DISCUSSION
Failure of ventilatory mechanics is a major cause of mortality in DMD. A
study conducted by McDonald and colleagues (2016) with 114
children, detected important pulmonary complications in 34% of them. It
is estimated that 55–90% of DMD’s patients die from respiratory
insufficiency between 16.2 and 19 years of age10. The spectrum of symptoms triggered by the
involvement of the pulmonary musculature ranges from frequent
obstructions, due to the weakening of upper airway muscles, to a chronic
restrictive breathing pattern, as a result of chest-wall muscles
degeneration. If spinal muscles are affected, orthopedic abnormalities
may be present, such as scoliosis. These alterations, when associated
with difficulty in expectorating and coughing, can lead to chronic
aspirations, atelectasis, and fibrosis 11,12.
One of the main life-threatening conditions related to DMD is
sleep-disordered breathing, especially nocturnal hypoventilation, an
independent predictor of severity, and a marker of ventilatory failure
onset. It is more prevalent in the Rapid Eye Movement stage of sleep and
can be identified by Polysomnography (PSG) with transcutaneous CO2
capnography 3. In a 5-year retrospective
analysis performed with 34 male patients with DMD, Hoque et al
(2016) observed that 15 of them didn’t present any abnormalities in
PSG, 10 had obstructive sleep apnea, and 7 developed hypoventilation13. Beyond PSG studies, it is important to
continuously monitor the pulmonary function of DMD patients, assessing
forced vital capacity, ventilatory muscle strength, and oximetry, in
order to recognize signs of clinical worsening like daytime
hypoventilation 12.
During the ambulatory stage, frequent spirometries should be performed
since the child is 5 years old. Interestingly, the Forced Vital Capacity
curve increases for a certain period, following the patient’s growth,
until it reaches a plateau and begins to decline. It is important to
note that the beginning of lung function deterioration is not always
accompanied by symptoms, for this reason, serial evaluations are
essential 6. A reduction in the values of FVC
and PEF can be detected even before the first motor manifestations.
According to Mayer et al (2018) , these parameters suffer an
annual drop of 5%, from 5 to 24 years of age3. Advanced stages of Duchenne usually
require hospital management. During this period, surgical correction for
orthopedic abnormalities may be necessary. In the face of significant
reductions in chest wall compliance, especially if FVC declines by more
than 40%, the use of non-invasive ventilation (NIV), such as a manual
self-inflating bag, is indicated, because of its capacity to contain the
loss of FVC to only 0.5% per year 6, 14. In
spite of this correlation, there is no high-level evidence to precisely
associate the levels of FVC and PEF with the need for airway cleaning
devices or mechanical ventilation 3.Nocturnal ventilation is necessary when PSG studies identify a SpO2 of
88% or less, an increase in petCO2 of 10 mmHg above the daytime
baseline or petCO2 levels greater than 50 mmHg for more than 2% of
sleep time 6.
Manually assisted coughing may also be required. It is recommended for
patients to have oximeters in their homes and increase the frequency of
insufflations whenever O2 saturation is less than 95%, in order to
reduce the recurrence of pneumonia 6, 15. For
the same reason, authors support the use of antibiotics in the presence
of early pulmonary infection signs, like fever, hypoxemia, leukocytosis,
high C-reactive protein levels, expectoration, or infiltrations on chest
X-ray 16. Brazilian consensus on
Duchenne muscular dystrophy (2018) also emphasizes the need for an
immunization regimen that includes 3 doses of Pneumococcal Conjugate
Vaccine (Pn10 or Pn13), 1 dose of Pneumococcal Polysaccharide Vaccine
(Pn23) and annual doses of Anti-Influenza Vaccine in children with DMD,
particularly those using corticosteroids 17.
Steroids, like Prednisone 0.75mg/Kg and Prednisolone 0.75mg/Kg, are
first-line drugs used in DMD’s therapy, as a second alternative,
Deflazacort 0.9–1 mg/Kg can be prescribed. Meta-analyses showed its
potential to increase the life expectancy of the patients by promoting
sarcolemmal stabilization, improving motor function, preventing spine
deformities, giving longer independent waking, and, mainly slowing down
the progression of lung and cardiac injury2,18. Glucocorticoids regimen should be
started in boys after 2 years of age who begin to present motor deficits
or over 5 years old, regardless of their degree of
functionality. Frequently monitoring the possible adverse
effects of the medication is crucial, as these patients often use
continued corticosteroids throughout life. It is generally recommended
that the interval between evaluations does not exceed 6 months, paying
attention to cushingoid features and ophthalmological manifestations.
Intolerable side effects are one of the few reasons for discontinuing
these drugs in DMD 2.
Antioxidants, like Idebenone, despite not being approved by the Food and
Drug Administration, have also proved valuable in maintaining the DMD
pulmonary function 2. A research conducted byMcDonald et al (2016) demonstrated a noticeable increase for
FVC% and a reduction in the incidence of bronchopulmonary adverse
events in favor of Idebenone when compared to placebo10. Other promising therapies described in
the literature are read-through agents (Ataluren), exon skipping agents
or even micro-dystrophin gene therapy, such as Drisapersen and
Eteplirsen, which, through the deletion of defective exons, allow the
production of functional dystrophin or even stem cell transplant, but
like Idebenone, require further studies to be consolidated as a
treatment for DMD 2,19.