Pulmonary disease is the major cause of morbidity and mortality in spinal muscular atrophy types 1 and 2 and may occur in a small proportion of patients with spinal muscular atrophy type 3. Without respiratory support, infants who are unable to sit usually die before the age of 2 years. Pulmonary compromise is caused by a combination of inspiratory and expiratory muscle weakness, with greater involvement of expiratory and intercostal muscles. The diaphragm is relatively spared. In nonsitters, the result is a bell-shaped chest with sternal depression. In older sitters and walkers, respiratory function may be compromised further by scoliosis. Swallowing dysfunction and reflux are important contributors to pulmonary morbidity. Individuals tend to progress to daytime respiratory failure via a sequence of recurrent chest infections, nocturnal oxygen desaturation, nocturnal hypoventilation, and then daytime hypercarbia. In contrast to Duchenne muscular dystrophy, there is no strong correlation between pulmonary functional score and need for mechanical ventilation in spinal muscular atrophy. However, baseline assessment and longitudinal monitoring can identify those at risk for sleep-disordered breathing and ineffective clearance of secretions. There are several case series of the natural history of severe to mildly affected spinal muscular atrophy patients but no large prospective study of treatment intervention. The evidence base is limited by heterogeneous groups of patients with a mixture of neuromuscular disorders in natural history and intervention studies, variable classification of spinal muscular atrophy subtypes, and different respiratory support protocols employing a range of ventilators and cough assistance techniques. Case series and consensus conference evidence demonstrate that ventilatory support should be added at night if sleep-disordered breathing is present and cough assistance provided if cough efficiency is reduced. Figure 2 shows a flow chart for pulmonary natural history, assessment, and intervention in spinal muscular atrophy.

Respiratory Support

Written for FightSMA by Robert T. Leshner, M.D., Professor, Neurology and Pediatrics, Children's National Medical Center

Children with Spinal Muscular Atrophy Type I and Type II are especially vulnerable to respiratory complications. A regular program of respiratory therapy and breathing exercises may be very helpful for these youngsters. Precautions to avoid illness such as yearly influenza immunization should be given to most of these youngsters. The most emotionally charged issues in the management of children with SMA concern whether or not to initiate aggressive mechanical support when the breathing muscles begin to fail. Although the medical options are reasonably simple, the emotional turmoil of placing a child on a "breathing machine" is invariably painful for parents. Although many parents (and physicians alike) carry an image of a mechanical ventilator as a huge and unwieldy device, advances in technology have made ventilator use considerably easier and more convenient. Less invasive means of dealing with respiratory problems include many options. Parents should be trained in simple chest physiotherapy to help tide youngsters through their usual "coughs and colds." Because of difficulty with coughing, even a simple cold may result in saliva and mucous obstructing a child's airway. Techniques of postural drainage and chest percussion may prevent this complication.

Some children benefit from supplemental oxygen usually delivered through a small nasal tube. This is often helpful at night. Before initiating oxygen treatment, however, it must be determined that the brain is not using low concentrations of oxygen in the blood to determine how rapidly a child must breathe. Some of the normal regulation of breathing may be altered in children with chronic neuromuscular diseases. The decision to use supplemental oxygen should, therefore, be preceded by an evaluation by a pulmonary specialist.

Although the "standard" means of mechanical breathing support involves the surgical placement of a tube in the wind pipe (trachea), other less invasive means of breathing support are now being used. This includes devices termed "negative pressure" ventilators and external positive airway pressure support systems. The use of a BI-PAP has been especially helpful for many of our children with SMA. Instead of a tracheostomy, air is mechanically directed through the nostrils through a firmly, but gently fitted mask. This affords many of the benefits of a mechanical ventilator. It can only be emphasized that the decision to use any or all of these forms of respiratory support are emotionally charged and highly personal. Parents and children would be well advised to speak with other parents who have made this decision and to visit with children who have opted to utilize BI-PAP or tracheostomy based respiratory support.

Assessment and Monitoring

From Consensus Statement for Standard of Care in Spinal Muscular Atrophy

There is no formal study evaluating any protocol for routine pulmonary assessment of patients with spinal muscular atrophy. However, consensus was achieved within the pulmonary working group on current standard of care for spinal muscular atrophy. The following assessments should be used during baseline and subsequent evaluations of respiratory status and are listed by order of importance as identified by the Delphi survey. Assessment frequency depends on the clinical status and rate of progression of disease for each individual. Suggested frequency of evaluation is every 3 to 6 months, less often in stable walkers, and more frequently in clinically unstable nonsitters.

Nonsitters

Recommendations for respiratory assessment include evaluation of cough effectiveness, observation of breathing, and monitoring gas exchange. Respiratory muscle function tests are indirect measures of cough effectiveness and include peak cough flow, maximal inspiratory pressure, and maximal expiratory pressure. The majority of nonsitters with spinal muscular atrophy may be too weak or too young to perform pulmonary function testing. Therefore, the most useful evaluation of respiratory muscle function may be observation of cough ability. The physical examination also provides an important assessment of respiratory status including respiratory rate, work of breathing, presence of paradoxical breathing, chest wall shape, and skin color (cyanosis or pallor). Gas exchange monitoring, including pulse oximetry, can be used as a spot check during the day for hypoxemia and as a guide to direct airway clearance. For example, if oxygen saturation is less than 94%, airway clearance techniques should be used. Overnight pulse oximetry with chart recording can be used to screen for nocturnal hypoxemia. Routine overnight monitoring using pulse oximetry may help identify unsuspected hypoxic events but is usually very disruptive to the family due to frequent false alarms. Currently there are no data to support routine continuous oximetry monitoring. Further research is needed before recommending this as part of routine clinical care.

End-tidal carbon dioxide, transcutaneous CO₂, and serum bicarbonate measurement were also identified as important assessment tools. However, serum bicarbonate may give a false sense of reassurance, as normal values may exist despite significant respiratory compromise during sleep. End-tidal carbon dioxide and transcutaneous CO₂ are frequently difficult to obtain and not available routinely. If available, these measurements can be used to assess for sleep-related hypoventilation. The onset of hypoventilation is insidious, and patients may be clinically asymptomatic. Initially hypoventilation will occur in sleep (particularly rapid eye movement sleep), but as deterioration progresses, daytime respiratory function will be impacted. Polysomnography is a diagnostic tool during which respiration and sleep state are continuously monitored, and thus it identifies the presence and severity of sleep-disordered breathing. Polysomnography is useful in nonsitters, even in children without obvious symptoms, and can be used to initiate and titrate respiratory support. When polysomnography is not available, an alternative is to use a 4-channel sleep study that records end-tidal carbon dioxide or transcutaneous CO₂, oxygen saturation, heart rate, nasal airflow, and chest wall movement during sleep. In cases where neither polysomnography nor 4-channel study is available, overnight pulse oximetry with continuous CO₂ monitoring may provide useful information about nighttime gas exchange. However, this will not detect sleep-disordered breathing not associated with oxygen desaturation or CO₂ retention. Further study to better identify the optimal methods for evaluation and monitoring is recommended. Additional screening tests include a baseline chest x-ray to provide an initial reference point and for comparison during respiratory deterioration or unexplained hypoxemia due to unsuspected atelectasis. Although formal radiologic evaluation of swallowing was not ranked very highly for routine evaluation during this Delphi survey, the risk for dysphagia and aspiration is high in nonsitters. Therefore, formal evaluation of swallowing is indicated in cases of acute unexplained respiratory deterioration and recurring pneumonia. Arterial blood gases for routine monitoring of respiratory function are not recommended because the discomfort could result in apnea or spurious hyperventilation.

Sitters

Recommendations of respiratory assessment for sitters are similar to nonsitters and include physical examination and evaluation of cough effectiveness with respiratory muscle function tests (maximal inspiratory pressure, maximal expiratory pressure, and peak cough flow) as described above. In addition, sitters should be evaluated for presence and severity of scoliosis and consider further evaluation with radiographs. Additional recommended assessments include forced vital capacity and lung volume measurements during pulmonary function tests, assessment of sleep-disordered breathing, and pulse oximetry monitoring. Less important assessments identified for sitters include blood gas, CO₂ monitoring, and chest x-ray. Routine swallow study was not recommended for sitters unless clinically indicated.

Walkers

In general, spinal muscular atrophy walkers have relatively preserved pulmonary function until late into their disease course. Recommendations for routine assessment include complete pulmonary function tests, including spirometry, lung volumes, and respiratory muscle function tests. In addition, cough effectiveness and the physical examination are important routine assessments. Further evaluation should be directed by clinical symptoms and indications.

Anticipatory Respiratory Care

From Consensus Statement for Standard of Care in Spinal Muscular Atrophy

Providing families with information about options for care and anticipating future needs are crucial to respiratory management of spinal muscular atrophy. Nonsitters are the most fragile group, and early discussions should include the option of noninvasive ventilation and secretion management because of the rapid progression of the disease. Ongoing discussion of the family's desires for support should occur, and the result should be a negotiated care plan with maximums and minimums outlined.

In addition, anticipatory guidance and education for chronic care, illness management, and perioperative care should be provided. Day-to-day management should include understanding the child's baseline and deviations from his or her baseline, routine cough and secretion management techniques, understanding hypoventilation, and intervention. Illness management includes rapid access to specialty medical care providers, airway clearance and secretion management techniques, respiratory support (including noninvasive ventilation), nutrition and hydration management, and a low threshold to start antibiotics. Routine immunizations, including influenza vaccine, pneumococcus vaccine, and respiratory syncytial virus prophylaxis (palivizumab), are recommended.

Chronic Management

From Consensus Statement for Standard of Care in Spinal Muscular Atrophy

Essential to chronic management is discussion of the family's goals, which includes balancing caring for the child at home for as long as possible, long-term survival, quality of life and comfort, and the availability of resources. Goals of chronic management are to normalize gas exchange, improve sleep quality, facilitate home care, reduce hospitalizations and intensive care unit care, and reduce the burden of illness on the family. There is insufficient evidence, but based on experience and consensus, early aggressive and proactive intervention may prolong life without compromising quality of life.

Airway Clearance

Airway clearance is very important in both acute and chronic management of all patients with spinal muscular atrophy. Caregivers of these patients should learn to assist coughing in all patients with ineffective cough. These techniques include manually and mechanically assisted cough. Availability of mechanically assisted cough devices (mechanical insufflation-exsufflation) varies by country but is now widely accepted in management of neuromuscular disease in the United States. Daily assisted cough is recommended in more severely affected patients. Secretion mobilization techniques are also helpful and include chest physiotherapy and postural drainage. Oximetry should be used to provide feedback to guide therapy. Oral suctioning can assist in secretion management after assisted coughing. There is no evidence to support specific secretion mobilization devices such as high frequency chest wall oscillation and intrapulmonary percussive ventilation in the spinal muscular atrophy population for chronic management.

Respiratory Support

In patients with daytime hypercapnia, respiratory support is clearly indicated. In children with sleep-disordered breathing, nocturnal noninvasive ventilation reduces symptoms of sleep disturbance, nocturnal sweating, and morning headaches and improves appetite and concentration. Objectively, noninvasive ventilation reduces respiratory disturbance index, improves sleep stage distribution, and enhances quality of life. In a randomized controlled trial using mixed groups of patients with neuromuscular disease who showed nocturnal hypoventilation and daytime normocapnia, noninvasive ventilation significantly improved nocturnal blood gas tensions. Noninvasive ventilation with bilevel positive pressure support has been studied most frequently, although there is no evidence to suggest any 1 type of ventilator interface is superior. In addition, the optimal settings for noninvasive ventilation have not been established. In general, noninvasive ventilation settings are individualized to achieve adequate inspiratory chest wall expansion and air entry and normalization of oxygen saturation and end-tidal carbon dioxide or transcutaneous CO₂ measurements. Noninvasive ventilation should be combined with airway clearance techniques.

In nonsitters, care without ventilation support is an option if the burden of treatment outweighs benefit. Noninvasive ventilation can be used palliatively to facilitate discharge to home from a hospital and reduce work of breathing. Continuous positive airway pressure may be an option in a very young nonsitter infant who is not synchronous with bilevel positive airway pressure and can be used with the goal of transitioning to bilevel positive airway pressure. Use of noninvasive ventilation with high-span bilevel positive airway pressure, even for short daytime periods, may improve chest wall and lung development and reduce ribcage and sternal deformity in nonsitters and sitters, resulting in potential beneficial effects on pulmonary function. Uncommonly, adult walkers may develop sleepdisordered breathing or acute ventilatory failure at the time of a chest infection or intercurrent event (eg, surgery). Noninvasive ventilation is an appropriate intervention and may be required during sleep chronically.

Tracheotomy for chronic ventilation is a decision that needs to be carefully discussed if requested by parents. In nonsitters, this is controversial and an ethical dilemma. There is a large spectrum of options that can be provided, ranging from no respiratory support to noninvasive ventilation to tracheotomy and mechanical ventilation. Our recommendation is to explore options with the family regarding the child's potential, quality-of-life issues, and family's desires. Palliative care is an option for nonsitters. It should be noted that noninvasive ventilation can be used as a routine therapy or as a palliative tool. A key goal is to prevent pediatric intensive care unit stays and avoid tracheotomy if possible. If supportive ventilation is chosen by the family, noninvasive ventilation is recommended.

Additional Management

Recommended additional therapies are routine vaccinations, appropriate nutritional support orally or via a feeding tube, hydration management, and medical or surgical gastroesophageal reflux disease management. In addition, medical management for saliva control may be considered. Inhaled bronchodilators should be considered in children with asthma or bronchial hyperresponsiveness. Use of these agents in other situations requires further evaluation. There is no evidence to support the use of mucolytics on a chronic basis.

Perioperative Care

From Consensus Statement for Standard of Care in Spinal Muscular Atrophy

Patients with spinal muscular atrophy are at high risk for postanesthesia complications, which may lead to prolonged intubation, nosocomial infections, tracheotomy, and death. Perioperative complications include upper airway obstruction, hypoventilation, and atelectasis from impaired cough and impaired mucociliary clearance due to anesthetic agents. Postoperative pain may exacerbate respiratory compromise. Noninvasive ventilation associated with aggressive airway clearance techniques can successfully treat hypoventilation and airway secretion retention.

It is crucial that the patient's respiratory status be optimized before surgery. Preoperative evaluation, including pulmonary consultation, is strongly recommended. The assessment of respiratory function should include a physical examination, measurements of respiratory function and cough effectiveness, chest x-ray, and, if at risk, an evaluation for sleep-disordered breathing. In addition, complicating factors should be considered, including oropharyngeal aspiration, gastroesophageal reflux, and asthma. If measurements of respiratory function and/or sleep study are abnormal, nocturnal noninvasive ventilation and assisted coughing techniques may be indicated before surgery. The patient should become familiar with these techniques prior to surgery. The anesthesiology preoperative evaluation should include assessment for possible difficult intubation due to jaw ankylosis. If present, intubation should be performed by fiberoptic bronchoscopy.

Postoperative management should be determined by preoperative respiratory function and the type of surgery performed. Patients with normal cough clearance and relatively preserved muscle function are not at an increased risk for postoperative complications. Patients with decreased respiratory muscle strength require close monitoring and aggressive respiratory management. Any patient who requires respiratory support during sleep will require similar respiratory support in the immediate postoperative course. Extubation in the recovery room to noninvasive ventilation should be planned as a bridge to weaning to the patient's baseline respiratory support. Careful planning and coordination with the hospital respiratory therapists are crucial for success in this setting. Patients with continuous ventilator support requirements (either via noninvasive interface or via tracheotomy tube) or patients who receive muscular blocking agents during surgery are best transferred directly from the operating room to the intensive care unit. Patients are encouraged to bring their personal devices, such as noninvasive ventilation and mechanical insufflation-exsufflation-E machines, to use in the postoperative period because the availability of these devices in hospitals may be limited. Although oxygen is used frequently in the postoperative setting, it must be applied with caution in the patient with spinal muscular atrophy. Hypoxemia secondary to hypoventilation may be mistaken with hypoxemia due to other causes, such as mucus plugging and atelectasis. End-tidal carbon dioxide or transcutaneous CO₂ monitoring or arterial blood gas analysis will facilitate appropriate oxygen use. Adequate pain control will aid in preventing hypoventilation secondary to splinting. Postoperative pain management should be titrated to promote airway clearance and minimize respiratory suppression. Transient increased respiratory support may be needed while controlling postoperative pain.

Acute Care Management

From Consensus Statement for Standard of Care in Spinal Muscular Atrophy

The goal of acute management is to normalize gas exchange by reducing atelectasis and enhancing airway clearance where possible by noninvasive respiratory support. Blood gas monitoring may be of benefit.

Airway Clearance

For nonsitters, sitters, and walkers experiencing acute illness, airway clearance with manual cough assist or mechanical insufflation-exsufflation, together with oral or airway suctioning, chest physiotherapy, oximetry feedback to guide airway clearance, and postural drainage, are important and recommended. Assisted cough techniques are preferred over deep suctioning and bronchoscopy.

Respiratory Support

Nonsitters. In acute illness, a vicious cycle of added ventilatory load, increased respiratory muscle weakness, and ineffective secretion clearance leads to ventilatory decompensation. Acute use of noninvasive ventilation reverses these features. Continuous positive airway pressure is not indicated in this situation because it does not reduce the ventilatory load. In nonsitters and sitters already using nocturnal noninvasive ventilation, daytime use may be required during acute illness, and airway clearance techniques can be carried out during noninvasive ventilation. Noninvasive ventilation in combination with airway clearance techniques may reduce the need for intubation. Oxygen therapy entrained into the noninvasive ventilation circuit should be used to correct oxygen desaturation, after inspiratory and expiratory positive pressure settings are optimized and airway clearance techniques are optimally utilized. If a noninvasive approach fails, nonsitters can be intubated and mechanically ventilated as a short-term measure. After recovery from the acute illness and arterial oxygen saturation on room air has normalized, they should be extubated back to noninvasive ventilation. Decision making about escalation to intubation should be carried out in advance as part of anticipatory care planning. In nonsitters with increasingly frequent acute pulmonary infections, tracheotomy and ventilation can be considered but may not improve quality of life or reduce hospitalizations. A tracheotomy is not an acute intervention. A noninvasive approach is preferred where feasible. In some nonsitters, with deteriorating function, it may be appropriate to redirect care to a palliative approach.

Sitters. For those already using nocturnal noninvasive ventilation, daytime noninvasive ventilation may be needed during acute illness. Noninvasive ventilation in combination with airway clearance techniques may reduce the need for intubation. Oxygen therapy and need for transient intubation should be carried out as outlined above for nonsitters. Continuous positive airway pressure and/or a tracheotomy are not appropriate interventions in sitters.

Walkers. Walkers may need noninvasive ventilation during an acute illness. Noninvasive ventilation in combination with airway clearance techniques may reduce the need for intubation. Oxygen therapy and need for transient intubation should be carried out as outlined above for nonsitters. If noninvasive ventilation was needed during an acute illness, noninvasive ventilation should be considered for home use. Continuous positive airway pressure and/or a tracheotomy are not appropriate interventions in walkers.

Additional Management

For nonsitters, sitters, and walkers, recommended additional therapies are antibiotics, adequate nutritional support via nasogastric or nasojejunal or gastrostomy tube, hydration, and gastroesophageal reflux management (see more details in the next section). In patients with bronchial hyperresponsiveness or asthma, bronchodilator therapy and inhaled steroids may be indicated. Uses of inhaled mucolytics, bronchodilators, and corticosteroids are areas in need of further research.

Conclusion

From Consensus Statement for Standard of Care in Spinal Muscular Atrophy

Pulmonary disease is the major cause of morbidity and mortality in spinal muscular atrophy types 1 and 2. Respiratory muscle weakness results in impaired cough and ability to clear lower airway secretions, lung and chest wall underdevelopment, and hypoventilation. Respiratory care of patients with spinal muscular atrophy is essential to their survival and quality of life. The pulmonary working group has achieved the following consensus recommendations:

Referral for respiratory care evaluation and discussion of options should occur shortly after diagnosis. Key components of the respiratory assessment include evaluation of cough effectiveness, observation of breathing, and monitoring gas exchange.
Chronic respiratory management includes providing methods for airway clearance, including mechanical insufflation-exsufflation or manual cough assist and noninvasive ventilatory support. Routine immunizations are also recommended.
Discussion with families about the options for respiratory care and identifying the goals for chronic and acute respiratory care should occur early in the disease course and continue in an ongoing dialogue.
Acute respiratory illness management requires increased airway clearance and secretion management techniques using mechanical insufflation-exsufflation or manual cough assist, increased respiratory support (including noninvasive ventilation), nutrition and hydration management, and a low threshold to start antibiotics.
Perioperative care includes a thorough preoperative evaluation of respiratory status, ideally by a pulmonologist, and anticipatory guidance of the surgical team and postoperative management team regarding optimal care.

Spinal Muscular Atrophy Pulmonary Care

Overview of Pulmonary Problems in Spinal Muscular Atrophy

Respiratory Support

Assessment and Monitoring

Nonsitters

Sitters

Walkers

Anticipatory Respiratory Care

Chronic Management

Airway Clearance

Respiratory Support

Additional Management

Perioperative Care

Acute Care Management

Airway Clearance

Respiratory Support

Additional Management

Conclusion

Pulmonology and Respiratory Specialists

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