Despite significant differences in baseline characteristics by race, namely age, mechanism of injury (penetrating versus blunt), and in particular shock upon presentation to the ED and the number of units of PRBCs transfused, the incidence of ALI/ARDS was similar by race. In this study as well as in prior trauma studies, shock (10
) and transfusion of PRBCs (10
) are independent predictors for developing ALI/ARDS. Furthermore, the risk of developing ALI/ARDS increases as the number of units of PRBCs transfused increases (11
). Therefore, we expected that African-American patients would be more likely to develop ALI/ARDS.
One possible explanation for the similar incidence of ALI/ARDS by race is that the risk factors for developing ALI/ARDS were balanced between different races. For example, although African-American patients received the most units of PRBCs, they were also younger and therefore less likely to have co-morbidities. Co-morbidities may place patients at higher risk of developing ALI/ARDS (3
). Similarly, although Caucasian and Asian/Pacific Islander patients were older and therefore more likely to have co-morbidities they were less likely to present to the ED in shock and received fewer units of PRBCs. In addition to increasing co-morbidities with age, age itself is an independent risk factor for ALI/ARDS (12
). Our analyses are limited by not having the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores or co-morbidity data for each patient, which would have allowed us to control for these potential confounding factors.
Although our findings suggest that race does not contribute to the development of ALI/ARDS, it is well known that the etiology of ALI/ARDS is multigenic and multifactorial (13
). Recently, candidate genes for ALI/ARDS have been identified, replicated in independent populations, and clustered according to specific pathways involved in the development of ALI/ARDS (13
). The next step is to do genome wide association studies in which large numbers of single nucleotide polymorphisms (SNPs) are examined to detect associations between ALI/ARDS and known and previously unsuspected genes (14
Our investigation differs from prior studies of racial differences in ALI/ARDS in two important ways. First, other investigators focused on differences in mortality by starting with a cohort in which every patient had ALI/ARDS (3
). Therefore, these studies could not determine if there was a difference in the incidence of ALI/ARDS by race. In our study, by examining a cohort of 4,397 trauma patients, we determined that the incidence of ALI/ARDS was similar by race. Second, prior studies included heterogeneous samples of patients with ALI/ARDS due to a variety of causes (3
). Trauma patients with ALI/ARDS may differ from patients with ALI/ARDS secondary to other causes (5
). For example, patients with ALI/ARDS due to trauma have lower mortality rates than patients with ALI/ARDS due to sepsis (6
). In addition, the development of ALI/ARDS does not further increase the risk of death in trauma patients (16
). Moreover, studies have shown that there is less epithelial and endothelial cell injury, the hallmark of ALI/ARDS, in trauma patients with ALI/ARDS than in patients with ALI/ARDS from other causes (6
). Our findings provide further evidence suggesting that trauma patients with ALI/ARDS may be fundamentally different than non-trauma patients with ALI/ARDS. Considering this mounting evidence, perhaps clinical studies of patients with ALI/ARDS should consider only enrolling subgroups of patients with one cause of ALI/ARDS rather than enrolling such a heterogeneous patient sample. Conceivably, certain therapies for ALI/ARDS may be more effective for some subgroups of patients with ALI/ARDS than others.
Even within our sample of trauma patients with early ALI/ARDS secondary to major trauma, there may be heterogeneity. Early ALI/ARDS secondary to major trauma may differ in presentation, disease course and outcome depending on the nature, severity, and distribution of injuries. The most important distinction is direct lung injury from chest trauma versus indirect injury from abdominal trauma or extensive orthopedic fractures. Traumatic injury may be isolated to one body region, but more commonly, patients with severe trauma who are at greatest risk of developing ALI/ARDS present with injuries to multiple body regions. In some patients, the clinical picture may be further complicated by severe neurologic injury and neurogenic pulmonary edema.
In addition to major trauma, blood transfusions are another cause of ALI/ARDS in trauma patients. Blood transfusion is an independent risk factor for ALI/ARDS and can also lead to transfusion-related acute lung injury (TRALI). TRALI is defined as non-cardiogenic pulmonary edema associated with the transfusion of blood products (19
). According to the two-hit hypothesis of TRALI, trauma is recognized as a potential “first hit” as neutrophils are primed and adhere to the pulmonary endothelium. Transfusion of blood products delivers the “second hit” by activating the primed neutrophils, leading to TRALI (19
). TRALI is under diagnosed (20
) because diagnostic confirmation requires examining the donor and recipient for passively transfused antibodies (19
) which is not typically done. At our institution, only a few cases of TRALI have been reported to the blood bank over the 11-year period of this study. Therefore, we could not determine whether any patients in our cohort developed TRALI. Furthermore, some trauma patients with hemorrhagic shock receive numerous units of blood products and it would be difficult to differentiate trauma-related ALI/ARDS from TRALI in these patients.
The incidence of ALI/ARDS in our cohort was relatively low compared to some studies of trauma patients with an ICU admission (11
) but was consistent with one study (10
). The incidence of ALI/ARDS cited in clinical studies varies according to the cohort under investigation. For example, one study only included intubated patients whose Injury Severity Score was ≥16; the incidence of ARDS in this cohort was 34% (11
). Our cohort included all trauma patients who spent a portion of their hospitalization in the ICU soon after presentation to the ED. Therefore, we included patients with a greater range of injury severity scores; who may or may not have required mechanical ventilation. Furthermore, in our study, a single investigator identified patients with ALI/ARDS prospectively over the entire 11-year period. This investigator excluded patients who may have originally met the American-European Consensus Conference criteria for ALI/ARDS if a follow-up chest radiograph within the next 24 hours no longer showed bilateral infiltrates or if the PaO2
increased to >300. Even if the incidence of ALI/ARDS were underestimated in our cohort, it would not affect our ability to determine whether the incidence of ALI/ARDS differs by race because cases of ALI/ARDS would be similarly underestimated within each race.
There are some limitations to our study. First, although this cohort included patients over an 11-year period, it was done at only one major trauma center. This may limit the external validity of our findings. However, a strength of our single center study is that San Francisco General Hospital, the only designated level I trauma center in the city of San Francisco, has the ideal population for this type of study given the racial and ethnic diversity of its patients. Each of the major races was well represented in this study. Second, among the 219 patients who developed ALI/ARDS only 23% died. This small number of patients limits our ability to determine the predictors of mortality in this group because we would be at risk of committing a type II error.