Chest
Volume 131, Issue 2, February 2007, Pages 554-562
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Recent Advances in Chest Medicine
Epidemiology and Outcomes of Acute Lung Injury

https://doi.org/10.1378/chest.06-1976Get rights and content

Abstract

Acute lung injury (ALI) and its presentation with more severe hypoxemia, the ARDS, is a challenging entity for clinical investigation because, like many critical illness syndromes, it lacks an accepted diagnostic test and relies on a constellation of clinical findings for diagnosis. Despite these barriers, there have been important advances in the clinical and population epidemiology of ALI. This article will review recent studies of the incidence, diagnosis, etiologic and prognostic factors, relevant disease subsets, mortality, and long-term outcomes of ALI. A detailed understanding of the epidemiology and outcomes of ALI is essential for future research on mechanisms of both the acute presentation and long-term sequelae, for designing studies to identify genetic risk factors for developing ALI, and to develop strategies to treat or prevent the morbidity encountered by survivors.

Section snippets

Diagnosis And Definition

ARDS is a syndrome that is diagnosed by the presence of a constellation of clinical criteria consisting of acute hypoxemic respiratory failure with bilateral radiographic opacities that may coexist with, but is not fully explained by, hydrostatic pulmonary edema. The terminology around ARDS became somewhat more confusing when the North American European Consensus Conference (NAECC) broadened the definition to include patients with milder hypoxemia.2ALI includes patients with less severe

Incidence

Two factors make studies of the epidemiology of ALI difficult. First, problems with the reliability of the diagnosis and inaccuracy of administrative coding make population-based epidemiology expensive and difficult because careful quality control and prospective validation of cohorts is necessary. Second, since ALI is a critical illness and requires arterial blood gases and chest radiographs for diagnosis, and since patients are cared for in ICUs, the epidemiology of the syndrome is

Risk and Prognostic Factors

Review articles on ALI list dozens of potential risk factors for ALI including drugs, burns, inhalation injury, pancreatitis, amniotic fluid embolism, and transfusion. In most cohort studies and clinical trials, the majority of cases are caused by pneumonia followed by extrapulmonary sepsis, and finally trauma. Studies of risk factors for ALI are limited by varying degrees of rigor in establishing the definition for the risk factor. These studies are challenging because they require not only

Disease Subsets

Arguments over whether ALI related to transfusion, direct lung injury, indirect lung injury, or the time course of presentation constitute fundamentally different diseases or not are longstanding.35Various reports36have suggested that direct (pneumonia, aspiration, contusion) and indirect (sepsis, trauma, drug overdose) causes of ALI result in characteristic radiographic and physiologic presentations. The findings are not consistent and fail to account for common scenarios with multiple risk

Genetic Epidemiology

The field of genetic epidemiology of ALI is in its infancy.39It is important to remember the advice of a review article40on genetic epidemiology, “Use of standardized, reproducible [phenotype descriptions] with strict requirements for training, certification, and quality control is a fundamental principle of population-based research that needs to be translated to genetic epidemiologic studies.” Genetic, genomic, and proteomic evaluations of complex illnesses like ARDS rely on a mature clinical

Mortality

Several observations on the mortality of patients with ALI appear consistent. The mortality rates of patients who present with ALI (Pao2/Fio2ratio < 300 mm Hg) and those who present with ARDS (Pao2/Fio2ratio < 200 mm Hg) are similar and from 35 to 40%. Mortality after ALI is declining in recent years, although the explanation for this is not completely clear.41, 42Patients appear to die with ALI or from complications of their underlying risk factor as opposed to dying from unsupportable

Outcomes After ALI and ARDS

The literature on long-term outcomes after ALI and ARDS has evolved significantly over recent years. As more investigators have studied outcomes after lung injury, several robust observations have emerged. Most studies suggest that the major long-term consequences of lung injury are related to neuromuscular, cognitive, and psychological dysfunction rather than pulmonary dysfunction (Table 2). It is ironic that the organ systems that have the greatest impact on functional and quality of life

Health-Related Quality Of Life

There are currently 13 studies (n = 557) that have evaluated health-related quality of life (HRQL) in survivors of ALI, and the findings of these studies have been recently summarized in a metaanalysis by Dowdy et al,46who stratified their analysis by whether authors reported Short Form-36 as the HRQL outcome measure. Five of these studies (n = 330) used the Short Form-36; these results were pooled and showed that all eight domains were below the age- and sex-matched population normal. The mean

Physical Disability: Long-term Pulmonary Sequelae

The findings from early case series to more recent prospective cohort studies are consistent and suggest that the majority of patients do not have significant long-term pulmonary dysfunction after lung injury. Most studies47, 48, 49have noted a persistent reduction in diffusion capacity, which does not appear to be of important functional consequence. Neff and colleagues50reviewed 30 studies that evaluated pulmonary function in ARDS survivors, and reported significant variability in the

Physical Disability: Musculoskeletal Sequelae

Survivors of ALI have persistent functional limitation captured as a decreased distance walked in 6 min. At 1 year and 2 years after ICU discharge, ARDS survivors had evidence of muscle wasting and weakness and could achieve only 66% of their predicted exercise capacity.47, 48The precise determinant(s) of this long-term exercise limitation remains unclear, but possible contributors may include critical illness-related neuromuscular disease, entrapment neuropathies, and heterotopic ossification.

Neuropsychological Disability: Emotional Function After ARDS

Psychiatric or emotional morbidity following ALI includes depression, anxiety, and posttraumatic stress disorder (PTSD).53It is still unclear whether emotional disorders constitute a psychological reaction to profound emotional and physiologic stress are a consequence of direct brain injury sustained from ALI and its treatment, or a combination of these. The prevalence and severity of these mood disorders are variable and may also change over time. Hopkins and colleagues54evaluated depression

Neuropsychological Disability: Cognitive Impairment in ARDS Survivors

Hopkins and colleagues59published the seminal long-term cognitive outcome study in ARDS survivors in 1999. In this natural history cohort, they found that 100% of ARDS survivors had cognitive impairments at the time of hospital discharge. At 1-year follow-up, 30% of the survivors had decreased intellectual function and 78% had impaired memory, attention, concentration, and/or mental processing speed. At 2-year follow-up of this same patient cohort, 47% had neurocognitive impairments with no

Caregiver and Financial Burden After Critical Illness

As more patients are surviving critical illness and are discharged from hospital more quickly, the burden of caregiving has shifted to family members. In the United States, 31% of families report a loss of most or all of their savings.60Challenges for the caregiver begin during the ICU stay where they may experience overwhelming stress and distress. Azoulay and colleagues61reported that posttraumatic stress symptoms consistent with a moderate-to-major risk of PTSD were found in 33% of ICU

Conclusions

ALI is no longer a disease of specialty interest to the pulmonologist and intensivist at academic centers. Research suggests that it is common, lethal, underrecognized, treatable and, for survivors and their caregivers, a source of significant ongoing impairment. Ongoing research activities to improve the reliability and validity of diagnostic criteria for ALI, genetic risk factors, mechanisms of long-term impairment, and interventions to prevent or treat the sequelae of ALI will hopefully

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    The authors have no conflicts of interest to disclose.

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