Incidence and Risk Factors of Pneumothorax in Patients With Neuromuscular Diseases

Neuromuscular diseases (NMDs) can cause respiratory muscle weakness, leading to mechanical failure of the respiratory pump. As the disease progresses, patients are exposed to multiple respiratory complications, ranging from sleep disturbances and daytime fatigue, related to sleep disruption caused by alveolar hypoventilation, to pneumonia and acute respiratory failure, which may be life-threatening.

The standard treatment for this respiratory failure is long-term mechanical ventilation, which is recommended for patients with neuromuscular diseases by the French National Authority for Health (Haute Autorité de Santé, HAS) and by the various National Diagnostic and Care Protocols. Depending on the severity of the disease and the progression of respiratory symptoms, mechanical ventilation may be used either at night or both during the night and the day. Since the second half of the 20th century, mechanical ventilation has been the standard treatment for restrictive respiratory failure of neuromuscular origin. This treatment, which provides respiratory pump support, has improved survival in these patients, sometimes by several decades, as observed in Duchenne muscular dystrophy. This treatment, used both for acute respiratory failure in intensive care settings and for chronic restrictive respiratory failure of non-parietal origin, is delivered through the application of positive inspiratory pressure, either invasively or non-invasively.

However, the management of these patients is not limited to mechanical ventilation. Other devices delivering positive pressure are also used. Respiratory muscle involvement also affects patients' ability to cough and clear airway secretions, thereby increasing the risk of respiratory tract infections and secretion retention. In this context, mechanical cough-assist devices are used to improve patients' airway clearance capacity. These devices are mechanical insufflation-exsufflation systems that apply positive pressure during inspiration to increase the insufflated volume, followed by negative pressure to generate an increased expiratory flow capable of facilitating secretion clearance. This treatment has become a particularly important component of the management of these patients, who are especially vulnerable to respiratory infections.

Finally, pediatric patients face an additional challenge, as respiratory pump failure may impair lung and thoracic growth, particularly when disease progression occurs during the first years of life. In the absence of specific intervention, this may lead to chest deformities (for example, a "pear-shaped" thorax in infants with spinal muscular atrophy due to underdevelopment of the pulmonary apices and/or scoliosis of varying severity. Orthopedic deformities combined with respiratory muscle weakness lead to restrictive respiratory failure before the end of growth, requiring specific respiratory management including non-invasive ventilation (NIV) with high pressure levels . Daily lung hyperinflation sessions performed using pressure insufflation devices are also proposed to promote thoracic and pulmonary growth.

The use of these different types of devices (mechanical ventilation, mechanical insufflation-exsufflation devices, etc.) is associated with well-known complications, particularly the risk of barotrauma related to increased intrathoracic pressure during inspiration, which may expose patients to the risk of pneumothorax. The occurrence of such complications may be promoted by patient-related intrinsic factors, including underlying conditions such as chronic obstructive pulmonary disease (COPD), interstitial lung disease, or acute respiratory distress syndrome (ARDS), but may also be related to ventilation settings. Data on the complications of mechanical ventilation affecting the pulmonary parenchyma have been available for several decades, both from animal and human studies. However, these studies have mainly focused on acute ventilation in the context of the management of acute respiratory distress syndrome.

In contrast, there are very few data on these complications in the context of chronic respiratory failure treated with mechanical ventilation, which is the standard treatment for respiratory failure of neuromuscular origin. No prospective study has investigated this population to determine the incidence of barotrauma-related complications. The only reports identified in the literature are isolated case reports describing the occurrence of pneumothorax in patients with Duchenne muscular dystrophy, amyotrophic lateral sclerosis, congenital nemaline myopathy , and Ullrich muscular dystrophy . These data do not allow investigators to determine whether there is an increased risk associated with positive-pressure respiratory support or whether specific diseases are at greater risk of developing pneumothorax. Furthermore, given the rarity of these diseases and their long-term course, conducting a prospective study involving a sufficiently large population of patients with neuromuscular diseases would be difficult.

The availability of access to data warehouses provides a new opportunity to address this question. The investigators aim to conduct a study using the AP-HP Health Data Warehouse (Entrepôt de Données de Santé, EDS) to analyze the prevalence of pneumothorax in a large population of patients with neuromuscular diseases and to assess its association with positive-pressure respiratory treatments, including mechanical ventilation, cough-assist devices (such as mechanical insufflation-exsufflation devices), and thoracic mobilization through lung hyperinflation (using pressure insufflation devices).

Working with data from the EDS would increase the statistical power of the sample. The vast majority of these patients receive multidisciplinary care in the neuromuscular rare disease reference centers within the FILNEMUS network. In the Île-de-France region, the six constituent centers of the neuromuscular rare disease reference center are located within the AP-HP (Pediatric centers: Trousseau, Necker, Raymond Poincaré; Adult centers: Pitié-Salpêtrière, Raymond Poincaré, Henri Mondor). The use of the AP-HP EDS will make it possible to analyze a large cohort capable of providing answers to these unresolved questions.

The investigators aim to determine the prevalence and frequency of pneumothorax in patients with neuromuscular diseases using these medical devices, and hypothesize that this prevalence is not higher than that observed in the general population.

The investigators also hypothesize that certain neuromuscular diseases, due to their pathophysiological characteristics, are associated with a higher risk of developing this type of adverse event.

Finally, exposure to mechanical ventilation and/or cough-assist devices and/or thoracic mobilization devices is hypothesized to be associated with an increased risk of pneumothorax. This study will provide objective data regarding the theoretical risk of a serious complication associated with respiratory devices that are widely prescribed in patients with neuromuscular diseases. If this study demonstrates that pneumothorax is a complication associated with neuromuscular diseases, it may encourage clinicians to monitor their patients more specifically by identifying those with disease-related risk factors. The results of this study will help guide the prescription of respiratory devices and allow the settings used to be adapted according to individual patient risk. Identifying neuromuscular diseases that are specifically associated with an increased risk of pneumothorax during respiratory support will make it possible to identify patients requiring specific adjustments and contribute to the appropriate prescription of these treatments. Identification of contributing risk factors may help limit the pressure levels prescribed in order to reduce the risk of complications.

The use of EDS data in the field of rare diseases represents an innovative approach to addressing unresolved clinical questions in these conditions, making it possible to collect a large amount of data over several years of follow-up. This represents a major asset for improving knowledge of these low-prevalence diseases, both in terms of determining their natural history and studying the consequences of their treatments.