To estimate the effects of inspiratory muscle training on pulmonary function test parameters among children and adolescents with chronic neuromuscular diseases.

To estimate the effects of inspiratory muscle training on requirement for assisted ventilation, respiratory infections, quality of life, pulmonary function test parameters, and overnight oximetry parameters, among children and adolescents with chronic neuromuscular diseases.

To determine the adverse events of inspiratory muscle training among children and adolescents with chronic neuromuscular diseases.

1. Cochrane Central Register of Controlled Trials (CENTRAL)

2. PubMed

3. MEDLINE (Ovid)

4. EMBASE (Ovid)

5. Ongoing clinical trials were identified at http://www.clinicaltrials.gov/ and http://apps.who.int/trialsearch/

We will include randomized controlled trials or quasi randomized controlled trials that have evaluated any one of the following comparisons:

i. Inspiratory muscle training in addition to standard care versus standard care alone.

ii. Inspiratory muscle training versus sham therapy.

iii. One modality of inspiratory muscle training versus another.

Chronic neuromuscular diseases in children and adolescents that cause respiratory muscle weakness are the conditions of interest in this systematic review. Both inherited and acquired neuromuscular diseases will be considered for inclusion. We will exclude studies that have enrolled patients with quadriplegia and respiratory muscle weakness due to spinal cord injury or transverse myelitis. Studies that have enrolled patients diagnosed with polyneuropathies secondary to nutritional deficiencies like vitamin B12 deficiency will be excluded.

The studies that had enrolled children and adolescents less than 20 years of age who are diagnosed with any chronic neuromuscular disease by any valid diagnostic method/criteria will be included in this review. Criteria for diagnosis will depend upon the individual neuromuscular disease. The diagnostic criteria include clinical features, electrophysiological characteristics, muscle biopsy and/or genetic tests. We plan to include studies that enrolled patients who were on assisted ventilation at the time of enrollment in the trial.

Intervention - we will include trials that have evaluated any one of the modalities of inspiratory muscle training such as threshold loading, resistive loading and normocapnic hyperpnoea. The intervention should have been employed at least five times a week for at least three weeks duration to be included in this review.

Comparator - studies that have compared inspiratory muscle training against sham therapy or no inspiratory muscle training are eligible for inclusion in this review.

Chronic neuromuscular diseases that are known to cause respiratory muscle weakness are the disease of interest for this systematic review.

Primary outcomes

Pulmonary function test parameters that will be considered for primary outcome measures are:

i. Maximum Inspiratory Pressure (PImax).

ii. Inspiratory muscle endurance (IME).

iii. Maximum voluntary ventilation (MVV) (absolute and % predicted for gender and height).

iv. Forced vital capacity (absolute and % predicted for gender and height).

For ease of combining data from different studies and for comparability, the time points for assessment of these outcomes will be categorized as:

early (between 1-3 months after the commencement of intervention),

medium term (3-6 months after the commencement of intervention), and

long term (between 6-12 months after the commencement of intervention).

Secondary outcomes

1. Proportion of patients requiring assisted ventilation assessed at medium term and long term.

2. Number of lower respiratory tract infections (confirmed by chest X ray film or those requiring antimicrobial treatment with or without hospitalizations) assessed at early, medium and long term.

3. Quality of life (as assessed by any valid scale) assessed at early, medium and long term.

4. Cough peak flow (L/min, %predicted for gender and height) assessed at early, medium and long term.

5. Overnight oximetry parameters assessed at early, medium and long term.

i. Mean nocturnal oxygen saturation

ii. Percentage of recording time with SpO2 < 90%

6. Incidence and nature of ‘serious’ and ‘non serious’ adverse events reported.

Serious adverse events: An adverse event is any undesirable experience associated with the medical intervention in a patient. The event is serious if it includes death, any life-threatening event, hospitalization (initial or prolonged), disability (or permanent damage) or any intervention required to prevent permanent impairment or damage (FDA definition adapted from http://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm)

Non serious adverse events: adverse events that are not covered under serious adverse events such as ear ache, minor injuries and respiratory muscle pain.

For ease of combining data from different studies and for comparability, the time points for assessment of these outcomes will be categorized as:

early (between 1-3 months after the commencement of intervention),

medium term (3-6 months after the commencement of intervention), and

long term (between 6-12 months after the commencement of intervention).

One review author (LK) will screen the electronic and manual search results to find clinical trials that are relevant to the research question and will obtain the full text of all relevant studies. Two review authors (LK, SG) will independently apply the inclusion and exclusion criteria. Disagreements, if any, will be resolved by discussion and adjudication with third author (SK). We will contact the authors of the original trials for clarifications, if needed. We will scrutinize all the trials according to the year of publication, study site(s), and interventions to ensure that multiple publications from the same trial are included only once in the review. We will record the reason(s) for exclusion systematically.

Data extraction and management - two review authors (LK, SG) will independently extract the data by using a pre-designed data extraction form. Disagreements, if any, will be resolved by discussion with the third author (RL). We will seek additional information from the authors of original trials whenever needed. One review author (LK) will enter the data in Review Manager 5. Another review author (RL) will independently cross check the entries for any errors.

We will extract the following data:

1. Study characteristics: study ID, trial authors, year of publication, citation, study site.

2. Patient characteristics: method of confirmation of the diagnosis, mean age and age range, inclusion and exclusion criteria, duration between disease onset and inclusion in the trial, disease severity and co morbidities.

3. Methodology: randomization sequence generation, allocation concealment, blinding, study measurements.

4. Intervention and comparator arms: details of intervention in each arm including intervention name, intensity, frequency, duration.

5. Total number of patients enrolled and number of patients assigned to each intervention arm, total number of patients analyzed and lost to follow up in each arm.

6. Concomitant medication(s) and other co interventions.

7. Study outcomes including number of patients who achieved each outcome of interest in each intervention arm.

Two review authors (LK, RL) will independently assess the risk of bias using The Cochrane Collaboration’s Risk of bias tool. The risk of bias assessment will not be blinded to the authors or the study site(s).

The items included for risk of bias assessment will be:

1. Sequence generation,

2. Allocation sequence concealment,

3. Blinding,

4. Incomplete outcome data,

5. Selective outcome reporting, and

6. Other potential sources of bias (i.e. was there any other bias that will qualify the study for high or unclear risk of bias?).

Quantitative data will be entered into Reviw Manager version 5 and analyzed using Cochrane MetaView. When two or more trials present their data derived from the same instrument of evaluation with the same units of measurement, we will pool their results in meta-analyses. We will use adjusted summary statistics if feasible; otherwise unadjusted results will be used. For any dichotomous outcomes, we will calculate risk ratios for each study and we will pool them in meta-analyses. For continuous outcomes, we will pool the mean differences between the intervention arms if all trials measured the outcome on the same scale. Otherwise we will calculate standardized mean differences and will pool them, as discussed above. Random effects or fixed effect models will be used depending on the presence or absence of heterogeneity across the studies. If possible, studies making different comparisons will be synthesized using the methods described by Bucher et al. We will assess the quality of the evidence using the GRADE approach.

We will conduct sub group analysis in following subgroups to explore heterogeneity:

1. Patients who are ambulatory vs patients who are non-ambulatory.

2. Patients who are on assisted ventilation and patients who are not on assisted ventilation.

3. Different modalities of inspiratory muscle training (threshold loading, resistive loading and normocapnic hyperpnoea).

4. Intensity of intervention (high intensity (> 60% of PImax) versus low intensity (<60% of PImax)).

Lakshminarayanan Kannan

Senior Resident,

Department of Pediatrics

Room #3058

Teaching block

All India Institute of Medical Sciences

Ansari Nagar

New Delhi, 110029

India

dr_kln@yahoo.co.in

All India Institute of Medical Sciences, New Delhi

www.aiims.edu

Dr LAKSHMINARAYANAN KANNAN, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi
Dr Sheffali Gulati, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi
Dr Rakesh Lodha, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi
Professor Sushil K Kabra, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi
Professor Kameashwar Prasad, Department of Neurology, All India Institute of Medical Sciences, New Delhi
Professor Vinod K Paul, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi

02 January 2012

15 September 2012

None

None known

English

India

Subject indexing assigned by CRD

Adolescent; Breathing Exercises; Child; Chronic Disease; Humans; Neuromuscular Diseases; Respiratory Insufficiency; Respiratory Muscles

07 September 2012

07 September 2012