Introduction 

Orthopnea, shortness of breath when lying down yet relieved when standing or sitting up, is one of the significant challenges in the neuromuscular disorders (NMDs). Due to NMDs’ effect on nerves that control voluntary muscles, the potential of impacting respiratory function can exacerbate difficulty breathing in certain positions. As a result, orthopnea can significantly increase discomfort, disrupt sleeping patterns, diminish quality of life and overall well-being. Understanding the mechanisms behind orthopnea in the context of NMDs is crucial for developing targeted management and interventions to improve the holistic well-being of those affected. This introduction will set the stage for exploring the intricate relationship between orthopnea and neuromuscular disease. 

Neuromuscular disorders and respiratory function

Neuromuscular disorders (NMDs) are conditions that affect voluntary muscle control, thus various bodily functions, including breathing. With disruptions to the central respiratory drive, cervical spine (C3-5) and/or phrenic nerve, respiratory muscles (e.g., diaphragm and intercostal muscles) could potentially become weakened, paralyzed, or uncoordinated and cause various respiratory impairments.¹ 

Some NMDs with respiratory involvement include:

• Guillain-barré syndrome
• Amyotrophic lateral sclerosis (ALS)
• Muscular dystrophies (MD)
• Spinal muscular atrophy (SMA)
• Myasthenia gravis (MG)
• Post-polio syndrome
• Mitochondrial myopathy 

Respiratory muscle weakness 

Respiratory muscle weakness (RMW), which impacts the proper function of the diaphragm, intercostal muscles, and other breathing muscles, has been common among NMDs. 

Diaphragm (primary breathing muscle) weakness typically results in a reduced lung volume and inefficient gas exchange,  resulting in the ability and effectiveness of inhalation and exhalation. Weakness in intercostal muscles interferes with chest expansion for sufficient airflow during inhalation, which makes breathing increasingly challenging over time.² 

What is orthopnea?

Orthopnea is shortness of breath when lying on your back, typically relieved by standing or sitting upright. While it is almost a sign of an underlying medical condition, it may occur randomly or worsen over time, depending on the various underlying conditions. Most of these are related to NMDs, such as congestive heart failure, pulmonary hypertension (PH), edema, COPD, pneumonia, and diaphragm paralysis.   

This typically occurs when lying in the supine position (face upwards), as gravity either redistributes body fluid or pressurizes the diaphragm. This makes it harder for the weakened heart, lung or diaphragm to cope with increased pressure in the chest and induces difficulty breathing.³

Mechanisms of orthopnea in NMDs 

Orthopnea results from several interrelated mechanisms affecting various respiratory, bulbar muscles, and the cardiovascular system.^4,5

Diaphragmatic weakness

The diaphragm is the primary respiratory muscle that takes up 80% of inhalation work and can become weakened or progressively weaker due to NMDs.⁶ As abdominal organs shift upward when lying down, the weakened diaphragm becomes even more pressurized. This diminishes diaphragmatic contractility and movements, reducing total lung capacity (TLC) and vital capacity (VC)^.7,8 Thereby limiting breathing ability and efficiency, resulting in orthopnea.  

Impaired chest wall mechanics

Orthopnea in NMDs can be attributed to chest wall mechanical impairments due to intercostal muscle weakness. When elastic muscles surrounding the thoracic cavity are weakened, the ribcage is less able to expand outward, restricting lung inflation and airflow.1 As gravity pulls the chest wall and abdominal organs towards the diaphragm when lying down, this pressurizes the weakened respiratory muscles in overcoming such mechanical disadvantages. Orthopnea and the emergence of paradoxical breathing are results of compensation.^2,8   

Loss of accessory muscle function

Accessory (shoulder girdle) muscles assist inhalation during stress or exertion.⁹ In NMDs such as various muscular dystrophies (MDs) primarily affecting (proximal) accessory muscles,  their weakness or loss comprises the compensation towards weakened diaphragmatic and intercostal muscles. Despite accessory muscle involvement when inhaling upright, the supine position that limits their use would have challenged the airflow and oxygen demands, thereby triggering orthopnea among individuals with MDs.^10,11

Reduced lung volumes and atelectasis

Reduced lung volume during the supine position could cause orthopnea in NMDs. Respiratory muscle weakness among NMDs could impair lung inflation, resulting in focal atelectasis (collapse of lung alveoli).⁸ This could further reduce oxygenation while intensifying the sense of breathlessness when lying flat, due to the fully lung expansion inability and increased breathwork load. Furthermore, ineffective coughing and airway clearance difficulties could further increase the risk of respiratory complications.¹² 

Cardiovascular interactions

While orthopnea in NMDs primarily results from respiratory muscle weakness, it could further be intensified by cardiovascular problems. Supine position increases venous blood return to the heart, elevating pulmonary pressures that further stress the weakened respiratory muscles. This is particularly distressing among those at risk of hypoxia and hypercapnia respiratory failure in advanced NMDs.^3,13,14  

Signs and symptoms 

As a first indicator of RMW among NMDs, despite the general increasingly noticeable shortness of breath, orthopnea  often presents as follows:^2,4,5

Dyspnea when supine

When respiratory symptoms begin, difficulty breathing is often first noticed when lying down. Individuals will need to sleep with several pillows or in a recliner chair, as an elevated position makes breathing easier.  

Morning headaches 

Shallow breathing and hypoventilation during sleep could lead to CO₂ retention, resulting in morning headaches and lethargy. 

Increased daytime fatigue

With nocturnal hypoventilation (impaired breathing during sleep), hence poor sleep quality, individuals often awake feeling unrefreshed, experiencing excessive daytime sleepiness and depleted cognitive functioning. 

Decreased breath sounds

During physical examination or sleep, reduced breath sounds or a shallow breathing pattern may also be present.  

Paradoxical breathing 

Paradoxical (abdomen inward movement) breathing can also be observed to compensate for the significant diaphragmatic and chest muscle weakness. 

Diagnosis and assessment 

Orthopnea among NMDs is often diagnosed and assessed through a comprehensive combination of clinical evaluation, medical history review, and diagnostic tests.^3,4

Clinical evaluation

A detailed medical history review focusing on symptom onset, frequency, and severity of orthopnea is conducted in which physicians ask about sleep patterns, fatigue levels and use of pillows at night. A physical examination is done to assess respiratory effort, lung auscultation, and observe if a paradoxical breathing pattern is present. 

Patient-reported outcomes 

Standardized questionnaires, such as the Modified Medical Research Council (mMRC) Dyspnea Scale, may also be used to quantify the severity of dyspnea (shortness of breath), to provide valuable insights into the impact on daily functioning and quality of life. 

Diagnostic tests

Several objective assessments are done to  confirm orthopnea among NMDs, whilst evaluating respiratory function:

Chest X-ray

Chest X-ray, as a first-line diagnostic tool for dyspnea, is usually used to rule out conditions such as heart failure, COPD, pneumonia, lung cancer, tuberculosis (TB), or ribcage injuries.    

Pulmonary function testing (PFTs): spirometry 

Pulmonary function testing (PFTs), particularly spirometry, is used in assessing the lung volumes, capacities, air flow rates, and respiratory muscle involvement among NMDs. Orthopnea is typically indicated by a reduced forced vital capacity (FVC) when comparing sitting and lying positions. 

Arterial blood gas (ABG) analysis 

Arterial blood gas (ABG) analysis checks gas exchange and acid-base status in blood, to identify potential hypoxemia or hypercapnia, which indicates respiratory muscle weakness, while supporting the diagnosis of orthopnea among NMDs.  

Sleep studies 

Polysomnography can be utilized to assess breathing patterns, oxygen saturation, and ventilation during sleep, to identify nocturnal hypoventilation and respiratory disturbances associated with orthopnea among the NMDs population. 

Despite the aforementioned, the diagnosis and assessment of orthopnea will need to be very cautious of the overlapping respiratory symptoms, variabilities in presentations, potential comorbid, difficulties in accurate patient self-report, as well as its dynamicity and lack of standard diagnostic criteria. 

Treatment and management

A multidisciplinary approach is used to treat and manage orthopnea among the NMDs population by addressing the underlying respiratory muscle weakness. 

Physical (respiratory) therapy

There are physical therapies targeting respiratory muscle training for overall functioning and endurance. Specialized respiratory therapeutic techniques such as breathing exercises, chest physiotherapy, assisted coughing and airway clearance methods to improve lung function and secretion clearance, aid in preventing respiratory complications underlying RMW.  

Postural modifications

Individuals with NMDs who experience orthopnea are usually advised to sleep with their head and shoulder elevated, with specialized pillows or an adjustable bed to ease orthopnea by reducing the pressure on weakened respiratory muscles.³ 

Assistive devices

Respiratory assistive devices, non-invasive ventilation (NIV) such as CPAP or BiPAP machines are used to deliver air pressure to facilitate breathing during bedtime.  It opens up the upper airway to relieve obstructive sleep apnea, and positive air pressure is used to ensure a bigger, normal-sized breath. Also, it ensures a certain breathing rate for those with central sleep apnea. Cough-assist devices are used to stimulate a deep cough to prevent respiratory infections and ensure respiratory health.⁴ 

Furthermore, having appropriate medical interventions with regular monitoring that target the underlying NMDs helps optimize functioning and disease progression. 

Progression, prognosis and complications  

Though orthopnea often evolves slowly among NMDs, progression and prognosis are still varied and mostly are dependent on the diverse neuromuscular pathologies and the subsequent management. Some include:

• Later in muscular dystrophies, along with progressive muscle weakness
• Highly varying disease courses, associated with bulbar weakness in ALS
• Sudden respiratory failure during the myasthenic crisis in MG
• Highly variable, exacerbated by physical exertion or illness, along with exercise intolerance in mitochondrial myopathy
• Severe, early ventilatory failure among SMA 

As the disease advances, other respiratory symptoms such as daytime respiratory insufficiency, ineffective coughing, airway clearance difficulties, and recurrent respiratory infections may emerge. It can even progress to respiratory failure and death in severe cases when there is no prompt respiratory management.^2,4 

Summary

Orthopnea, shortness of breath when lying flat, is a common and mostly the first noticeable respiratory distress among neuromuscular diseases (NMDs). It originates from the weakened respiratory muscles, typically the diaphragm and intercostal muscles, impairing chest wall mechanics and accessory muscle functions. A wide range of respiratory symptoms can be presented, such as shallow breathing, increased daytime fatigue, reduced lung capacity, and increased risk of respiratory complications. Management involves a comprehensive approach to physical (respiratory) therapy, postural modifications, and respiratory assistive devices, targeting medical interventions underlying NMDs. Hence, relieving orthopnea symptoms,  respiratory functioning requires improvement, whilst enhancing the quality of life among individuals with NMDs.  

FAQs 

What is paroxysmal nocturnal dyspnea (PND)? 

Paroxysmal nocturnal dyspnea (PND) is an awakening shortness of breath that only occurs during sleep, often after 1-2 hours of sleep. 

How are orthopnea and paradoxical breathing related in NMDs?

When respiratory muscles are weak, abnormal chest wall movements in paradoxical breathing can challenge the person with NMDs to breathe effectively when lying down. In turn, exacerbating orthopnea.