Respiratory Muscle Decline in Duchenne

Muscular Dystrophy

Mahmoud Halawa M.D

Benha University, Egypt

Duchenne Muscular Dystrophy(DMD)

The most common cause of muscular dystrophy in children

Prevalence: 1.3 to 1.8 per 10,000

X-linked recessive

Mutation of the dystrophin gene.

Muscle weaknessProgressive difficulty in walkingBreathing difficulties Heart diseaseLearning difficulties (the IQ can be below 75)Intellectual disability 

Symptoms usually appear between 2-3 y of age, the patient become wheelchair bound by age 12 and death occurs by age 20

Diagnosis:

Creatine phosphokinase (CPK)Electromyography (EMG)Electrocardiogram (EKG)Genetic analysisMuscle biopsy

Treatment:

No curative treatment till nowGene therapy still under trialCorticosteroidsACE inhibitorsMobility aidsBreathing assistanceSurgery

Hospital Armand Trousseau, Paris, France.

The study

Study Objective: analyze the trend of a number of respiratory parameters in patients with DMD to gain further information on the course of the disease.

Study Design: Retrospective analysis

Subject Selection: 28 boys with DMD, age range between 6-19 year old, who were followed between 2001 and 2011.

Methodology: Lung function, blood gases, respiratory mechanics, and muscle strength were measured during routine follow-up over a 10 years.

All patients were treated with ACE inhibitors

None received corticosteroids

Patients with vertebral arthrodesis surgery were not excluded

Only data before the initiation of NPPV were taken into account

Lung Function and Respiratory Muscle Tests

Non-Invasive

Non-Volitional Volitional

Invasive

Non-Volitional Volitional

•FRC•VT•VE•fR/VT

•FVC•SNIP•MIP•MEP•PEF•CPF

•Sniff Pes•Sniff Pdi•Pgas cough•TTdi•TTes

•Pdi• Pgas/ Pdi•PTPes•PTPdi•CL dyn

Statistical analysis

Mean + SDMedianRangeDecline in variables for each patient separatelyMean decline in each variable for all patients

Results

Discussion

This is the first study to report the natural evolution of a large number of respiratory parameters.

FVC may be more specific of disease progression from age of 10y

SNIP is very simple, feasible and reproducible to assess inspiratory muscle strength The decrease in SNIP% is very close to the decrease in MIP% SNIP values decline earlier compared to VC

Pgas cough was below normal in all the patients It is also feasible and reproducible to asses expiratory muscle strength

TTdi is useful to monitor the risk of developing diaphragmatic fatigue

The esophageal pressure time product/minute remained within normal values in the majority of patients

The diaphragmatic pressure time product/minute values were higher with a large intra- and inter-subject variability

Respiratory surveillance is an essential component of the care

Early involvement of the expiratory muscles

Sniff and cough are easier tests and interesting

PEF and CPF are simpler but less reliable

FVC and EFV1 are correlated to CPF

None of the non-volitional parameters was informative for the follow up of the disease Except VE

The conclusion: SNIP and FVC are the most informative parameters to follow the

disease progression in DMD

Pgas cough and TTdi are useful to monitor respiratory muscle decline and the risk of muscle fatigue

The monitoring of these parameters should be performed at an early age in order to follow the time course of the respiratory muscle decline

These parameters is helpful to guide therapeutic trials in young patients aiming at slowing disease progression

The main limitations:

Retrospective data collectionLow number of patientsDifficulties in follow up in some patients

Thank you