Diffuse alveolar damage


Diffuse alveolar damage is a histologic term used to describe specific changes that occur to the structure of the lungs during injury or disease. Most often DAD is described in association with the early stages of acute respiratory distress syndrome. It is important to note that DAD can be seen in situations other than ARDS and that ARDS can occur without DAD.

Definitions

  1. Timing: onset of respiratory symptoms within one week of a injury/insult.
  2. Chest Imaging: either chest x-ray or CT scan, must show bilateral opacities that cannot be fully explained by other conditions such as effusion, lung/lobar collapse, or lung nodules.
  3. Origin of Edema: respiratory failure that cannot be fully explained by cardiac failure or fluid overload, this needs objective assessment such as an echocardiogram.
  4. Impaired Oxygenation: this can be determined by looking at the ratio of arterial oxygen tension to fraction of inspired oxygen that can be obtained based on an arterial blood gas test. Note: all PaO2/FiO2 ratios used in the determination of the severity of ARDS require that the patient be on a ventilator at a setting that includes 5 cm H2O or more of positive end-expiratory pressure or continuous positive airway pressure.
Level of ARDSPaO2/FiO2 RangePEEP/CPAP
Mild ARDS201-300≥5 cm H2O
Moderate ARDS101-200≥5 cm H2O
Severe ARDS<100≥5 cm H2O

Histology/Progression

The epithelial lining of alveoli are composed of two different types of cells. Alveolar type I epithelial cells comprise about 80% of the alveolar surface area and are primarily responsible for gas exchange. Alveolar type II epithelial cells play the critical roles of producing surfactant, moving water out of the airspaces, and regenerating alveolar epithelium. The alveolar type II epithelial cells are more resistant to damage, so after an insult to the alveoli, most of the damage will occur to the alveolar type I epithelial cells.
Once the initial insult has damaged the alveoli and begun the process of DAD, the condition will typically progress in three phases: exudative, proliferative, and fibrotic. Below are the description of the phases, paraphrased from Sweeney et al.
It is important to note that DAD can occur in settings other than ARDS and that ARDS can occur with histology other than DAD. That being said, the histologic finding of DAD is often associated with the clinical syndrome ARDS but it can also be seen in conditions such as acute interstitial pneumonia, acute exacerbation of idiopathic pulmonary fibrosis, and primary graft dysfunction after lung transplant. The most common causes of ARDS are pneumonia, non-pulmonary sepsis, and aspiration.
To reiterate, the hallmark of DAD is hyaline membrane formation. There is an similar process which occurs in newborns called hyaline membrane disease, although the preferred term is surfactant-deficiency disorder, that also has the formation of hyaline membranes. This disorder typically develops due to prematurity, especially when the infant is delivered prior to 36 weeks since surfactant doesn't start being produced till 35 weeks gestation. The lack of surfactant causes alveolar collapse and subsequent damage to the epithelial lining of the alveoli, causing the same path of damage described in the above section.

Diagnosis

In order to make a diagnosis of DAD a biopsy of the lung must be obtained, processed, and examined microscopically. As described above, the hallmark of diagnosing DAD is the presence of hyaline membranes. Most frequently DAD is associated with ARDS, but since there are clinical criteria upon which we can diagnose ARDS, it is often unnecessary in all cases to obtained invasive biopsies of the lung. Additionally, there are limitations of the biopsy test since it is possible to sample a potentially normal area of lung even though there is DAD in the rest of the lung, resulting in a false negative.

Treatment

The most important factor for treating DAD or ARDS is to treat the underlying cause of the injury to the lungs, for example pneumonia or sepsis. These patients will have problems with oxygenation, meaning they will likely need a breathing tube, medications to keep them comfortable, and a mechanical ventilator to breath for them. The mechanical ventilator will often be set to a setting of at least 5 cm H2O of positive end-expiratory pressure to keep the alveoli from collapsing during exhalation. Other treatments to improve oxygenation may include prone positioning or extracorporeal membrane oxygenation.

Prognosis

As expected, the mortality rates increase as the severity of the ARDS increases with mortality rates at approximately 35%, 40%, and 46% for mild, moderate, and severe, respectively. It has been revealed that patients with ARDS that show DAD on histology are at a high mortality rate of 71.9% compared to 45.5% in patients with ARDS but without DAD. Of the patients who succumb to ARDS, the most common cause of death is septic shock with multi organ dysfunction syndrome.
Among survivors upon discharge, many will have impairments in their lung function. The majority of patient will have decrease diffusion capacity while fewer patients will have issues with airflow. These airflow issues will typically resolve within six months and the diffusion issues will resolve within five years.