Published ahead of print on December 18, 2002, doi:10.1164/rccm.200206-542OC
© 2003 American Thoracic Society
Pulmonary Function and Health-related Quality of Life in Survivors of Acute Respiratory Distress SyndromeDepartment of Medicine, Pulmonary and Critical Care Divisions, LDS Hospital; Department of Medicine, Pulmonary and Critical Care Divisions, University of Utah, Salt Lake City; Psychology Department and Neuroscience Center, Brigham Young University, Provo; and Statistical Data Center, LDS Hospital, Salt Lake City, Utah Correspondence and requests for reprints should be addressed to James F. Orme Jr., M.D., Division of Critical Care Medicine, LDS Hospital, 8th Avenue and C Street, Salt Lake City, UT 84143
Although survival rates for acute respiratory distress syndrome have increased, there is only limited information regarding the quality of life and the relationship between quality of life and pulmonary function after survival. We prospectively measured pulmonary function, emotional function, and health-related quality of life in a cohort of acute respiratory distress syndrome survivors recruited from patients who were enrolled in a randomized clinical trial of high versus low tidal volume mechanical ventilation at 1 year after their recovery. No significant differences were found between the patients treated with high and low tidal volumes on any pulmonary function measure. Approximately 80% of the patients in both groups demonstrated reduced diffusing capacity; 20% had airflow obstruction, and 20% had chest restriction. Scores on measures of depression and anxiety were within the normal ranges, suggesting that they did not have significant affective symptoms. However, both groups reported decreased health-related quality of life in physical functioning, physical ability to maintain their roles (role-physical), bodily pain, general health, and vitality (energy) on the Medical Outcome Study Short Form Health Survey with similar physical limitations reported on the Sickness Impact Profile questionnaire. The pulmonary function abnormalities correlated with decreased health-related quality of life for domains reflecting physical function. Acute respiratory distress syndrome survivors treated with high and low tidal volumes have abnormal pulmonary function that was related to decreased health-related quality of life 1 year after hospital discharge.
Key Words: acute respiratory distress syndrome • pulmonary function • quality of life Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury, arterial hypoxemia, reduced total thoracic compliance, and diffuse bilateral infiltrates on chest radiograph due to increased-permeability pulmonary edema (1, 2). Treatment of ARDS requires aggressive supportive care, including positive pressure ventilation and increased oxygen concentrations with risks of barotrauma, oxygen toxicity, and nosocomial infection. Survivors of ARDS are often left with chronic pulmonary fibrosis, reduced pulmonary function, and diminished health-related quality of life (3–14). ARDS patients have been traditionally ventilated with tidal volumes of 10–15 ml/kg (15, 16). These tidal volumes are larger than those in healthy, spontaneously breathing adults but have been considered necessary to maintain adequate ventilation and oxygenation. However, up to one-third of the lung may be normally aerated during ARDS (17). High inspiratory pressures with high tidal volumes (HTVs) in these spared regions can overdistend alveoli, disrupt the alveolar–capillary membrane (17), and increase inflammation (18). Uncontrolled studies in the 1990s suggested that protecting normally aerated regions of the lung with small tidal volumes could reduce ARDS mortality (19, 20). Recent randomized controlled trials have yielded conflicting results. Several studies did not find reduced mortality with the use of low tidal volume (LTV) therapy (21–23). A multicenter trial involving 860 ARDS patients (PaO2/FIO2 less than 300 mm Hg) found that a LTV strategy resulted in improved survival and a shorter mechanical ventilation time (18). Increased survival with small tidal volumes raises questions regarding the effect of tidal volume on intermediate outcomes in ARDS survivors, including pulmonary function and quality of life. A LTV strategy may result in long periods of hypercapnea, hypoxemia, exposure to high FIO2, and tachypnea. Outcome studies of patients treated with traditional large tidal volumes have identified residual pulmonary function abnormalities (restriction, obstruction, and decreased carbon monoxide diffusing capacity (DLCO) (4–9). Other studies show reduced health-related quality of life in ARDS survivors (9–14). However, a small study (13 HTV patients and 7 LTV patients) found no difference in pulmonary function or health-related quality of life in patients studied 1 to 2 years after ARDS (3). The purpose of this study was to assess 1-year pulmonary dysfunction, the health-related quality of life, and their relationship in ARDS patients treated with HTVs versus LTVs. The patient cohort was enlisted from ARDS survivors who participated in a randomized, controlled HTV versus LTV mechanical ventilation trial.
Patient Selection The ARDS survivors from a randomized clinical trial of HTV versus LTV ventilation management were approached to participate in a 1-year outcome study to assess pulmonary function and health-related quality of life. This 1-year outcome study of pulmonary function and health-related quality of life was approved by LDS Hospital Institutional Review Board and conformed to institutional and federal guidelines for the protection of human subjects. Written informed consent was obtained from the patient before hospital discharge after treatment of ARDS. Seventy-eight consecutive ARDS survivors (33 HTV, 45 LTV) were evaluated for this study (Figure 1) ; 66 completed the 1-year evaluation (29 HTV, 37 LTV). Three survivors were excluded at the initial evaluation: two HTV patients (one with cognitive disability and one with Alzheimer's disease) and one LTV patient (cognitive disability) declined the study. Three ARDS survivors (all LTV) died in the first year after hospital discharge from one of the following: pulmonary fibrosis/cor pulmonale, liver failure, or diabetic complications. Five survivors (two HTV and three LTV) declined to return when contacted (e.g., busy schedules or not interested).
Eligible ARDS patients had been enrolled in the LTV versus HTV ventilation study. The inclusion criteria for the ventilation study were as follows: tracheal intubation, PaO2/FIO2 of 150 mm Hg or less, pulmonary wedge pressure of 18 mm Hg or less (when available), no clinical evidence of congestive heart failure, diffuse infiltrates in three out of four quadrants on chest radiographs, age of 16 years or more, and the presence of an ARDS risk factor. Patients were excluded if they had disease states that were not reversible (e.g., liver failure, malignancy, patients with acquired immune deficiency syndrome), traumatic brain injury, prior neurologic disease, and prior cognitive disability or if they were enrolled in another ARDS study. In the underlying low versus HTV study, patients assigned to the HTV group were treated with ventilation protocols that directed a conventional tidal volume in the range of 10–15 ml/kg predicted body weight based on actuarial data (mean tidal volume = 11.0 ml/kg) (24). Plateau pressure influenced tidal volume assignment within the range to maintain plateau pressure of less than 70 cm H2O. The patients assigned to LTV were ventilated with a target tidal volume range of 4–8 ml/kg (mean tidal volume = 7.7 ml/kg). Plateau pressure influenced tidal volume assignment to maintain plateau pressure of less than 40 cm H2O. The mean plateau pressure was 44 cm H2O for the HTV group and 32 cm H2O for the LTV group. The same computerized rules were used in both groups to maintain PaO2 above 55 mm Hg (mean PaO2: HTV = 72.1 mm Hg and LTV = 69.9 mm Hg) by adjusting FIO2 and positive end expiratory pressure. The mean FIO2 was 0.55 for the HTV group and 0.56 for the LTV group, and the mean positive end expiratory pressure was 8.3 cm H2O for both groups. Respiratory rate setting was adjusted to maintain the pH to 7.35 or more for the HTV group and 7.20 or more for the LTV group (25, 26).
Pulmonary Function
Health-related Quality of Life and Emotional Function
Data Management and Statistical Analysis Pearson's product moment correlations between measures of pulmonary function and health-related quality-of-life data were performed. For SIP and SF-36 scores, a sample of 29 HTV and 37 LTV patients has a 90% power to detect a difference of 0.93 SD (SIP) and 1.03 SD (SF-36) when testing at the two-sided 0.017 and 0.006 significant levels, respectively. Similarly, for pulmonary function, this sample has a 90% power to detect a difference of 1.03 SD when testing at the two-sided 0.006 significance level.
Descriptive statistics for the ARDS patients are presented in Table 1 . There were no significant differences in age, sex, or follow-up rate between the two groups of survivors. There were no significant differences in initial illness severity as measured by Acute Physiologic and Chronic Health Evaluation II score, LDS Hospital multiple organ failure score (35), PaO2/FIO2 ratio, or number of ARDS risk factors. Thirty-nine of the 66 patients reported a history of smoking.
Hospital data for the patients enrolled in the current long-term outcome study are shown in Table 2 . Tidal volume, plateau pressure, and respiratory rate were significantly different based on tidal volume strategy used. Other respiratory data variables, length of intensive care unit and hospital stay, and organ failure scores were not significantly different between the groups.
All 66 patients had follow-up spirometry at 1 year; 61 completed additional studies, including DLCO measurements, arterial blood gases, and total lung capacity. Pulmonary function was reduced in both groups, but there were no significant differences between them (Table 3) . Eighty percent of patients had a reduced DLCO, most often mild (46%) or moderate (23%). Obstructive and restrictive patterns were equally present in the HTV and LTV groups (approximately 20% for each). Of the 13 patients with obstruction, 11 (three of five HTV and eight of eight LTV) had a history of smoking when they were enrolled in the underlying HTV/LTV ventilation study.
The mean scores for the Beck Depression Inventory and Beck Anxiety Inventory were 9.3 ± 9.5 (range, 0 to 41) and 9.6 ± 9.8 (range, 0 to 43), respectively. These findings are not different from the normal population. However, 11 patients (16%) had scores above 16 on the Beck Depression Inventory and 16 patients (24%) on the Beck Anxiety Inventory, indicating moderate symptoms of depression and anxiety. All 66 patients completed the SF-36 questionnaire. Ten (n = 2 HTV and n = 8 LTV) were unable to complete the SIP questionnaire. Health-related quality-of-life scores are summarized in Table 4 . There were no significant differences between the HTV versus LTV groups for any category on either the SF-36 or SIP (Table 4). Both the SF-36 and SIP showed lower health-related quality of life than the normal population. Mean SF-36 scores were well below population norms in all domains except for social functioning, role-emotional, and mental health. The mean SIP scores were elevated for all three categories (Table 4).
Pulmonary function measures correlated with measures of health-related quality of life (Table 5) . The impaired physical abilities or physical complaints reported on the SF-36 and SIP questionnaires were significantly correlated with decreased lung volumes (total lung capacity, FVC, FEV1), DLCO, and PaO2.
Impaired health-related quality of life is common after recovery from ARDS (11–13). We observed no differences in pulmonary function or health-related quality-of-life in ARDS patients treated with two different ventilator strategies. ARDS survivors had significant reductions in health-related quality of life for physical functioning, role-physical, bodily pain, general health, vitality, and physical limitations similar to those observed in populations of patients with chronic illnesses and ARDS (9–11, 13, 14). Our ARDS survivors' health-related quality-of-life scores were the same as normal populations for social functioning, role-emotional, and mental health. These results suggest that the decreased health-related quality of life is related to physical rather than emotional or psychologic complaints. Our findings are similar to studies in which physical sequelae were significant factors in reduced health related-quality of life for ARDS survivors (9, 11). In contrast to previous studies, the emotional domains in our study did not correlate with pulmonary function (11, 14, 36, 37). Recent reports suggest that health-related quality of life may be adversely affected by emotional or psychological complaints. For example, Weinert and colleagues found that 43% of patients with acute lung injury report symptoms of depression (11), and Angus and colleagues reported depression and anxiety at 1 year in over 50% of their ARDS patients (36). Post-traumatic stress disorder (anxiety disorder) has been reported in ARDS survivors and related to decreased quality of life (14). Alternatively, we previously reported that ARDS survivors did not differ from normal subjects on mean SF-36 role emotional and mental health of the SF-36 and had normal scores for the Beck Depression and Anxiety Inventories (12). In addition, in this study, the ARDS survivors reported mild to moderate symptoms of depression (16%) and anxiety (24%) on the Beck Inventories that was not related to health-related quality of life. That is, there was no relationship between emotional domains and health-related quality of life. Conversely, lower health-related quality of life was related to the physical domains on the SF-36 and SIP. Our study confirms that ARDS survivors have significant pulmonary impairments (7, 8). Reduced pulmonary function was significantly correlated with impaired quality of life only in domains associated with physical health. Decreased lung volume and DLCO had the strongest correlations. The absence of a correlation between airflow obstruction and health-related quality of life may be explained by the small number of subjects (n = 13) with obstruction. Similar findings were reported by Schelling and coworkers in a cohort of 50 long-term ARDS survivors (37). At a median follow-up of 5.5 years after ARDS, they found that a majority of the patients had pulmonary function abnormalities (20% had low total lung capacity, and 4% had abnormal forced vital capacity; none had severe airflow limitation). Patients with pulmonary function impairments had the lowest SF-36 scores, and those who had mild respiratory distress at rest or dyspnea on exertion scored lower in all SF-36 domains, physical and emotional. Low participation rate and the nonuniform follow-up time interval limit the study (37). In contrast, a recent study found that decreased quality of life was more frequently associated with general health rather than lung problems measured by a lung-related SIP score or pulmonary function abnormalities in ARDS survivors (9). Ghio and colleagues surveyed 25 ARDS survivors, and 50% reported respiratory complaints, including dyspnea, cough, or wheeze (7). Using a pulmonary disease-specific measure of health-related quality of life, Davidson and colleagues found impaired health-related quality of life correlated with dyspnea and cough in ARDS patients (13). As in the Davidson and colleagues' study, we found that ARDS survivors had both pulmonary symptoms and nonrespiratory health complaints (13). The nonrespiratory complaints in our patients included movement limitations due to generalized weakness, traumatic limb fractures, and/or peripheral nerve injury. Our ARDS patients also reported frequent dyspnea, especially on exertion. Dyspnea on exertion may reflect impaired pulmonary function, muscle weakness, cardiac problems, or all of the above. The patients may perceive increased work in breathing on exertion because of muscle weakness when pulmonary function is not impaired. Herridge reported significant weight and muscle loss that resulted in debilitation, and heterotopic ossification impaired patients' ability to exercise (39, 40). Muscle weakness itself may contribute to reduced health-related quality of life on the physical domains reported in our ARDS patients. Exercise testing and respiratory-specific measures of quality of life may help to determine the contributions of pulmonary and nonpulmonary factors to long-term health-related quality of life. The strengths of our study include prospective design, consistent follow-up time, and high follow-up rate. The 1-year follow-up rate was 89% and 93% if the patients who died are excluded. The relationship between pulmonary function abnormalities and decreased health-related quality of life in our study does not appear to be due to subject selection bias. The limitations of the study include the small sample size and the lack of an appropriate non-ARDS control group. The three patients who died during the first year were all in the LTV group. However, only one patient died from lung disease; therefore, it is unlikely that these three deaths influenced our results. The patients in our study in the LTV group were ventilated with slightly larger tidal volumes compared with the ARDS Network study (18) but lower than traditional tidal volumes. It is unclear whether ARDS patients treated with lower tidal volumes than those used in our study would have different pulmonary function or health-related quality of life outcomes. In addition, we did not assess other outcome variables that may affect pulmonary function or health-related quality of life. For example, exercise testing and oximetry could be used to assess the impact of exercise on pulmonary function. Measures of cognitive function (12), neuromotor function (38, 39), and post-traumatic stress disorder (14) might elucidate other factors that influence quality of life. In summary, ARDS survivors treated with HTV versus LTV ventilation were not different due to the type of ventilation on measures of pulmonary function or health-related quality of life at 1-year follow-up. The ARDS survivors had pulmonary function abnormalities, notably reduced DLCO, and restrictive and/or obstructive patterns, as well as reduced health-related quality of life. The reduced quality of life was related to physical rather than emotional or mental health concerns and is similar to that observed in ARDS and other chronic illness populations. ARDS survivors treated with high and LTVs have abnormal pulmonary function that was related to decreased health-related quality of life one year after hospital discharge.
The authors are indebted to C. Greg Elliott for his review of this article.
Supported by Deseret Foundation Grants #300 and #318 and National Institutes of Health ARDS SCOR Grant #HL50513. Received in original form June 10, 2002; accepted in final form December 6, 2002
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