<aside>
Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). It represents widespread injury to the alveolar-capillary interface, resulting in non-cardiogenic pulmonary edema, alveolar collapse, and impaired gas exchange.
</aside>
| Category | Examples |
|---|---|
| Infectious | Severe viral pneumonia (e.g. COVID-19, influenza), sepsis |
| Toxic inhalation | Smoke, chemical fumes (e.g. chlorine, nitrogen dioxide) |
| Systemic illness | Sepsis, pancreatitis, trauma, burns |
| Drug-induced | Amiodarone, chemotherapy agents (e.g. bleomycin), radiation |
| Aspiration | Gastric contents causing chemical pneumonitis |
| Transfusion reaction | TRALI (transfusion-related acute lung injury) |
| Autoimmune | Vasculitis (e.g. GPA), connective tissue disease (e.g. dermatomyositis) |
DAD progresses through two major histological phases:
| Phase | Timing | Key fetures |
|---|---|---|
| 1. Exudative Phase | Days 1–7 | • Alveolar edema (protein-rich), hyaline membrane formation |
| • Type I pneumocyte necrosis | ||
| • Neutrophilic infiltration | ||
| 2. Organizing (Proliferative) Phase | After 1 week | • Type II pneumocyte hyperplasia |
| • Interstitial fibroblast proliferation | ||
| • Potential for fibrosis (fibrotic phase) |
Progression of disease in ARDS: The clinically challenging problem of ARDS is illustrated by the diversity in the underlying etiologies and the complex time course of the disease. Approximately 40% of patients with severe sepsis will develop ARDS. Patients who do not recover during the proliferative phase may go on to develop emphysematous regions in the lungs and ultimately fibrosis. While it is reasonable to expect that each of these phases will have a distinct metabolomics phenotype, these have yet to be realized.
"Lungs diagram simple" by Patrick J. Lynch, medical illustrator. Licensed under CC BY 2.5 via Wikimedia Commons – http://commons.wikimedia.org/ wiki/File:Lungs_diagram_simple.svg#mediaviewer/File:Lungs_diagram_simple.svg.
| Feature | Details |
|---|---|
| Acute onset respiratory failure | Within 1 week of known insult |
| Hypoxemia | PaO₂/FiO₂ ≤ 300 mmHg (Berlin definition of ARDS) |
| Bilateral infiltrates on imaging | Not fully explained by effusion, atelectasis, or nodules |
| Non-cardiogenic cause | No evidence of left atrial hypertension or fluid overload |
DAD is a histological diagnosis, but suggested by:
Microscopic findings in lung tissue in patients with ARDS: In acute respiratory distress syndrome (ARDS), features of diffuse alveolar damage (DAD), such as in the acute ‘exudative’ phase (~7 days) (panel a), are typically followed by alveolar type II (ATII) cell hyperplasia and interstitial fibrosis in a ‘proliferative’ phase. Eosinophilic depositions termed hyaline membranes are defining features of DAD (pink structure lining the central alveolus, indicated by the arrowhead in panel b) are defining features of DAD. Leukocytes are embedded in the hyaline membranes (arrows in panel b). Electron microscopic analyses (panel c) demonstrate that alterations in endothelial and epithelial cells are critical features of acute alveolar injury in ARDS. Focal epithelial destruction of alveolar type I (ATI) cells and denudation of the alveolar basement membrane occur early in ARDS, whereas endothelial continuity is preserved with modest alterations in most cases. The pattern shown in panel c was identified in the lungs of a patient with indirect acute lung injury resulting from sepsis.
A, alveolar space; BM, basement membrane; C, capillary; EC, erythrocyte; EN, endothelial cell; HM, hyaline membrane; LC, leukocyte. Matthay, M. A. & Zimmerman, G. A. (2005) Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am. J. Respir. Cell Mol. Biol. 33, 319–327. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
