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.