riskInsufficient information available to arrive at a conclusion.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

Enright 2004

Methods

Parallel design over 8 weeks.

Single centre in UK.

Participants

Total cohort: n = 29. Treatment group 1: n = 9; treatment group 2: n = 10; control group: n = 10.

Age of total cohort (all adults): mean (SD) age = 22 (4.2) years. Treatment group 1: mean (SD) age = 24.8 (5.5) years; treatment group 2: mean (SD) age = 20 (4.7) years; control group: mean (SD) age = 21.3 (2.7) years.

Gender split of total cohort: 16 male, 14 female. Treatment group 1: 4 male, 6 female (according to table in paper); treatment group 2: 6 male, 4 female; control group: 6 male, 4 female.

All had similar age, height, weight and lung function at baseline.

Interventions

Intervention 1: IMT at 80% of "maximal inspiratory effort".
Intrevention 2: IMT at 20% of "maximal inspiratory effort".

Control: "No Training"

IMT is incremental maximal effort with progressively shorter rest periods, 3 times a week.

OutcomesFEV1(% predicted), FVC (% predicted), PImax, SPImax, heart rate, perceived exertion, dyspnoea and Chronic Respiratory Disease Questionnaire.
NotesSample size calculation undertaken such that study needed at least 9 patients in each group.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided.
Allocation concealment (selection bias)Unclear riskNo information provided.
Blinding (performance bias and detection bias)
All outcomes
High risk

Performance bias: the comparison was "no training" making it clear to the participants which arm they were in.

Dectection bias: outcome assessors at the final data collection session, although they did not state whether this was the case at the initial assessment or even if the same assessors carried out all the assessments.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk

No mention is made of whether all participants completed the trial or not. Nor are there any statistical indications.

Intention-to-treat: unclear.

Selective reporting (reporting bias)Unclear riskInsufficient information available to arrive at a conclusion.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

Heward 2000

Methods

Parallel design over 8 weeks.

Not clear if single or multicentre, authors from UK and USA.

Participants

Total cohort: n = 39 (19 with CF and 20 matched healthy controls). Treatment group CF: n = 9; control group CF: n = 10.

Age of CF adults: mean (SD) age = 22.5 (3.5) years; age of healthy adults: mean (SD) age = 21.5 (3.5) years.

Gender matched groups

Interventions

Treatment: IMT at 80% of "maximal effort", no dosage stated.

Control: no training.

OutcomesVC, TLC.
Notes

Only CF patients eligible in this review, 10 healthy adults in another IMT group and another control group.

Abstracts only available.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskDescribed as randomised, no details given.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
High risk

Performance bias: the comparison was "no training" making it clear to the participants which arm they were in.

Detection bias: no reference to any blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk

No information provided.

Intention-to-treat: unclear.

Selective reporting (reporting bias)High riskThe post-training pulmonary function results were not presented.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

Sawyer 1993

  1. a

    % predicted: the volume of air exhaled expressed as a percentage of the expected volume based on the physical attributes of the individual
    BMI: body mass index
    FEV1: volume of air exhaled over the first second of a forced exhalation
    FEV1/FVC = the ratio of FEV1 to FVC
    FRC: functional residual capacity
    FVC: total volume of air forcibly exhaled
    FEF25-75%: forced expiratory flow 25-75%
    IC: inspiratory capacity
    IME: inspiratory muscle endurance
    IMF: inspiratory muscle function
    IMS: inspiratory muscle strength
    IMT: inspiratory muscle training
    MEC: maximal exercise capacity
    MVV: maximum voluntary ventilation
    RME: respiratory muscle endurance
    RMS: respiratory muscle strength
    n: number of participants
    PImax: maximal inspiratory pressure
    RV: residual volume; i.e. the volume of air retained in the lungs following a maximal, voluntary exhalation (FVC)
    RV/TLC: the ratio of residual volume to total lung capacity
    SD: standard deviation
    SPImax: sustained maximal inspiratory pressure
    TLC: total lung capacity; i.e. the calculated maximum potential volume of an individual's lungs
    VC: the total volume of air that can be exhaled in any one breath
    VE(max): peak expired ventilation
    VO2max: peak oxygen consumption
    Wmax: maximum work load

Methods

Parallel design over 10 weeks.

Single centre trial in USA.

Participants

Total cohort: n = 20. Treatment group: n = 10; control group: n = 10.

Treatment group: mean (SD) age = 11.46 (2.45) years; control group: mean (SD) age = 9.76 (2.57) years.

No information on gender split.

Interventions

IMT: IMT at 60% PImax.

Control: Sham IMT at 10% PImax.

OutcomesFEV1, VC, FRC, IC, RV, TLC, RV/TLC, FEV1/FVC, MVV, exercise time.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskDescribed as randomised, no details given.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
High risk

Performance bias: there was a clear difference in the intensity of training although no attempt was made to ascertain whether the participants in the training groups knew if they received the training intensity.

Dectection bias: outcome assessors at the final data collection session, although they did not state whether this was the case at the initial assessment or even if the same assessors carried out all the assessments.

Incomplete outcome data (attrition bias)
All outcomes
High risk2 participants removed from analysis and the reasons for this were explained; however, it is unclear which group(s) they were in.
Intention-to-treat: unclear.
Selective reporting (reporting bias)Unclear riskInsufficient information available to arrive at a conclusion.
Other biasUnclear riskInsufficient information available to arrive at a conclusion.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    ACBT: active cycle of breathing technique
    IMT: inspiratory muscle training
    TIRE: test of incremental respiratory endurance

Howard 2000Inappropriate intervention - ACBT versus TIRE not IMT.
Irons 2012Inappropriate intervention - singing training and not IMT.
Keens 1977Study excluded as allocation not randomised.
Santana-Sosa 2013Although a form of IMT was used as an intervention it was used in combination with another exercise based intervention; therefore, it was impossible to attribute any observed changes to IMT alone.
Sartori 2008Observational study, no randomisation.
Vivodtzev 2013Inappropriate intervention - neuromuscular electrical stimulation prior to endurance training not IMT.

Ancillary