Survivors Of Acute Lung Injury Research Articles

Comparative Study of Acute Lung Injury in COVID-19 and Non-COVID-19 Patients

Background: Amid the coronavirus disease 2019 (COVID-19) pandemic, we analyzed clinical characteristics of acute lung injury (ALI) in COVID-19 patients and reported their similarity and dissimilarity to those of non-COVID-19 patients in the intensive care unit (ICU).Methods: We reported on 90 COVID-19 and 130 non-COVID-19 ALI patients in the ICUs of multiple centers. Demographic data, medical histories, laboratory findings, and radiological images were analyzed and compared between the two cohorts and within each cohort between survivors and non-survivors. For ALI survivors, clinical characteristics before and after treatment were also compared.Findings: Aberrations in blood parameters, such as leukocytosis, neutrophilia, and thrombocytopenia, were observed in both cohorts. More characteristic abnormalities, including significantly higher red cell distribution width (RDW), C-reactive proteins, and lactic dehydrogenase (LDH) but lower troponin (TnT) and procalcitonin, were observed in the COVID-19 cohort than in the non-COVID-19 cohort, whereas D-dimer levels showed a similar elevation in both cohorts. The COVID-19 cohort also showed more diversified CT patterns where severe features such as consolidations and crazy paving patterns were more frequently observed. Multivariate analysis indicated that age, fever symptom, prothrombin time, procalcitonin, partial pressure of carbon dioxide, oxygenated hemoglobin, and crazy paving patterns in CT scans were independent risk factors associated with COVID-19.Interpretation: Comparison of ALI characteristics between COVID-19 and non-COVID-19 patients in the ICU setting provided insight into the pathogenesis of ALI induced by different risk factors, suggesting distinct treatment plans.

Survivors of Acute Lung Injury Have Greater Impairments in Strength and Exercise Capacity Than Survivors of Other Critical Illnesses as Measured Shortly After ICU Discharge.

To compare the physical function on ICU discharge in adults who survived an ICU admission for acute lung injury (ALI) with those admitted for a critical illness other than ALI. Two groups were recruited, (i) those who survived an ICU admission for ALI and, (ii) those who survived an ICU admission for a critical illness other than ALI. Within 7 days of discharge from ICU, in all participants, measures were collected of peripheral muscle strength, balance, walking speed and functional exercise capacity. Recruitment was challenging and ceased prior to achieving the desired sample size. Participants with ALI (n = 22) and critical illness (n = 33) were of similar median age (50 vs. 57 yr, p = 0.09), sex proportion (males %, 45 vs. 58, p = 0.59) and median APACHE II score (21.5 vs. 23.0, p = 0.74). Compared with the participants with critical illness, those with ALI had lower hand grip (mean ± SD, 18 ± 9 vs. 13 ± 8 kg, p = 0.018) and shoulder flexion strength (10 ± 4 vs. 7 ± 3 kg, p = 0.047), slower 10-meter walk speed (median [IQR], 1.03 [0.78 to 1.14] vs. 0.78 [0.67 to 0.94] m/s, p = 0.039) and shorter 6-minute walk distance (265 [71 to 328] vs. 165 [53 to 220] m, p = 0.037). The Berg balance scores were similar in both groups. Compared with survivors of a critical illness that is not ALI, those with ALI are likely to have greater physical impairment when measured shortly after discharge to the ward.

Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib, prevents acute lung injury associated cognitive deficits potentially through suppression of inflammatory response

Acute lung injury (ALI) has been reported to be associated with high mortality rate. Moreover, ALI survivors, frequently present chronic cognitive deterioration. We have previously shown that ‘two hit’ (hydrochloric acid + lipopolysaccharide) induced ALI resulted in cognitive dysfunction through the induction of systemic inflammation. The present study was designed to explore the potential anti-inflammatory effects of olaparib (Poly ADP-ribose polymerase-1 inhibitor), on ALI mediated cognitive impairment. Olaparib was administered at dose of 5 mg/kg body weight (i.p.) 30 min before each hit. Data show that olaparib pre-treatment markedly reduced the neutrophil infiltration, alveolar capillary damage, inflammatory cytokines level (TNF-α/IL-1β/IL-6) and oxidative stress in the lungs at 24 h after ALI induction. Also, olaparib pre-treatment ameliorated the ALI associated cognitive impairment as assessed by Morris water maze test on weekly basis for 2 consecutive weeks. Further, restoration of cognitive function was associated with normalization of serum levels of TNF-α/IL-1β and improved the blood brain barrier (BBB) function, as reflected by data on expression of occludin/claudin-5 and extravasation of Evans-blue/FITC dextran in hippocampus at 1 week post injury. Finally, increased mRNA expression of VCAM-1, TNF-α and IL-1β and NF-κB activation in hippocampus indicate induction of neuro-inflammation, which was downregulated upon olaparib administration. Further, olaparib treatment 1 week after ALI induction blunted the systemic inflammation which was associated with improved BBB and cognitive function. Altogether, our results showed that olaparib protects against ALI and associated cognitive deficits in mice, and thus may offer a new treatment avenue in the area.

Abnormal Exercise Responses in Survivors of Acute Lung Injury During Cardiopulmonary Exercise Testing: AN OBSERVATIONAL STUDY.

This study compared exercise responses in individuals who had recently survived an admission to the intensive care unit for acute lung injury (ALI) with healthy controls. Ten patients with ALI were recruited at 2 Australian hospitals. Six weeks after hospital discharge, participants completed lung function measures and a laboratory-based cardiopulmonary exercise test. Identical measures were collected in 21 healthy participants of similar age and gender distribution. Compared with the healthy participants, the ALI participants were similar in age (51 ± 14 vs 50 ± 16 yr), with a lower peak oxygen uptake ((Equation is included in full-text article.)O2) (median [interquartile range], 31.80 [26.60-41.73] vs 17.80 [14.85-20.85] mL/kg/min; P < .01) and higher ventilatory equivalent for carbon dioxide ((Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2) at anaerobic threshold (mean ± SD, 25.7 ± 2.5 vs 35.2 ± 4.1; P < .01). Analysis of individual ALI participant responses showed that 8 participants had a decreased peak (Equation is included in full-text article.)O2 and anaerobic threshold. All ALI participants were limited by leg fatigue. Abnormalities of pulmonary gas exchange were present in 7 participants. Evidence of cardiac ischemia was present in 2 participants. Compared with healthy controls, ALI participants had reduced exercise capacity, mainly due to profound deconditioning. Exercise training to optimize aerobic capacity would appear to be a rehabilitation priority in this population.

Two hit induced acute lung injury impairs cognitive function in mice: A potential model to study cross talk between lung and brain

Acute lung injury (ALI), a pulmonary inflammatory disorder, is associated with high morbidity and mortality rates. Interestingly, ALI survivors have been reported for some neurocognitive deterioration at/after discharge. However, the molecular factors behind such extra pulmonary manifestation are not clearly known. The present work was designed to investigate lung-brain cross talk in experimental mice for deciphering primary molecular factors that may be involved in ALI-mediated cognitive impairment. ALI was induced in Balb/c mice by intra-tracheal administration of either 0.1 N HCl (2 ml/kg) or LPS (1 mg/kg) as single hits or both agents were administered successively to mimic the ‘two hit’ model. Interestingly two hit-mediated ALI resulted in exaggerated inflammatory response as reflected by increased pulmonary neutrophils and inflammatory factors (TNF-α/IL-1β/IL-6). Additionally, two hits resulted in delayed resolution of lung inflammation and was coupled with persistent decline in memory, as assessed by Morris water maze test. Further, two hits elevate serum levels of TNF-α/IL-1β which was associated with compromised blood brain barrier (BBB), as evident by decreased expression of occludin/claudin-5 and consequent Evans-blue extravasation in hippocampus 1 week post injury. Finally, dexamethasone protects against the two hit mediated cognitive impairment by lowering the pro-inflammatory factors (TNF-α/IL-1β) both in lungs and blood. Overall, we report for the first time that ‘two hit’ mediated ALI cause persistent cognitive impairment in mice partly via up-regulating systemic expression of TNF-α/IL-1β that may disrupt BBB and hence the model may be a useful tool to examine the lung-brain cross-talk at the molecular level for exploring newer therapeutics.

Muscle function recovery after acute lung injury is impaired in aged mice, linked in part, to metabolic alterations attributed to MuRF1 by quantitative targeted metabolomics analysis of acyl‐carnitines

Most survivors of acute lung injury suffer from substantial physical complications months after the initial lung injury resolves, and persistent muscle weakness is a very common sequelae of lung injury. Using a mouse model of LPS‐induced lung injury [acute lung injury (ALI) mice], we found that old (20 month) ALI mice failed to recover skeletal muscle function 10 days after injury compared to young (6 month) ALI control mice. Non‐targeted GC‐MS analysis of old ALI gastrocnemius muscle vs. vehicle treated controls identified 18 significantly different metabolites, including the long chain fatty acid linoleic acid (1.75 fold increased), indicative of altered linoleic acid metabolism. Our laboratory recently identified that muscle ring finger protein 1 (MuRF1) inhibits fatty acid oxidation in vivo via mono‐ubiquitination of peroxisome proliferator‐activated receptor alpha. Moreover, we've identified that MuRF1−/− mice are resistant to LPS‐induced muscle atrophy. Western analysis of old and young ALI muscles for MuRF1 found significantly greater expression of MuRF1 3 days following lung injury in old ALI mice, leading us to hypothesize that old ALI muscles had inhibited fatty acid oxidation. We next performed targeted metabolomics analysis of fatty acid intermediates (acyl‐carnitines) and amino acids of the affected muscles. At day 10, we identified 13 significantly altered acyl carnitines (by t‐test, p&lt;0.05) compared to vehicle treated controls (0.27–1.14 fold). We also identified that total long chain acyl‐carnitines were almost decreased by half, paralleling the acyl‐carnitine profile recently published in MuRF1−/− hearts. Together, these studies demonstrate for the first time age‐associated susceptibility of ALI‐induced muscle wasting and characterize the metabolic alterations in fatty acid metabolism, suggesting MuRF1's role in regulating fatty acid metabolism, which may contribute to impaired skeletal muscle functional recovery.Support or Funding InformationThis work was supported by the National Institutes of Health (R01HL104129 to M.W.), the Leducq Foundation Transatlantic Networks of Excellence (to M.W.), the Claude D. Pepper Older Americans Independence Center (P30AG21332 to D.C.F and O.D.), and the American Thoracic Society Foundation (D.C.F.).

Psychometric evaluation of the Hospital Anxiety and Depression Scale 3 months after acute lung injury

PurposeTo conduct a psychometric evaluation of the Hospital Anxiety and Depression Scale (HADS) and to evaluate associations of 2 measures of psychological distress with the HADS Anxiety (HADS-A) and HADS Depression (HADS-D) subscales in acute lung injury (ALI) survivors. Materials and MethodsWe used 3-month post-ALI follow-up data from 151 participants in a multisite prospective cohort study to evaluate the internal consistency and structure of the HADS subscales and items, respectively. We used Spearman ρ correlations and other statistics to relate the 3-level version of the EuroQol-5D (EQ-5D-3L) anxiety/depression item and Medical Outcomes Study Short Form-36 (SF-36) “mental health”–related domains to the HADS subscales. ResultsInternal consistency was good for each of the HADS subscales (α ≥ .70). Exploratory factor analysis revealed a 2-factor structure (anxiety and depression). The EQ-5D-3L item and the SF-36 mental health–related domain scores were associated with HADS-A (ρ = 0.54 and −0.48 to −0.70, respectively) and HADS-D (ρ = 0.41 and −0.48 to −0.52, respectively) scores (all P < .01). The relationship between the SF-36 mental health domain score and the HADS-A subscale score was particularly strong (ρ = −0.70, P < .01). ConclusionsWhen evaluated in ALI survivors, the HADS has good internal consistency and a 2-factor structure. The HADS subscales were substantially correlated with the EQ-5D-3L anxiety/depression item and SF-36 mental health–related domain scores, suggesting convergent validity for these measures of psychological distress in ALI survivors.

Health care resource use and costs of two-year survivors of acute lung injury. An observational cohort study.

Survivors of acute lung injury (ALI) require ongoing health care resources after hospital discharge. The extent of such resource use, and associated costs, are not fully understood. For patients surviving at least 2 years after ALI, we evaluated cumulative 2-year inpatient admissions and related costs, and the association of patient- and intensive care unit-related exposures with these costs. Multisite observational cohort study in 13 intensive care units at four academic teaching hospitals evaluating 138 two-year survivors of ALI. Two-year inpatient health care use data (i.e., admissions to hospitals, and skilled nursing and rehabilitation facilities) were collected for patients surviving at least 2 years, via (1) one-time retrospective structured interview with patient and/or proxy, (2) systematic medical record review for nonfederal study site hospitals, and (3) inpatient medical record review for non-study site hospitals, as needed for clarifying patient/proxy reports. Costs are reported in 2013 U.S. dollars. A total of 138 of 142 (97%) 2-year survivors completed the interview, with 111 (80%) reporting at least one inpatient admission during follow-up, for median (interquartile range [IQR]) estimated costs of $35,259 ($10,565-$81,166). Hospital readmissions accounted for 76% of costs. Among 12 patient- and intensive care unit-related exposures evaluated, baseline comorbidity and intensive care unit length of stay were associated with increased odds of incurring any follow-up inpatient costs. Having Medicare or Medicaid (vs. private insurance) was associated with median estimated costs that were 85% higher (relative median, 1.85; 95% confidence interval, 1.01-3.45; P=0.045). In this multisite study of 138 two-year survivors of ALI, 80% had one or more inpatient admission, representing a median (IQR) estimated cost $35,259 ($10,565-$81,166) per patient and $6,598,766 for the entire cohort. Hospital readmissions represented 76% of total inpatient costs, and having Medicare or Medicaid before ALI was associated with increased costs. With the aging population and increasing comorbidity, these findings have important health policy implications for the care of critically ill patients.

Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study.

To evaluate the cooccurrence, and predictors of remission, of general anxiety, depression, and posttraumatic stress disorder symptoms during 2-year follow-up in survivors of acute lung injury treated in an ICU. Prospective cohort study, with follow-up at 3, 6, 12, and 24 months post-acute lung injury. Thirteen medical and surgical ICUs in four hospitals. Survivors among 520 patients with acute lung injury. The outcomes of interest were measured using the Hospital Anxiety and Depression Scale anxiety and depression subscales (scores ≥ 8 indicating substantial symptoms) and the Impact of Event Scale-Revised (scores ≥ 1.6 indicating substantial posttraumatic stress disorder symptoms). Of the 520 enrolled patients, 274 died before 3-month follow-up; 186 of 196 consenting survivors (95%) completed at least one Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised assessment during 2-year follow-up, and most completed multiple assessments. Across follow-up time points, the prevalence of suprathreshold general anxiety, depression, and posttraumatic stress disorder symptoms ranged from 38% to 44%, 26% to 33%, and 22% to 24%, respectively; more than half of the patients had suprathreshold symptoms in at least one domain during 2-year follow-up. The majority of survivors (59%) with any suprathreshold symptoms were above threshold for two or more types of symptoms (i.e., general anxiety, depression, and/or posttraumatic stress disorder). In fact, the most common pattern involved simultaneous general anxiety, depression, and posttraumatic stress disorder symptoms. Most patients with general anxiety, depression, or posttraumatic stress disorder symptoms during 2-year follow-up had suprathreshold symptoms at 24-month (last) follow-up. Higher Short-Form-36 physical functioning domain scores at the prior visit were associated with a greater likelihood of remission from general anxiety and posttraumatic stress disorder symptoms during follow-up. The majority of acute lung injury survivors had clinically significant general anxiety, depression, or posttraumatic stress disorder symptoms, and these symptoms tended to co-occur across domains. Better physical functioning during recovery predicted subsequent remission of general anxiety and posttraumatic stress disorder symptoms.

Personalized contact strategies and predictors of time to survey completion: analysis of two sequential randomized trials.

BackgroundEffective strategies for contacting and recruiting study participants are critical in conducting clinical research. In this study, we conducted two sequential randomized controlled trials of mail- and telephone-based strategies for contacting and recruiting participants, and evaluated participant-related variables’ association with time to survey completion and survey completion rates. Subjects eligible for this study were survivors of acute lung injury who had been previously enrolled in a 12-month observational follow-up study evaluating their physical, cognitive and mental health outcomes, with their last study visit completed at a median of 34 months previously.MethodsEligible subjects were contacted to complete a new research survey as part of two randomized trials, initially using a randomized mail-based contact strategy, followed by a randomized telephone-based contact strategy for non-responders to the mail strategy. Both strategies focused on using either a personalized versus a generic approach. In addition, 18 potentially relevant subject-related variables (e.g., demographics, last known physical and mental health status) were evaluated for association with time to survey completion.ResultsOf 308 eligible subjects, 67% completed the survey with a median (IQR) of 3 (2, 5) contact attempts required. There was no significant difference in the time to survey completion for either randomized trial of mail- or phone-based contact strategy. Among all subject-related variables, age ≤40 years and minority race were independently associated with a longer time to survey completion.ConclusionWe found that age ≤40 years and minority race were associated with a longer time to survey completion, but personalized versus generic approaches to mail- and telephone-based contact strategies had no significant effect. Repeating both mail and telephone contact attempts was important for increasing survey completion rate.Trial registrationNCT00719446.

Risk Factors for Physical Impairment after Acute Lung Injury in a National, Multicenter Study

Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size. To evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization. A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness-related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status. At 6 and 12 months, respectively, mean (± SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (± 8%) and 93% (± 9%), 6-minute-walk distance (as percent-predicted) was 64% (± 22%) and 67% (± 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (± 36%) and 67% (± 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes. Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors' physical outcomes.

Physical Complications in Acute Lung Injury Survivors

Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life. Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and health-related quality of life and their associations with critical illness and ICU exposures. A multisite prospective study with longitudinal follow-up at 3, 6, 12, and 24 months after acute lung injury. Thirteen ICUs from four academic teaching hospitals. Two hundred twenty-two survivors of acute lung injury. None. At each time point, patients underwent standardized clinical evaluations of extremity, hand grip, and respiratory muscle strength; anthropometrics (height, weight, mid-arm circumference, and triceps skin fold thickness); 6-minute walk distance, and the Medical Outcomes Short-Form 36 health-related quality of life survey. During their hospitalization, survivors also had detailed daily evaluation of critical illness and related treatment variables. Over one third of survivors had objective evidence of muscle weakness at hospital discharge, with most improving within 12 months. This weakness was associated with substantial impairments in physical function and health-related quality of life that persisted at 24 months. The duration of bed rest during critical illness was consistently associated with weakness throughout 24-month follow-up. The cumulative dose of systematic corticosteroids and use of neuromuscular blockers in the ICU were not associated with weakness. Muscle weakness is common after acute lung injury, usually recovering within 12 months. This weakness is associated with substantial impairments in physical function and health-related quality of life that continue beyond 24 months. These results provide valuable prognostic information regarding physical recovery after acute lung injury. Evidence-based methods to reduce the duration of bed rest during critical illness may be important for improving these long-term impairments.

Duration of oral endotracheal intubation is associated with dysphagia symptoms in acute lung injury patients

PurposeThe purpose of this study is to evaluate demographic and clinical factors associated with self-reported dysphagia after oral endotracheal intubation and mechanical ventilation in patients with acute lung injury (ALI). Materials and methodsThis is a prospective cohort study of 132 ALI patients who had received mechanical ventilation via oral endotracheal tube. ResultsThe primary outcome was binary, whether clinically important symptoms of dysphagia at hospital discharge were reported by patients, using the Sydney Swallowing Questionnaire score 200 or more. Of 132 patients, 29% reported clinically important symptoms of dysphagia. Of 18 relevant demographic and clinical variables, only 2 were found to be independently associated with clinically important symptoms of dysphagia in a multivariable logistic regression model: upper gastrointestinal comorbidity (odds ratio, 2.82; 95% confidence interval, 1.09-7.26) and duration of oral endotracheal intubation (odds ratio, 1.79; [95% confidence interval, 1.15-2.79] per day for first 6 days, after which additional days of intubation were not associated with a further increase in the odds of dysphagia). ConclusionsIn ALI survivors, patient-reported, postexubation dysphagia at hospital discharge was significantly associated with upper gastrointestinal comorbidity and a longer duration of oral endotracheal intubation during the first 6 days of intubation.

Posttraumatic Stress Disorder in Survivors of Acute Lung Injury

Survivors of acute lung injury (ALI) and other critical illnesses often experience substantial posttraumatic stress disorder (PTSD) symptoms. However, most questionnaires have not been validated against a PTSD diagnostic reference standard in this patient population. Hence, in the current study of survivors of ALI, we evaluated the Impact of Events Scale-Revised (IES-R), a questionnaire measure of PTSD symptoms, against the Clinician-Administered PTSD Scale (CAPS), the current state-of-the-art PTSD diagnostic reference standard, which also provides a quantitative assessment of PTSD symptoms.We evaluated the IES-R questionnaire vs the CAPS diagnostic interview in 60 of 77 consecutively recruited survivors of ALI from two prospective cohort studies of patients 1 to 5 years after ALI.The IES-R total score (range: 0.0-3.2) and the CAPS total severity score (range: 0-70) were strongly related (Pearson r=0.80, Spearman ρ=0.69). Using CAPS data, eight of the 60 patients (13%) had PTSD at the time of assessment, and an additional eight patients had partial PTSD (total prevalence, 27%). In a receiver operating characteristics curve analysis with CAPS PTSD or partial PTSD as criterion variables, the area under the curve ranged from 95% (95% CI, 88%-100%) to 97% (95% CI, 92%-100%). At an IES-R threshold of 1.6, with the same criterion variables, sensitivities ranged from 80% to 100%, specificities 85% to 91%, positive predictive values 50% to 75%, negative predictive values 93% to 100%, positive likelihood ratios 6.5 to 9.0, negative likelihood ratios 0.0 to 0.2, and efficiencies 87% to 90%.The IES-R appears to be an excellent brief PTSD symptom measure and screening tool in ALI survivors.

One year outcomes in patients with acute lung injury randomised to initial trophic or full enteral feeding: prospective follow-up of EDEN randomised trial

Objective To evaluate the effect of initial low energy permissive underfeeding (“trophic feeding”) versus full energy enteral feeding (“full feeding”) on physical function and secondary outcomes in patients with acute...

Chest CT Features are Associated With Poorer Quality of Life in Acute Lung Injury Survivors*

Despite decreasing mortality rates in acute lung injury, studies of long-term physical function in acute lung injury survivors have consistently reported poorer quality of life persisting years into recovery for reasons that are not completely understood. We sought to determine if pulmonary dysfunction is independently associated with functional impairment among acute lung injury survivors and to determine if high-resolution computed tomography could be used to predict its development. Secondary analysis of data from a randomized controlled trial in acute lung injury. ICUs at three academic medical centers. Patients diagnosed with acute lung injury who had high-resolution computed tomography scans performed at 14 and/or 180 days after diagnosis. None. An objective radiologic scoring system was used to quantify patterns present on chest high-resolution computed tomography obtained at 14 and 180 days in patients with acute lung injury. These scores were correlated in univariable and multivariable analyses with pulmonary function testing and quality of life survey data obtained at 180 days. Eighty-nine patients had evaluable data at day 14, and 47 at 180 days. At 180 days, increased radiologic scores for reticulation were associated with a decreased total lung capacity, forced vital capacity, and diffusing capacity for carbon monoxide (p values all < 0.002). Decrements in quality of life attributable to pulmonary dysfunction were most strongly associated with higher radiologic scores. Additionally, radiologic scores at 14 days independently predicted poorer quality of life at 180 days, accounting for age, severity of illness, pneumonia as the acute lung injury risk factor, and length of time on mechanical ventilation. Among survivors of acute lung injury, increasing chest high-resolution computed tomography involvement correlated with restrictive physiology and poorer health-related quality of life, implicating pulmonary dysfunction as a potential contributor to activity limitation in these patients.

The Adult Respiratory Distress Syndrome Cognitive Outcomes Study: long-term neuropsychological function in survivors of acute lung injury

Expanded abstractCitationMikkelsen ME, Christie JD, Lanken PN, Biester RC, Thompson BT, Bellamy SL, Localio AR, Demissie E, Hopkins RO, Angus DC: The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med 2012, 185:1307-1315.BackgroundCognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking.MethodsObjectiveThe objectives were to determine whether a validated telephone-based neuropsychological test battery is feasible in a multicenter trial and to determine the frequency and risk factors for long-term neuropsychological impairment.DesignA prospective, multicenter cohort study of a subset of survivors from the Fluid and Catheter Treatment Trial (FACTT) was conducted.SettingThe FACTT enrolled patients from 38 North American hospitals between June 2000 and October 2005.SubjectsTo be eligible for the ALI Cognitive Outcomes Study (ACOS), subjects had to be enrolled in the FACTT and the EA-PAC (Economic Assessment of the Pulmonary Artery Catheter) trial. The FACTT enrolled mechanically ventilated adults who met the American-European Consensus Conference criteria for ALI.InterventionIn an adjunct study to the Acute Respiratory Distress Syndrome Clinical Trials Network Fluid and Catheter Treatment Trial, neuropsychological function at 2 and 12 months after hospital discharge was assessed.OutcomesThe primary outcome was the result of a validated telephone battery of standardized neuropsychological tests administered to consenting, English-speaking subjects at 2 and 12 months after hospital discharge.ResultsOf 406 eligible survivors, 261 patients were approached to participate and 213 consented. One hundred twenty-two subjects, including 102 subjects at 12 months, were tested at least once. Memory, verbal fluency, and executive function were impaired in 13% (12 of 92), 16% (15 of 96), and 49% (37 of 76) of long-term survivors, respectively. Long-term cognitive impairment was present in 41 (55%) of the 75 survivors who completed cognitive testing. Depression, post-traumatic stress disorder, and anxiety were present in 36% (37 of 102), 39% (40 of 102), and 62% (63 of 102) of long-term survivors, respectively. Enrollment in a conservative fluid management strategy (P <0.005) was associated with cognitive impairment, and lower partial pressure of arterial oxygen during the trial was associated with cognitive (P <0.02) and psychiatric (P <0.02) impairment.ConclusionsNeuropsychological function can be assessed by telephone in a multicenter trial. Long-term neuropsychological impairment is common in survivors of ALI. Hypoxemia is a risk factor for long-term neuropsychological impairment. A fluid management strategy is a potential risk factor for long-term cognitive impairment; however, given the select population studied and an unclear mechanism, this finding requires confirmation.

Quality of Life Before Intensive Care Using EQ-5D

To compare patients' retrospectively reported baseline quality of life before intensive care hospitalization with population norms and proxy reports. Prospective cohort study. Thirteen ICUs at four teaching hospitals in Baltimore, MD. One hundred forty acute lung injury survivors and their designated proxies. Around the time of hospital discharge, both patients and proxies were asked to retrospectively estimate patients' baseline quality of life before hospital admission using the EQ-5D quality-of-life instrument. Mean patient-rated EQ-5D visual analog scale scores and utility scores were significantly lower than population norms but were significantly higher than proxy ratings. However, the magnitude of difference in average utility scores between patients and either population norms or proxies was not clinically important. For the five individual EQ-5D domains, κ statistics revealed slight to fair agreement between patients and proxies. Bland-Altman plots demonstrated that for both the visual analog scale and utility scores, proxies underestimated scores when patients reported high ratings and overestimated scores for low patient ratings. Patients retrospectively reported worse baseline health status before acute lung injury than population norms and better status than proxy reports; however, the magnitude of these differences in health status may not be clinically important. Proxies had only slight to fair agreement with patients in all five EQ-5D domains, attenuating patients' more extreme ratings toward moderate scores. Caution is required when interpreting proxy retrospective reports of baseline health status for survivors of acute lung injury.

Post-discharge insomnia symptoms are associated with quality of life impairment among survivors of acute lung injury

Sleep disturbance is common during critical illness, yet little is known about its prevalence or role in post-discharge quality of life among high-risk acute lung injury (ALI) patients. In a prospective cohort of 61 mechanically ventilated ALI patients, we examined the association between insomnia symptoms and quality of life six months after discharge. Subjects completed surveys rating quality of life (MOS SF-36), post-traumatic stress disorder (PCL), and depression (PHQ-9). Using an individual item from the PCL, we defined insomnia symptoms as moderate or greater trouble falling or staying asleep in the past month. We performed multivariable linear regression to examine the association between insomnia symptoms and SF-36 physical and mental component summary scores, adjusting for PTSD and depression. Forty subjects (85% of eligible) completed six-month questionnaires; 20 (50%) met criteria for insomnia symptoms. After adjustment for PTSD and depression, insomnia symptoms remained significantly associated with worse physical component summary scores (adjusted mean difference=-8.8; 95% CI: -15.0, -2.5; P<0.01). Post-discharge insomnia symptoms were common and significantly associated with physical quality of life impairment among six-month ALI survivors, even after adjustment for PTSD and depression symptoms. Further studies are needed to validate these results and to characterize sleep disturbance after ALI using sleep-specific metrics.

Long-term neuropsychological impairment is common in acute lung injury survivors

Long-term neuropsychological impairment is common in acute lung injury survivors