Acute Lung Injury
Acute Lung Injury (ALI) is a severe clinical syndrome characterized by acute onset of hypoxemia, non-cardiogenic pulmonary edema, and widespread inflammation in the lungs. The pathogenesis of ALI involves disruption of the alveolar-capillary barrier, leading to increased vascular permeability and influx of protein-rich fluid into the alveolar spaces. This process is primarily driven by an exaggerated inflammatory response, often triggered by direct pulmonary insults such as pneumonia or aspiration, or indirect insults like sepsis, trauma, or pancreatitis. Neutrophil activation, release of pro-inflammatory cytokines, and endothelial and epithelial cell injury play central roles in the development of ALI. The resulting impairment of gas exchange, decreased lung compliance, and increased intrapulmonary shunt contribute to the clinical manifestations of respiratory distress and hypoxemia. ALI significantly impacts patient health, with high morbidity and mortality rates, prolonged hospital stays, and risk of progression to Acute Respiratory Distress Syndrome (ARDS), a more severe form of the disease. Survivors may experience long-term pulmonary dysfunction, reduced quality of life, and psychological sequelae.
Direct acute lung injury refers to cases where the primary insult occurs within the lung parenchyma itself. Common causes include pneumonia, aspiration of gastric contents, pulmonary contusion, inhalational injury, and near-drowning. The pathophysiology involves direct damage to the alveolar epithelium, leading to local inflammatory responses, increased capillary permeability, and alveolar flooding. Clinical manifestations often develop rapidly after the inciting event and may be more localized initially, depending on the nature and extent of the injury.
Indirect acute lung injury arises from systemic processes that secondarily affect the lungs, despite the initial insult occurring elsewhere in the body. The most frequent causes are sepsis, severe trauma, multiple transfusions, pancreatitis, and shock. Indirect injury is primarily mediated by circulating inflammatory mediators that activate and damage the pulmonary endothelium, resulting in diffuse microvascular injury, increased permeability, and non-cardiogenic pulmonary edema. This type often presents with more diffuse and bilateral lung involvement and may be associated with multi-organ dysfunction.
Acute Lung Injury affects a substantial proportion of critically ill patients worldwide. The incidence of ALI is estimated to range from 22 to 86 cases per 100,000 person-years, with considerable variation depending on diagnostic criteria and population studied. ALI and its severe form, ARDS, occur more frequently in adults but can also affect pediatric populations. The syndrome is most commonly seen in intensive care units, particularly among patients with sepsis, pneumonia, or major trauma. Mortality rates for ALI historically ranged from 30% to 40%, though advances in supportive care have led to modest improvements. Certain populations, such as the elderly and those with chronic comorbidities, are at higher risk of poor outcomes. Long-term survivors may have persistent physical and psychological impairments, underscoring the substantial public health burden of ALI.
The diagnosis of Acute Lung Injury is based on a combination of clinical, radiological, and laboratory findings. Key diagnostic criteria include acute onset of respiratory symptoms, bilateral infiltrates on chest imaging consistent with pulmonary edema, and hypoxemia defined by a reduced ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2), typically less than 300 mmHg. Importantly, the pulmonary edema must not be fully explained by cardiac failure or fluid overload, which is often assessed through clinical evaluation, echocardiography, or measurement of pulmonary artery wedge pressure. Additional diagnostic workup may involve exclusion of alternative causes of acute respiratory failure, assessment of risk factors or predisposing conditions, and laboratory tests to evaluate for infection, inflammation, or organ dysfunction. Early recognition and prompt differentiation from other causes of respiratory distress are critical for appropriate management.
Sivelestat sodium hydrate is available as a therapeutic option for the management of acute lung injury. This agent is administered to patients to address the underlying inflammatory processes associated with ALI, aiming to mitigate lung tissue damage and improve respiratory function.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
 | sivelestat sodium hydrate (Prop INNM; USAN) | 201677-61-4 | C20 H21 N2 O7 S . Na . 4 H2 O | 528.506 |
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