Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.     

Family member satisfaction with end-of-life decision making in the ICU

RATIONALE: Families of ICU patients may be at risk for increased psychological morbidity due to end-of-life decision making. The identification of chart-based quality indicators of palliative care that predict family satisfaction with decision making may help to guide interventions to improve decision making and family outcomes. OBJECTIVE: To determine patient and family characteristics and chart the documentation of processes of care that are associated with increased family satisfaction with end-of-life decision making for ICU patients. METHODS: We conducted a cohort study of ICU patients dying in 10 medical centers in the Seattle-Tacoma area. Measurement: Outcomes from family surveys included summary scores for family satisfaction with decision making and a single-item score that indicated feeling supported during decision making. Predictor variables were obtained from surveys and chart abstraction. Main results: The survey response rate was 41% (442 of 1,074 families responded). Analyses were conducted of 356 families with questionnaire and chart abstraction data. Family satisfaction with decision making was associated with the withdrawal of life support, and chart documentation of physician recommendations to withdraw life support, discussions of patients' wishes, and discussions of families' spiritual needs. Feeling supported during decision making was associated with the withdrawal of life support, spiritual care involvement, and chart documentation of physician recommendations to withdraw life support, expressions of families' wishes to withdraw life support, and discussions of families' spiritual needs. CONCLUSIONS: Increased family satisfaction with decision making is associated with withdrawing life support and the documentation of palliative care indicators including the following: physician recommendations to withdraw life support; expressions of patients' wishes; and discussions of families' spiritual needs. These findings provide direction for future studies to investigate approaches to improving family satisfaction in end-of-life decision making. In addition, because there were few nonwhites in this study, these results may not be generalizable to more diverse populations. Future studies should target diverse populations in order to test whether similar factors are similarly important for end-of-life decision making.     

Prognosis of lung cancer patients with life-threatening complications

BACKGROUND: The management of patients with lung cancer has improved recently, and many of them will require admission to the ICU. The aims of this study were to determine hospital mortality and to identify risk factors for death in a large cohort of critically ill patients. METHODS: Cohort study in two ICUs specialized in the management of patients with cancer, in France and Brazil. RESULTS: Of the 143 patients (mean age, 61.6 +/- 9.9 years [+/- SD]), 25 patients (17%) had small cell lung cancer and 118 patients (83%) had non-small cell lung cancer. The main reasons for ICU admission were sepsis (44%) and acute respiratory failure (31%). Mechanical ventilation (MV) was used in 100 patients (70%), including 38 patients in whom lung cancer was considered a reason for MV. Hospital mortality was 59% overall and 69% in patients receiving MV. By multivariate logistic regression, airway infiltration or obstruction by cancer, number of organ failures, cancer recurrence or progression, and severity of comorbidities were associated with increased mortality. CONCLUSIONS: The improved survival previously reported in patients with cancer admitted to the ICU seems to extend to patients with lung cancer, including those who need MV. Mortality increased with the number of organ failures, severity of comorbidities, and presence of respiratory failure due to cancer progression. The type of the cancer per se was not associated with mortality and, therefore, should not be factored into ICU triage decisions.     

Targeting growth factors in lung cancer

Lung cancer causes more deaths than any other malignancy in the developed world. Advances in surgical techniques and chemotherapy/radiotherapy regimes have produced only minimal improvements in long-term survival. New therapeutic interventions are urgently required. Research has indicated that growth factor signaling may be an important novel target in lung cancer therapy. Preclinical studies have demonstrated the role of extracellular growth factors in lung cancer cell proliferation, metastasis, and resistance to cytotoxic therapy, and have elucidated the key molecular components of growth factor-signaling cascades. This has enabled the development of selective growth factor inhibitors, which have been evaluated in clinical trials and are now an accepted component of advanced lung cancer treatment. Further research is underway to improve the efficacy of this growth factor-targeted therapy. This article will outline the important aspects of this translational research indicating the growth factor-signaling pathways identified in lung cancer, clinical trials of anti-growth factor therapy, and potential future research directions.     

Panton-Valentine Leukocidin-positive methicillin-resistant Staphylococcus aureus lung infection in patients with cystic fibrosis

BACKGROUND: Panton-Valentine Leukocidin-expressing (PVL+) methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen worldwide causing fatal necrotizing pneumonias in otherwise healthy individuals but has not been described in patients with cystic fibrosis (CF). Following two cases of patients with CF admitted with lung abscesses in association with PVL+ MRSA, we examined the incidence and the clinical characteristics of MRSA acquisition in our CF patient population. METHODS: Newly acquired MRSA isolates from patients with CF followed up at St. Louis Children's Hospital were analyzed for the presence of Panton-Valentine leukocidin coding region, clindamycin susceptibility, staphylococcal cassette chromosome (SCC) mec type, and multilocus sequence type. Medical records and pulmonary function studies at the time of MRSA isolation were reviewed. RESULTS: MRSA isolates from 40 CF patients were available for analysis. Six children (15%) had PVL+ MRSA infection. All PVL+ organisms were clindamycin susceptible. Patients who acquired a PVL+ organism were more likely to have a focal pulmonary infiltrate on chest radiograph, including cavitary lung lesions in two patients (p = 0.04), a markedly greater decline in FEV1 at the time of MRSA detection (p = 0.01), and a significantly higher WBC count (p = 0.04) and absolute neutrophil count (p = 0.04). These patients were more likely to be admitted for IV antibiotic therapy for respiratory illnesses (p < 0.01). CONCLUSIONS: We describe the emergence of PVL+ MRSA in our CF population in association with development of invasive lung infections including lung abscesses. Early identification and treatment of CF patients with newly acquired PVL+ MRSA may be crucial.     

Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

BACKGROUND: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity. OBJECTIVE: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay. RESULTS: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients. CONCLUSIONS: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.     

Patient-focused sedation and analgesia in the ICU

Patient-focused sedation and analgesia in the ICU encompasses a strategy of comprehensive structured management that matches initial evaluation, monitoring, medication selection, and the use of protocols with patient characteristics and needs. This is best accomplished through interdisciplinary management by physicians, nurses, and pharmacists. An early consideration is that of the potential predisposing and precipitating factors, as well as prior sedative or analgesic use, factors that may influence pharmacologic and supportive therapy. Frequent monitoring with validated tools improves communication among clinicians and plays an important role in detecting and treating pain and agitation while avoiding excessive or prolonged sedation. Patient-focused management encompasses selecting medications best suited to patient characteristics, including the presence of organ dysfunction that may influence drug metabolism or excessive risk for side effects. The use of protocols to optimize drug therapy has emerged as a key component of management, resulting in reductions in the duration of sedation, mechanical ventilation, and ICU length of stay demonstrated with strategies to titrate medications to specific targets, daily interruption of sedation, intermittent rather than continuous therapy, and analgesia-based therapy. While much attention is paid to the initiation and maintenance of therapy, greater emphasis must be placed on careful de-escalation of therapy in order to avoid analgesic or sedative withdrawal. Finally, more work is needed to explore the relationship of critical illness and sedation management with long-term psychological outcomes.     

Timeliness of care in veterans with non-small cell lung cancer

BACKGROUND: Timeliness is an important dimension of quality of care for patients with lung cancer. METHODS: We reviewed the records of consecutive patients in whom non-small cell lung cancer (NSCLC) had been diagnosed between January 1, 2002, and December 31, 2003, at the Veterans Affairs Palo Alto Health Care System. We used multivariable statistical methods to identify independent predictors of timely care and examined the effect of timeliness on survival. RESULTS: We identified 129 veterans with NSCLC (mean age, 67 years; 98% men; 83% white), most of whom had adenocarcinoma (51%) or squamous cell carcinoma (30%). A minority of patients (18%) presented with a solitary pulmonary nodule (SPN). The median time from the initial suspicion of cancer to treatment was 84 days (interquartile range, 38 to 153 days). Independent predictors of treatment within 84 days included hospitalization within 7 days (odds ratio [OR], 8.2; 95% confidence interval [CI], 2.9 to 23), tumor size of > 3.0 cm (OR, 4.8; 95% CI, 1.8 to 12.4), the presence of additional chest radiographic abnormalities (OR, 3.0; 95% CI, 1.1 to 8.5), and the presence of one or more symptoms suggesting metastasis (OR, 2.6; 95% CI, 1.1 to 6.2). More timely care was not associated with better survival time (adjusted hazard ratio, 1.6; 95% CI, 1.3 to 1.9). However, in patients with SPNs, there was a trend toward better survival time when the time to treatment was < 84 days. CONCLUSIONS: The time to treatment for patients with NSCLC was often longer than recommended. Patients with larger tumors, symptoms, and other chest radiographic abnormalities receive more timely care. In patients with malignant SPNs, survival may be better when treatment is initiated promptly.     

The effect of body mass index on patient outcomes in a medical ICU

STUDY OBJECTIVES: To examine the effect of patient body mass index (BMI) on outcome in intensive care. DESIGN: In a prospective study, the patients were classified into groups based on the calculated BMI, as follows: BMI < 19.0 (n = 350), > or = 19.0 and < 25.0 (n = 663), > or = 25.0 and < 29.9 (n = 585), > or = 30.0 and < 40.0 (n = 396), and > or = 40.0 (n = 154). Groups were compared by age, APACHE (acute physiology and chronic health evaluation) II score, mortality, ICU length of stay (LOS), hospital LOS, number receiving ventilation, and ventilator-days. Adverse events including nosocomial pneumonia, ventilator-days per patient, failed extubations, and line-related complications were recorded. SETTING: The study was conducted in a 9-bed medical ICU of a 650-bed tertiary care hospital. MEASUREMENTS: Height and weight were prospectively recorded for the first ICU admission during a hospital stay. RESULTS: Between January 1, 1997, and August 1, 2001, 2,148 of 2,806 patients admitted to the ICU had height and weight recorded. There were no differences in APACHE II score, mortality, ICU LOS, hospital LOS, number receiving ventilation, ventilator-days, average total cost, or average variable cost among the five groups. However, the severely obese patients were more frequently female and younger than those who were overweight and obese (p < 0.001). Adverse events were infrequent, but there were no differences between the obese/very obese compared with others. CONCLUSION: BMI has minimal effects on ICU outcome after patients are admitted to a critical care unit.     

Health-related quality of life trajectories among adults with tuberculosis: differences between latent and active infection

BACKGROUND: Tuberculosis (TB) remains a public health threat with significant annual impacts on morbidity and mortality. However, few studies have examined the impact of active and latent TB infection (LTBI) on health-related quality of life (HRQL). METHODS: Patients with recently diagnosed active TB or LTBI patients were administered the Short Form-36 (SF-36) and the Beck depression inventory (DI) at baseline, 3 months, and 6 months. Mixed-effect linear regression was used to compare the trajectory of HRQL over time in the two patient groups after adjusting for potential confounders. Ordinal logistic regression was used to determine the relationship between changes in HRQL of at least the minimal important difference. RESULTS: One hundred four active TB and 102 LTBI patients participated. At baseline, participants with active TB had significantly lower SF-36 mean domain and component scores (4 to 12 points lower, p < 0.03) and higher mean Beck DI scores (4 points higher, p < 0.0001) when compared to LBTI participants. In the responder analysis, those with active TB were associated with reporting improved scores at 6 months of at least the minimal important difference in vitality (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.6), role physical (OR, 3.1; 95% CI, 1.4 to 6.5), mental component score (OR, 3.2; 95% CI, 1.5 to 6.9), social functioning (OR, 11.1; 95% CI, 3.8 to 33), and role emotional (OR, 2.7; 95% CI, 1.2 to 6.0). CONCLUSIONS: Active TB patients had large improvements in most HRQL domains by 6 months. However, when compared to LTBI participants and US norms, HRQL was still low at completion of therapy.     

Outcome of patients with small-vessel vasculitis admitted to a medical ICU

PURPOSES: This study aims to describe the clinical course and prognostic factors of patients with small-vessel vasculitis admitted to a medical ICU. METHODS: We reviewed the clinical records of 38 patients with small-vessel vasculitis admitted consecutively to the ICU between January 1997 and May 2004. The APACHE (acute physiology and chronic health evaluation) III prognostic system was used to determine the severity of illness on the first ICU day; the sequential organ failure assessment (SOFA) score was used to measure organ dysfunction, and the Birmingham vasculitis activity score for Wegener granulomatosis (BVAS/WG) was used to assess vasculitis activity. Outcome measures were the 28-day mortality and ICU length of stay. RESULTS: Nineteen patients (50%) had Wegener granulomatosis, 16 patients (42%) had microscopic polyangiitis, 2 patients had CNS vasculitis, and 1 patient had Churg-Strauss syndrome. Reasons for ICU admission included alveolar hemorrhage in 14 patients (37%), sepsis in 5 patients (13%), seizures in 3 patients (8%), and pneumonia in 2 patients (5%). The median ICU length of stay was 4.0 days (interquartile range, 2.0 to 6.0 days). The APACHE III score was lower in survivors than nonsurvivors (p = 0.010). The predicted hospital mortality was 54% for nonsurvivors and 21% for survivors (p = 0.0038). The mean SOFA score was 11.6 (SD, 2.6) in nonsurvivors, compared to 6.9 (SD, 2.4) in survivors (p = 0.0004). Mean BVAS/WG scores were 8.6 (SD, 3.6) in nonsurvivors and 4.7 (SD, 4.6) in survivors (p = 0.0889). Twenty-six percent of the patients received invasive mechanical ventilation, and 33% underwent dialysis. The 28-day and 1-year mortality rates were 11% and 29%, respectively. CONCLUSIONS: The mortality of patients with small-vessel vasculitis admitted to the ICU is lower than predicted, and alveolar hemorrhage is the most common reason for ICU admission.     

Racial differences in cancer risk among relatives of patients with early onset lung cancer

BACKGROUND: Relatives of patients with early onset lung cancer are at increased risk for lung cancer, and this risk varies by race. This study evaluates whether first-degree relatives of patients with early onset lung cancer are at increased risk for cancer at sites other than lung. METHODS: Family histories were ascertained from 673 lung cancer patients < 50 years of age identified from the Metropolitan Detroit Surveillance, Epidemiology and End Results program, and 773 age-, race-, and sex-matched control subjects were obtained via random-digit dialing. Data were collected for 3,556 case relatives (mothers, fathers, and siblings) and 3,943 control relatives, and unconditional logistic regression models using generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among case relatives, African Americans were 2.44-fold more likely to have head and neck cancers and 1.86-fold more likely to have any tobacco-related cancer compared to white case relatives (95% CI, 1.04 to 5.69% and 95% CI, 1.25 to 2.76, respectively). African-American case relatives were at increased risk for head and neck cancers (OR, 13.42; 95% CI, 1.65 to 109.01), all tobacco-related cancers (OR, 3.77; 95% CI, 2.16 to 6.55), tobacco-related cancers other than lung (OR, 4.10; 95% CI, 1.56 to 10.79), and cancer at any site (OR, 1.45, 95% CI, 1.04 to 2.02) compared to African-American control relatives. CONCLUSIONS: These results can be used to counsel family members of patients with early onset lung cancer, and suggest target populations for preventive strategies, including smoking cessation and appropriate screening.     

Warfarin and antiplatelet combination use among commercially insured patients enrolled in an anticoagulation management service

BACKGROUND: Although warfarin and antiplatelet medications have documented efficacy for prevention of primary and secondary cardiovascular events, the appropriateness of warfarin and antiplatelet combination therapy is not well described in national consensus guidelines. METHODS AND RESULTS: Cross-sectional data from 4,557 Kaiser Permanente Colorado members > or = 18 years old who were receiving warfarin anticoagulation therapy were used to quantify the prevalence of warfarin and antiplatelet agent (ie, aspirin, clopidogrel, dipyridamole, and/or dipyridamole/aspirin) combination therapy as of September 30, 2005, and to identify characteristics of patients receiving combination therapy. The prevalence of warfarin and any antiplatelet combination therapy was 385/1,000 (95% confidence interval [CI], 371/1,000 to 399/1,000). The majority of combination therapy was warfarin and aspirin (prevalence, 378/1,000) with a daily dose of aspirin, 81 mg, being the most reported dose (prevalence, 328/1,000). Patients receiving combination therapy were more likely to be male (63.6% vs 46.4%; adjusted odds ratio, 1.5; 95% CI, 1.3 to 1.7) and have a comorbidity of heart failure (29.0% vs 15.6%; adjusted odds ratio, 1.2; 95% CI, 1.1 to 1.5), coronary artery disease (62.4% vs 17.5%; adjusted odds ratio, 7.6; 95% CI, 6.5 to 8.8), and/or stroke/transient ischemic attack (5.2% vs 1.6%; adjusted odds ratio, 3.5; 95% CI, 2.3 to 5.3). CONCLUSION: Nearly 4 of 10 patients receiving warfarin management care were receiving warfarin and antiplatelet combination therapy. The findings suggest that this practice is widespread, especially among patients with established cardiovascular disease, and involves a substantially higher number of patients than previously reported. The clinical outcomes associated with this practice require further investigation.     

Acute febrile respiratory illness in the ICU: reducing disease transmission

Acute febrile respiratory illness (FRI) leading to respiratory failure is a common reason for admission to the ICU. Viral pneumonia constitutes a portion of these cases, and often the viral etiology goes undiagnosed. Emerging viral infectious diseases such as severe acute respiratory syndrome and avian influenza present with acute FRIs progressing to respiratory failure and ARDS. Therefore, early recognition of a viral cause of acute FRI leading to ARDS becomes important for protection of health-care workers (HCWs), lessening spread to other patients, and notification of public health officials. These patients often have longer courses of viral shedding and undergo higher-risk procedures that may potentially generate aerosols, such as intubation, bronchoscopy, bag-valve mask ventilation, noninvasive positive pressure ventilation, and medication nebulization, further illustrating the importance of early detection and isolation. A small number of viral agents lead to acute FRI, respiratory failure, and ARDS: seasonal influenza, avian influenza, coronavirus associated with severe ARDS, respiratory syncytial virus, adenovirus, varicella, human metapneumovirus, and hantavirus. A systematic approach to early isolation, testing for these agents, and public health involvement becomes important in dealing with acute FRI. Ultimately, this approach will lead to improved HCW protection, reduction of transmission to other patients, and prevention of transmission in the community.