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1 Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan
Correspondence and requests for reprints should be addressed to Kevin R. Flaherty, M.D., M.S., Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, 1500 E Medical Center Drive, 3916 Taubman Center, Ann Arbor, MI 48109. E-mail: flaherty{at}umich.edu
PEDIATRIC PULMONARY AND CRITICAL CARE
Adrienne Randolph
Children's Hospital Boston
Boston, Massachusetts
Anemia, Blood Loss, and Blood Transfusions in Critically Ill Children
Blood transfusions are associated with potential risks such as volume overload, transmission of disease agents, immunosuppression, transfusion reactions, etc. Bateman and colleagues sought to understand the development of anemia, blood loss, and red cell transfusions in the pediatric intensive care unit (PICU) (1). Prospective data were collected from 977 children (age < 18 yr) who stayed at least 48 hours in 30 PICUs. Anemia was common. Upon admission, 33% of children had anemia; an additional 48% became anemic during their PICU stay. Children presenting with anemia were sicker (PRISM III 5.3 ± 5.8) than those who developed anemia during the admission (PRISM III 3.8 ± 5.1), who were likewise sicker than children never developing anemia (PRISM III 3.3 ± 4.5, P < 0.0001). There was no difference in average blood loss between these groups. The main source of blood loss was phlebotomy, which accounted for 73%. Overall, 475 (49%) of children received at least one transfusion and an additional 6% received transfusion after PICU discharge. Children that received a transfusion were younger (4.5 versus 6.6 yr, P < 0.001), more likely to be anemic (44 versus 22%, P < 0.001), and had higher baseline PRISM III scores. The reason most often cited for transfusion was low hemoglobin; however, pre-transfusion hemoglobin values varied (mean 9.7 ± 2.7 g/dl). Risk-adjusted analysis showed an association between transfusion and longer duration of mechanical ventilation and ICU stay, and higher mortality and nosocomial infections. Thus, anemia and transfusions are common in the PICU and associated with worse outcomes. As blood draws were the main source of blood loss, strategies to minimize these may help decrease the rate of transfusions.
Impact of Tight Glucose Control in the Critically Ill Children
The impact of tight glucose control in pediatric intensive care unit patients is unknown. The outcomes of studies in adult ICU patients have varied in result, perhaps due to patient populations and/or study design (2–4). Vlasselaers and colleagues reported the results of a randomized trial of tight glucose control in critically ill infants (age < 1 yr, n = 317) and children (n = 383) (5). Targets for tight glucose control were 51 to 71 mg/dl for infants and 70 to 101 mg/dl for children, compared with the prevention of hyperglycemia > 214 mg/dl in control subjects. The majority (75%) of the population was made up of cardiac surgery patients. Intensive versus conventional therapy was associated with lower mortality (2.6% versus 5.7%, P = 0.038). The intensive group also had a 24% higher rate of hypoglycemia (< 40 mg/dl). The cohort is being followed to determine if consequences of the hypoglycemia develop.
Outcome Prediction in Pediatric Septic Shock
Sepsis is an important cause of mortality for children, even though most will survive. Being able to identify those children at higher risk of morality could facilitate the study of interventions by targeting clinical trials to the group of subjects most likely to benefit. This could increase the efficiency of the evaluation of novel interventions by decreasing the sample size needed and thus allow for shorter accrual times and more rapid study completion. Recently, Wong and colleagues evaluated the potential of interleukin 8 (IL-8) obtained within 24 hours of admission to predict 28-day mortality (6). A derivation cohort of 40 subjects identified an IL-8 level of 220 pg/ml as a possible surrogate for subsequent survival. This level was tested in two separate validation cohorts. Although children with an IL-8 level > 220 pg/ml were more likely to die (36/179, 20% versus 8/154, 5%; P < 0.001), the fact that most children survived resulted in a low positive predictive value (20%; 95% confidence interval [CI], 15–27%). To the contrary, having an IL-8 level less than 200 pg/ml was a good predictor of survival, with a negative predictive value of 95% (95% CI, 90–98%). Thus, a serum IL-8 level of less than 220 pg/ml obtained during the first 24 hours of admission may help to exclude a group of subjects with a low risk of morality from clinical trials using mortality as an endpoint. Prospective validation of these findings is needed.
Immune Response in Fatal Respiratory Syncytial Virus and Influenza Virus Infections in Infants
Respiratory syncytial virus (RSV) and influenza (INF) are common causes of severe lower respiratory tract infections in infants. It has been hypothesized that more severe cases or those resulting in death are due to an overactive inflammatory immune response leading to ARDS. Welliver and colleagues compared cytokines and chemokines from secretions of infants surviving RSV and INF infections to determine which mediators were associated with more severe disease (7). They also analyzed lung tissue from fatal cases. Overall lymphocyte derived cytokine levels were low. Levels in RSV survivors were lower than those in INF survivors. Examination of post-mortem lung tissue showed extensive presence of viral antigen and almost complete absence of CD-8–positive lymphocytes and natural killer cells. Markers of apoptosis were prevalent. These authors concluded that infantile bronchiolitis is characterized not by enhanced cytotoxic lymphocyte response but rather by poor viral clearance. Strategies that promote viral clearance could improve outcome.
Post-Traumatic Stress in Children Surviving Critical Illness
Delusional memories are associated with post-traumatic stress in adults after treatment in the intensive care unit (ICU). Colville and colleagues evaluated the presence of post-traumatic stress in children surviving critical illness (8). One hundred two children (aged 7–17 yr) were interviewed 3 months after their discharge from the ICU. Investigators used the ICU memory tool to evaluate specific factual memories as well as an abbreviated Impact of Event Scale to screen for post-traumatic stress disorder. Overall, 64 (63%) of children reported at least one factual experience and 33 (32%) reported delusional memories or disturbing hallucinations. There was an association between longer opiate/benzodiazepine use and delusional memories (odds ratio, 4.98; 95% CI, 1.3–20.0). Children with delusion memories were more likely to have higher post-traumatic stress scores, even when accounting for severity of illness. The presence of factual memories was not associated with post-traumatic stress. This study highlights the high prevalence of delusional memories in children surviving an ICU stay. These delusions are associated with post-traumatic stress and were associated with prolonged opiate/benzodiazepine use. The impact of an approach to minimize opiate/benzodiazepine use on the presence of delusions and post-traumatic stress requires further study.
CYSTIC FIBROSIS
Chris H. Goss
University of Washington
Seattle, Washington
Basic Science Advances in Cystic Fibrosis
Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene lead to the manifestations of cystic fibrosis (CF) in many patients. With defective/deficient CFTR, there is decreased chloride secretion/increased sodium absorption, leading to bronchial obstruction, infection, inflammation, and eventual airway destruction. The CFTR–/– mouse model of CF is limited in that these animals fail to develop the pulmonary disease, hepatic, or pancreatic aspects of CF seen in humans (9, 10). Rogers and colleagues sought to develop a pig model of CF (11). Given the similar anatomy, biochemistry, physiology, size, lifespan, and genetics of pigs and humans, it was plausible that a pig model of CF would more closely resemble the disease seen in humans. Investigators used homologous recombination of fibroblasts of outbred domestic pigs to disrupt the CFTR gene and somatic cell nuclear transfer to generate CFTR+/– pigs. Breading of CFTR+/– males and CFTR+/– females produced 64 piglets in 6 litters, 20 were CFTR–/–. Northern blot and quantitative RT-PCR did not detect normal CFTR transcripts, and immunoprecipitation did not detect normal CFTR protein. In vivo transepithelial voltage across the nasal epithelia was abnormal as seen in human disease. Meconium ileus was present in all piglets compared with approximately 15% of human infants, possibly due to the genetic similarity of the piglets compared with the diversity of human CF. Whether these piglets will progress to develop lung disease is unknown. However, this model shows promise to help further unravel the pathobiology of CF lung disease and may prove useful to test novel drugs that could impact the primary defect in CF.
Translational Science in Cystic Fibrosis
Pulmonary infections are common in patients with CF. Staphylococcus aureus is common early in life, giving way to Pseudomonas aeruginosa in later years. Sputum culture to determine the organism(s) present and their antimicrobial sensitivity patterns is often used to guide antibiotic selection during periods of exacerbation. It is known, however, that patients often respond to treatment with antibiotics that would not be expected to be successful based on predicted susceptibility patterns. Sibley and colleagues used both traditional microbial culture and culture independent approaches (terminal restriction fragment length polymorphism [T-RFLP]) to evaluate the lower airway microbiology in a patient with CF followed longitudinally (12). They focused particular attention to the Streptococcus milleri group (SMG), as these organisms colonize the respiratory tract, can cause serious infection, and are likely to be overlooked by traditional culture techniques. A single patient with chronic P. aeruginosa infection was followed longitudinally through periods of stability and exacerbation. On average, each sputum sample showed 15 ± 5 unique terminal restriction fragments (T-RF). Some T-RFs, such as P. aeruginosa, were consistently present, while others fluctuated. In 39% of exacerbations, the SMG were the dominant microorganism as detected by T-RFLP but not standard culture techniques. Importantly, successful treatment seemed to correlate with therapy targeted to the SMG versus bacteria isolated from routine cultures. Similar results were seen in evaluation of a second patient. Although these data are limited to only two subjects, they highlight the diversity and complexity of the CF lung microbiological environment as well as the potential limitations of standard culture to understand this environment. Further data are needed to explore the role of SMG in the overall CF population as well in various stages of disease severity.
An additional paper evaluated the potential impact of amiloride therapy on the prevention of CF lung disease. Increased Na+ absorption mediated by epithelial Na+ channels (ENaC) is related to the pathobiology of CF lung disease. Unfortunately, amiloride (an ENac blocker) was not efficacious in the treatment of patients with CF with established pulmonary disease (13, 14). Zhou and colleagues used mice that overexpress the β-subunit, resulting in accelerated Na+ transport and CF-like lung disease (15). These mice develop mucus obstruction, epithelial remodeling/thickening, and mucous hypersecretion during the first weeks of life. In this study newborn, 5-day-old, and 4-week-old β-ENaC and wild-type mice were treated with intranasal amiloride versus placebo for 14 days. Amiloride treatment had no effect on the survival of wild-type mice. β-ENaC mice treated early with amiloride had 70% survival compared with 50% survival in placebo-treated animals. Early treatment also resulted in decreased airway obstruction and decreased airway inflammatory markers. Late (4 week) administration of amiloride did not reduce airway obstruction or inflammation. This study mirrors human studies in that late treatment with amiloride did not have a beneficial effect. It also suggests that early treatment with amiloride could prevent the development of CF lung disease. Further data are needed to determine if these animal data will be confirmed in clinical trials of human disease.
Treatment of Cystic Fibrosis Lung Disease
Until the basic defects leading to CF lung disease can be corrected, antimicrobial therapy will continue to be a mainstay in the treatment for patients with CF lung disease. Aztreonam lysine for inhalation (AZLI) is an aerosolized formulation of the monobactam antibiotic aztreonam and lysine (16). McCoy and colleagues evaluated the impact of inhaled aztreonam lysine in patients who frequently used antibiotics for P. aeruginosa (17). This multicenter, randomized, double-blind, placebo-controlled, study assigned subjects to 75 mg AZLI (two or three times daily) or placebo. After randomization, subjects received open-label inhaled tobramycin for 28 days. Patients subsequently started treatment with AZLI or placebo for an additional 28 days and were followed every 14 days until study completion at Day 84. To be eligible patients had to have CF, be at least 6 years old with P. aeruginosa in the sputum or throat swab at screening, and have had three or more inhaled tobramycin courses in the prior year. Pulmonary function required an FEV1 
25% and 
75% predicted and oxygen saturation of at least 90% on room air. Of 363 screened subjects, 211 completed the inhaled tobramycin run-in. The primary outcome measure, time to need of inhaled or intravenous antipsuedomonal antibiotics, was shorter in the AZLI group (92 versus 71 d, P = 0.002). The pooled AZLI groups also showed improved FEV1 (6.3%; 95% CI, 2.5–10.1; P = 0.001), improved CRQ-R respiratory score (5.01 points; 95% CI, 0.8–9.2; P = 0.02), and lower Sputum Log10 P. aeruginosa colony-forming units (0.66; 95% CI, –1.13 to –0.19; P = 0.006). The incidence of treatment-emergent adverse events was generally comparable between groups, and none was statistically significantly different.
Cystic Fibrosis Clinical Epidemiology
The prevalence of Methacillin-resistant S. aureus (MRSA) has increased from 2.1% in 1996 to 18.9% in 2006 (18). Dasenbrook and colleagues evaluated the association of MRSA infection and rate of decline in FEV1 in patients with CF (19). These investigators used the Cystic Fibrosis Foundation patient registry (CFFPR) (20). MRSA status in the CFFPR was recorded every 3 months. To exclude patients with MRSA upon entry into the cohort, the investigators excluded anyone with MRSA within 2 years of entering the cohort, less than two cultures in the first 2 years, or follow up less than 2 years. Multiple linear regression models were created to estimate the effect of MRSA on FEV1 decline. The first model compared patients with CF with persistent MRSA (three or more positive cultures) to those who never had MRSA. A second model used a paired analysis to evaluate a subject's change in rate of FEV1 decline after acquiring MRSA. Covariates were age, sex, infection with MRSA, Burkholderia cepacia complex, P. aeruginosa, baseline FEV1% predicted, CF-related diabetes, and pancreatic enzyme usage. The total cohort included 17,357 patients with CF. The number of patients with transient MRSA infection (n = 1,703, 49%) was similar to that of those who developed persistent infection (n = 1,732, 51%). For patients aged 8 to 21 years, FEV1 declined faster (2.06% predicted/yr versus 1.44% predicted/yr, P = 0.001) if persistent MRSA infection was present. The magnitude of effect was less in patients aged 22 to 45 years (rate difference 0.12% predicted/yr, P = 0.001). Similarly, patients aged 8 to 21 showed a 25% faster rate of decline in FEV1 after acquiring MRSA infection, while no clinically significant association was noted in patients aged 22 to 45 years. Further data are needed to determine if the association of MRSA and faster decline in FEV1 is causal and the potential mechanisms for causality. This study raises additional questions about the potential impact of MRSA eradication and preservation of lung function.
ASTHMA
John V. Fahy
University of California, San Francisco
San Francisco, California
Asthma and Fungal Sensitization
Fungi such as Cladosporium species, Alternaria species, Penicillium species, Candida species, Trichophyton species, and others common in the environment. Although most people are not infected with these fungi many can show evidence of sensitization (21). Denning and colleagues hypothesized that low levels of colonization or direct external exposure are sufficient to induce an allergic response and pulmonary inflammation in patients with severe asthma (22). These investigators recruited subjects with severe asthma (on high-dose inhaled or chronic daily prednisone for at least 6 mo or 4–6 courses of systemic steroids during the prior 12 or 24 mo). Skin testing for aeroallergens was performed; positive patients were eligible if total IgE was less than 1,000 IU/ml, if they were negative for Aspergillus IgG, if they did not have current/recurrent respiratory tract infections, and if they did not receive treatment with intraconazole during the prior 8 months. The primary endpoint was a comparison between the Asthma Quality of Life Questionnaire (AQLQ) score between patients treated with itraconazole 200 mg (orally) twice daily and placebo. At 32 weeks, patients randomized to itraconazole had an increase in AQLQ of 0.85 compared with a decrease of 0.01 for the placebo group (P = 0.01). Similarly, AM peak flow, rhinitis score, and total serum IgE levels improved more in the itraconazole group. Follow-up four months after cessation of therapy showed a return of AQLQ toward baseline, yet preserved differences in IgE levels. The authors suggest that antifungal therapy may benefit patients with severe asthma and fungal sensitization. The improvement in symptoms and lung function could result from decreased fungal burden in the airway leading to decreased local airway inflammatory responses to aeroallergens.
Asthma Exacerbations and Decline in Lung Function
Asthma is characterized by reversible airflow obstruction. However, some patients progress and develop irreversible obstructive lung disease. One of the prime goals of asthma therapy is to prevent severe asthma-related events (SAREs) such as exacerbations. O'Byrne and colleagues used data from the START (inhaled steroid treatment as regular therapy in early asthma) (23) to evaluate the impact of asthma exacerbations and loss of lung function (24). The START trial enrolled 7,241 patients with asthma. Patients were randomized to once-daily budesonide or placebo. The primary outcome was time to first SARE defined as hospitalization, emergency room visit, or death due to asthma. Patients remained in the study for 3 years, with quarterly assessment of lung function. In total, 117 budesonide- and 198 placebo-treated patients experienced at least one exacerbation. The FEV1 at 3 years relative to baseline in the placebo-treated patients with an exacerbation was –6.44% compared with –2.43% in those without an exacerbation (P < 0.001). In the budesonide group, FEV1 was –2.48% in those with an exacerbation compared with –1.72% in those without an exacerbation (P = 0.57). The difference in magnitude of reduction from budesonide in patients who experienced at least one SARE compared with those who did not was statistically significant (P = 0.042). The authors concluded that severe asthma exacerbations are associated with more rapid decline in lung function, which was attenuated by low dose inhaled corticosteroid.
Asthma and Eosinophilia
Asthma is a heterogeneous disease. As our understanding of asthma phenotypes increases, it should become possible to target specific treatments at those patients most likely to benefit from therapy. As an example eosinophilia is present in some but not all patients with severe asthma. Interleukin-5 is an important mediator of airway eosinophilia. In a small study of 18 patients with persistent sputum eosinophilia despite prednisone therapy, Nair and colleagues evaluated the effect of mepolizumab, a mono-clonal antibody against interleukin-5 (25). Treatment with mepolizumab was steroid sparing and associated with lower sputum and blood eosinophils. In a larger study, Haldar and colleagues evaluated the impact of 1 year of therapy with mepolizumab for 61 patients with a history of refractory eosinophilic asthma with recurrent severe exacerbations (26). Treatment with mepolizumab was associated with fewer severe exacerbations (2.0 versus 3.4 mean exacerbations/yr, P = 0.02) and improved asthma quality of life score (0.55 versus 0.19, P = 0.02). There was no significant impact on asthma symptoms, FEV1, or airway hyperresponsiveness. These studies highlight the importance of targeting subgroups of patients most likely to respond to therapy in the evaluation and use of novel asthma therapies.
Asthma and Acetaminophen
Paracetamol (acetaminophen) is commonly used to relieve symptoms related to a variety of childhood illnesses. Beasley and colleagues (27) used data from Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) (28). This study provided data from questionnaires from 226,248 children aged 6 to 7 yr and represented 34 countries. Use of paracetamol in the first year of life for fever was associated with asthma symptoms (relative risk [RR], 1.76; 95% CI, 1.69–1.89), rhinoconjuctivitis (RR, 1.78; 95% CI, 1.69–1.86), and eczema (RR, 1.54; 95% CI, 1.47–1.61). The effect was present across the countries sampled. The association between paracetamol use and asthma symptoms does not prove causality. It could be that paracetamol use is the marker for respiratory tract infections, which could be causal. The study is also subject to potential recall bias. Further study is needed to further evaluate the potential relationship between paracetamol use and asthma.
Asthma Management Using Exhaled NO
Exhaled nitric oxide (NO) is a potential noninvasive biomarker of airway inflammation. Szefler and colleagues evaluated whether measures of exhaled NO, in addition to guideline-based management, could improve the effectiveness of asthma management compared with guideline-based clinical care alone (29). In a randomized, double-blind, multi-center, parallel-group trial, 546 patients with asthma were assigned to guideline-based standard therapy or guideline-based treatment modified by measurements of exhaled NO. In both groups, patients were seen every 6 weeks for 46 weeks. At each visit, symptoms were assessed and treatment adjustments were made using a standard protocol based on symptom control. In addition, the NO group had escalation of therapy by one additional step if exhaled NO level was high relative to that of control subjects. There was no difference in the mean number of days with asthma symptoms (1.93 in NO group versus 1.89 in placebo group, P = 0.8). Similarly, there were no differences in symptoms, pulmonary function, or asthma exacerbations. Although there was no effect in this study, it is possible that measurement of exhaled NO could be of benefit in specific asthma subgroups or in monitoring specific forms of treatment, especially therapy targeted at eosinophilic inflammation.
PLEURAL DISEASE
Richard W. Light
Vanderbilt University
Nashville, Tennessee
Pleural Fluid pH
Pleural fluid pH and glucose measures are important in the diagnosis and prognosis of pleural effusions related to infection, rheumatoid arthritis, esophageal rupture, and malignancy. Rahman and colleagues evaluated the impact of residual air, lidocaine, heparin, and delay in analysis up to 24 hours on these measures (30). A total of 92 fluid samples were evaluated from 81 patients. Three milliliters of fluid were immediately placed in a standard tube (syringe cleared of heparin and an airtight seal placed on the syringe), a lidocaine/air tube (1.0 ml of air and 0.2, 0.4, or 1.0 ml of lidocaine added), and a heparin tube (the 
0.4 ml of preloaded heparin was left in the tube). The presence of air significantly increased pH by 0.08 ± 0.07; in 71%, the presence of air changed the pH by greater than 0.05. The measured pH was decreased by lidocaine. The mean change in pH by 0.2 ml of lidocaine was –0.15 ± 0.09, –0.24 ± 0.11, and –0.43 ± 0.14 for 1.0 ml of lidocaine. Heparin did not significantly change pH. Pleural fluid pH increased over time and was statistically significant in samples tested over 1 hour after collection. At 1 hour, 13% of samples were changed by more than 0.05, 26% at 4 hours, and 68% by 24 hours. Pleural fluid glucose concentrations were not significantly altered by air, lidocaine, heparin, or delay in analysis. This study highlights the importance of excluding air and lidocaine from syringes, and that samples do not need to be placed on ice if analyzed within 1 hour.
Malignant Pleural Effusions: Treatment with Indwelling Catheter
Pleural effusions are a common complication of metastatic cancer. The most common options for treatment include palliative control of symptoms, repeated thoracentesis, and pleurodesis. Warren and colleagues retrospectively reviewed outcomes of Plerux catheters placed for patients with a symptomatic pleural effusion, an underlying malignancy with life expectancy greater than 30 days, and no underling complications such as coagulopathy, thrombocytopenia, or empyema (31). Catheters were placed using local anesthesia under sterile conditions in the operating room. Up to 1,500 cc of fluid were drained immediately. Subsequently patients used a vacuum drainage kit to remove 600 cc/day for the first 7 days and then to drain the pleural space every other day until less than 50 cc/day of fluid was present. At that time the patient was given the option to have the catheter removed. Overall, 173 of 295 (58.6%) of catheters were removed at a mean of 29.4 days. Reaccumulation of fluid causing dyspnea occurred in less than 1% of patients after catheter removal.
Malignant Pleural Effusion: Safety and Success of Talc Insufflation
Talc is commonly used for pleurodesis. There are variable reports regarding the safety of talc, particularly in terms of causing ARDS (32, 33). Janssen and colleagues studied 558 patients who received 4 g of talc insufflated at thoracoscopy performed by pulmonary physicians (34). The mean particle size of the talc was 24.6 µm. The study was performed at 14 medical centers in Europe and South Africa. A chest X-ray was performed after 24 hours and requirements for supplemental oxygen and temperature were noted twice daily. No patients developed acute respiratory distress syndrome, although seven developed new infiltrates. Infiltrates were attributed to cardiogenic pulmonary edema, re-expansion pulmonary edema, infection, and non-ARDS respiratory failure. Increase in temperature and oxygen requirements were common. These data suggest that pleurodesis with large particle talc is safe. Further study of the safety of small particle talc is required. In a separate study, Aydogmus and colleagues retrospectively evaluated factors associated with the success of talc pleurodesis (35). Data from 113 symptomatic malignant pleural effusions in 103 patients were evaluated. Bedside pleurodesis was performed in 86 (77.5%) cases. Four to eight grams of "asbestos-free" sterile talc was used in 81 cases; particle size was not noted. Talc was re-administered if fluid reaccumulated. Success was defined as absence of effusion at 3 weeks after termination of drainage, partial success was defined as the presence of a localized effusion that did not progress, cause symptoms, or require drainage. Eight patients were not available at 21 days follow up due to death (n = 4), ARDS (n = 2), end-stage disease (n = 2), and loss to follow up (n = 4), leaving a final study group of 73. Complete success was seen in 49 cases and a partial response in 11 cases. Eleven cases required a second administration of talc. Success was higher if the procedure was performed within 30 days of diagnosis, if spontaneous expansion occurred after drainage and if the amount of drainage after tube insertion was less than 200 ml/day.
Dasatinib Causes Pleural Effusions
Imatinib and dasatinib are inhibitors of the abl and Src family of kinases. These agents are used to treat patients in the chronic phase of chronic myelogenous leukemia. Dasatinib is more potent and approved for use in patients with imatinib failure. Quintas-Cardama and colleagues retrospectively evaluated 138 patients with CML treated with dasatinib after imatinib failure (36). Pleural effusion was present in 48 (35%) patients. Effusions were predominantly bilateral (79%) and occupied more than 25% of the hemithorax in 17%. Fluid analysis from 9 of the 10 patients that required thoracentesis revealed an exudate in 78% and marked lymphocytosis (median 90%, range 69–100%). Malignant cells or infection were not present. Discontinuation or dose reduction of dasatinib resulted in slow resolution of the effusion. Some patients were treated with steroids which seemed to result in more rapid improvement compared with cessation of treatment alone. The lymphocytic nature of the fluid suggests that an immune-mediated mechanism may be responsible.
FOOTNOTES
This is the fourth in a series of four executive summaries of the Clinical Year in Review Sessions presented at the American Thoracic Society International Conference in May, 2009. The main topics of each talk have been abstracted by the session chair based on the annotated bibliography provided by each presenter.
Conflict of Interest Statement: K.R.F. served as a consultant for Boehringer Ingelheim $5,001–$10,000, Gilead $1,001–$5,000, Neopharm $10,001–$50,000, and served on the Board or Advisory Board for Fibrogen and Actelion $1,001–$5,000. He received lecture fees from Pfizer $1,001–$5,000, Boehringer Ingelheim $5,001–$10,000, GlaxoSmithKline $10,001–$50,000, and Ortho McNeil $1,001–$5,000. He received grant support from Intermune $100,001–more and he receives royalties from Up to Date $10,000–$50,000.
(Received in original form July 14, 2009; accepted in final form July 21, 2009)
REFERENCES
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
