Chest. 2008;133(6):1293-1295. doi:10.1378/chest.08-0782

The American College of Chest Physicians (ACCP) guidelines addressing antithrombotic therapy, first published in 1986,1 have been updated about every 3 years. The eighth edition of the guidelines [now called “Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)]” is published as a special supplement of CHEST this month.2 Over the past 2 decades, these guidelines have adapted to trends in evidence-based medicine and helped to raise the standards for guideline methodology.38 The eighth edition has, judging by the numerous daily requests for the publication date, been one of the most anxiously anticipated products of the ACCP.

Chest. 2008;133(6):1295-1296. doi:10.1378/chest.07-2910

Acute lung injury (ALI), a major cause of morbidity and mortality worldwide, remains a challenge for clinicians and scientists despite decades of investigation. Although substantial progress has been made in understanding the pathogenesis of ALI and, recently, mortality has been decreased by reevaluating the approach to mechanical ventilation in patients with the syndrome, there are still major voids in our knowledge. To date, we are able to predict neither who will acquire ALI nor who will survive, and there are not yet any beneficial pharmacologic interventions. Within the last decade, however, a number of factors have been identified that help to explain the apparent lack of progress and provide opportunities for the development of targeted therapeutic interventions. These include the recognition that the definition of the syndrome,1 patient variables, and environmental interactions are all critically important in this syndrome. Not only do the incidence and outcome from ALI vary with specific risk factors including sepsis and trauma, and pulmonary vs nonpulmonary factors, but preexisting factors including age, gender, and race, and comorbid conditions such as diabetes and alcohol abuse also impact incidence and outcome.24 The tremendous heterogeneity that exists among patients at risk for and with ALI likely explains the apparent lack of benefit from any of the pharmacologic interventions that have been studied. In light of the significant differences in biomarkers in these various patient groups,5 it makes sense that one therapy is not likely to benefit all; rather, a new approach that allows for the development of targeted therapeutic interventions is more likely to be successful.

Topics: iron , genetics
Chest. 2008;133(6):1296-1298. doi:10.1378/chest.08-0455

COPD is among the top 10 conditions that affect the world population.1 Its prevalence has risen by 41% since 1982, and its age-adjusted mortality rate increased by > 100% between 1970 and 2002. These trends are projected to continue into the foreseeable future.2 Dissimilar to other major causes of mortality, such as ischemic heart disease, stroke, and HIV/AIDs, there is a dearth of effective interventional strategies that can modify the natural course of COPD.3 In particular, to our knowledge, there are no known pharmacologic therapies that can reduce the progressive and relentless decline in lung function that characterizes COPD. A major impediment in drug discoveries has been the lack of lung-specific biomarkers that can be used as an intermediate end point for short-term (and less costly) clinical trials. An ideal biomarker is one that (1) has biological plausibility in terms of its role in the pathogenesis of the disease, (2) is associated with a clinically important outcome such as mortality, and (3) can be modified (by an effective intervention) to change the target outcome of interest.4 In COPD, we have no established biomarkers that fulfill all of these criteria.

Chest. 2008;133(6):1298-1300. doi:10.1378/chest.07-3099

The practice of withholding life-sustaining treatments in the ICU typically occurs when the conditions of one or both of two premises are met. The first premise is that the prognosis for survival is poor, even with life-sustaining treatment, and that withholding these treatments will not affect the ultimate outcome. The second premise is that the potential benefits of treatment, in terms of quantity and quality of life, are not, in the judgment of the patient (or of the surrogate decision maker) worth the burden of these treatments.

Second Opinion

Chest. 2008;133(6):1301. doi:10.1378/chest.133.6.1301


Chest. 2008;133(6):1302-1311. doi:10.1378/chest.07-1117

Background: Abnormal plasma and lung iron mobilization is associated with the onset and progression of ARDS and is detectable in specific at-risk populations. Patients with ARDS also have pronounced oxidative and nitrosative stress that can be catalyzed and thereby aggravated by the bioavailability of redox active iron. ARDS of pulmonary and extrapulmonary origin may differ pathophysiologically and require different ventilatory strategies. Evidence suggests that genetic predisposition is relevant to the pathogenesis of ARDS. We therefore explored the hypothesis that polymorphisms from a panel of genes encoding iron-metabolizing proteins determine susceptibility to ARDS.

Methods: Retrospective case-control study conducted at the adult ICUs of two university hospitals. Patients with ARDS (n = 122) and healthy control subjects (n = 193) were genotyped. Sequence-specific primer polymerase chain reaction was used to genotype selected biallelic single-nucleotide polymorphisms. An audit of the patient database was conducted, and 104 of the 122 ARDS patients were eligible for the final data analysis.

Results: Preliminary analysis indicated differences between ARDS and healthy control subjects in the incidence of polymorphism of the gene encoding ferritin light chain. Subgroup analysis indicated the prevalence of ferritin light-chain gene −3381GG homozygotes was increased in patients with ARDS of extrapulmonary origin compared to healthy control subjects. Secondly, a common haplotype in the heme oxygenase 2 gene was reduced in patients with ARDS compared to healthy control subjects and was more evident in those with ARDS of direct or pulmonary etiology.

Conclusions: These results provide preliminary evidence to suggest a distinction in the genetic background of the subpopulations studied, inferring that the ferritin light-chain gene genotype confers susceptibility to ARDS, while the heme oxygenase 2 haplotype is protective against the onset of the syndrome. Such data support further previous findings that suggest abnormalities in iron handling resulting in redox imbalance are implicated in the pathogenesis of ARDS.

Chest. 2008;133(6):1312-1318. doi:10.1378/chest.07-1500

Background: The effect on long-term mortality of decisions made to withhold life-supporting therapies (LST) for critically ill patients is unclear. We hypothesized that mortality 60 days after ICU admission is not influenced by a decision to withhold use of LST in the context of otherwise providing all indicated care.

Methods: We studied 2,211 consecutive, initial admissions to the adult, medical ICU of a university-affiliated teaching hospital. To achieve balanced groups for comparing outcomes, we created a multivariable regression model for the probability (propensity score [PS]) of having an order initiated in the ICU to withhold LST. Each of the 201 patients with such an order was matched to the patient without such an order having the closest PS; mortality rates were compared between the matched pairs. Cox survival analysis was performed to extend the main analysis.

Results: The matched pairs were well balanced with respect to all of the potentially confounding variables. Sixty days after ICU admission, 50.5% of patients who had an order initiated in the ICU to withhold life support had died, compared to 25.8% of those lacking such orders (risk ratio, 2.0; 95% confidence interval, 1.5 to 2.6). Survival analysis indicated that the difference in mortality between the two groups continued to increase for approximately 1 year.

Conclusion: Contrary to our hypothesis, decisions made in the ICU to withhold LST were associated with increased mortality rate to at least 60 days after ICU admission.

Variation in ICU Risk-Adjusted Mortality*: Impact of Methods of Assessment and Potential Confounders
Chest. 2008;133(6):1319-1327. doi:10.1378/chest.07-3061

Background: Federal and state agencies are considering ICU performance assessment and public reporting; however, an accurate method for measuring performance must be selected. In this study, we determine whether a substantial variation in ICU mortality performance still exists in modern ICUs, and compare the predictive accuracy, reliability, and data burden of existing ICU risk-adjustment models.

Methods: A retrospective chart review of 11,300 ICU patients from 35 California hospitals from 2001 to 2004 was performed. We calculated standardized mortality ratios (SMRs) for each hospital using the mortality probability model III (MPM0 III), the simplified acute physiology score (SAPS) II, and the acute physiology and chronic health evaluation (APACHE) IV risk-adjustment models. We compared discrimination, calibration, data reliability, and abstraction time for the models.

Results: Regardless of the model used, there was a large variation in SMRs among the ICUs studied. The discrimination and calibration were adequate for all risk-adjustment models. APACHE IV had the best discrimination (area under the receiver operating characteristic curve [AUC], 0.892) compared to MPM0 III (AUC, 0.809), and SAPS II (AUC, 0.873; p < 0.001). The models differed substantially in data abstraction times, as follows: MPM0III, 11.1 min (95% confidence interval [CI], 8.7 to 13.4); SAPS II, 19.6 min (95% CI, 17.0 to 22.2); and APACHE IV, 37.3 min (95% CI, 28.0 to 46.6).

Conclusions: We found substantial variation in the ICU risk-adjusted mortality rates that persisted regardless of the risk-adjustment model. With unlimited resources, the APACHE IV model offers the best predictive accuracy. If constrained by cost and manual data collection, the MPM0 III model offers a viable alternative without a substantial loss in accuracy.

Chest. 2008;133(6):1328-1335. doi:10.1378/chest.07-2702

Objectives: We document clinicians’ stated blood glucose control practice patterns in North American pediatric and adult ICUs.

Methods: Using a Web-based self-administered questionnaire, we conducted a nationwide survey of North American pediatric and adult ICUs. Participants included ICU medical directors, nurses, fellows in training, and attending intensivists from participating ICUs in three critical care research networks.

Measurements and main results: Item generation and item selection were performed according to standard scientific survey methods. Questions were designed to describe clinicians’ perceptions about glucose control practices. The questionnaire topics included the following: respondent characteristics; ICU description; hyperglycemia; hypoglycemia; and glucose measurement. The institutional response rate was 96% (50 of 52 institutions). The clinician response rate was 58% (163 of 282 physicians). Adult ICU clinicians defined hyperglycemia (120 mg/dL [6.2 mmol/L]) at a lower threshold than pediatric ICU clinicians (150 mg/dL [8.3 mmol/L]). Hypoglycemia was defined similarly by both groups (median, ≤ 60 mg/dL [3.3 mmol/L]; range, 40 to 80 mg/dL [2.2 to 4.4 mmol/L]). More pediatric ICU clinicians (84.5%) than adult ICU clinicians (59.1%) considered hypoglycemia to be more dangerous than hyperglycemia. A larger percentage of adult ICU clinicians (82.5%) than pediatric ICU clinicians (49.3%) preferred a target blood glucose level between 80 and 110 mg/dL (4.4 to 6.1 mmol/L). Clinical algorithms for glucose management varied among clinicians and across institutions.

Conclusions: Blood glucose control with insulin is used frequently for critically ill adults and children. A wide variation in practice exists in blood glucose targets, hyperglycemia and hypoglycemia definitions, and decision algorithms among North American adult and pediatric ICUs.

Original Research: COPD

Chest. 2008;133(6):1336-1343. doi:10.1378/chest.07-2433

Background: Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease.

Objective: To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease.

Methods: In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao2), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality.

Results: During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival.

Conclusions: In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV1, IC/TLC ratio < 0.25, and Pao2. Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.

Chest. 2008;133(6):1344-1353. doi:10.1378/chest.07-2245

Background: Despite overwhelming data that cigarette smoking causes COPD, only a minority of long-term smokers are affected, strongly suggesting that genetic factors modify susceptibility to this disease. We hypothesized that individual variations exist in the response to cigarette smoking, with variability among smokers in expression levels of protective/susceptibility genes.

Methods: Affymetrix arrays and quantitative polymerase chain reaction were used to assess the variability of gene expression in the small airway epithelium obtained by fiberoptic bronchoscopy of 18 normal nonsmokers, 18 normal smokers, and 18 smokers with COPD.

Results: We identified 201 probe sets representing 152 smoking-responsive genes that were significantly up-regulated or down-regulated, and assessed the coefficient of variation in expression levels among the study population. Variation was a reproducible property of each gene as assessed by different microarray probe sets and real-time polymerase chain reaction, and was observed in both normal smokers and smokers with COPD. Greater individual variability was found in smokers with COPD than in normal smokers. The majority of these highly variable smoking-responsive genes were in the functional categories of signal transduction, xenobiotic degradation, metabolism, transport, oxidant related, and transcription. A similar pattern of the same highly variable genes was observed in an independent data set.

Conclusions: We propose that genetic diversity is likely within this subset of genes, with highly variable individual-to-individual responses of the small airway epithelium to smoking, and that this subset of genes represents putative candidates for assessment of susceptibility/protection from disease in future gene-based epidemiologic studies of smokers’ risk for COPD.

Chest. 2008;133(6):1354-1359. doi:10.1378/chest.07-2685

Background: Increased right ventricular afterload leads to left ventricular diastolic dysfunction due to ventricular interdependence. Increased right ventricular afterload is frequently present in patients with COPD. The purpose of this study was to determine whether left ventricular diastolic dysfunction could be detected in COPD patients with normal or elevated pulmonary artery pressure (PAP).

Methods: Twenty-two patients with COPD and 22 matched control subjects underwent pulsed Doppler echocardiography. Left ventricular systolic dysfunction and other causes of left ventricular diastolic dysfunction (eg, coronary artery disease) were excluded in all patients and control subjects. PAP was measured invasively in 13 patients with COPD.

Results: The maximal atrial filling velocity was increased and the early filling velocity was decreased in patients with COPD compared to control subjects. The early flow velocity peak/late flow velocity peak (E/A) ratio was markedly decreased in patients with COPD compared to control subjects (0.79 ± 0.035 vs 1.38 ± 0.069, respectively; p < 0.0001), indicating the presence of left ventricular diastolic dysfunction. The atrial contribution to total left diastolic filling was increased in patients with COPD. This was also observed in COPD patients with normal PAP, as ascertained using a right heart catheter. The atrial contribution to total left diastolic filling was further increased in COPD patients with PAP. PAP correlated with the E/A ratio (r = −0.85; p < 0.0001).

Conclusions: Left ventricular diastolic dysfunction is present in COPD patients with normal PAP and increases with right ventricular afterload.

Chest. 2008;133(6):1360-1366. doi:10.1378/chest.07-2543

Background: COPD is associated with an increased risk of peptic ulcer disease, but limited data exist on whether COPD influences short-term mortality among patients with bleeding and a perforated peptic ulcer. We examined the association between COPD and 30-day mortality following bleeding and perforation of a peptic ulcer.

Methods: We identified all patients who had been hospitalized with a first-time diagnosis of peptic ulcer perforation (n = 2,033) or bleeding (n = 7,486) in northern Denmark between 1991 and 2004. Information on COPD, comorbidities, and filled prescriptions was obtained from medical databases. Mortality was ascertained using the Danish Civil Registration System. We computed the cumulative 30-day mortality rates for ulcer patients with COPD and for other ulcer patients, and used regression analysis to obtain the 30-day mortality rate ratios (MRRs), controlling for potential confounding factors.

Results: Among patients who were hospitalized with perforated peptic ulcers, 218 (10.7%) had previously been hospitalized with COPD. The 30-day mortality rate was 44.0% among perforated ulcer patients with COPD vs 25.5% among other ulcer patients (adjusted MRR, 1.48; 95% confidence interval [CI], 1.18 to 1.85). Among patients hospitalized with a bleeding peptic ulcer, 759 (10.1%) had previously been hospitalized with COPD. The 30-day mortality rate was 16.5% among bleeding peptic ulcer patients with COPD vs 10.8% among other ulcer patients (adjusted MRR, 1.38; 95% CI, 1.14 to 1.68). The use of oral glucocorticoids among COPD patients was associated with higher MRRs for both perforated and bleeding peptic ulcers.

Conclusions: COPD substantially increased 30-day mortality among patients with bleeding and perforated peptic ulcers.

Original Research: ASTHMA

Secondhand Tobacco Smoke in Children With Asthma*: Sources of and Parental Perceptions About Exposure in Children and Parental Readiness To Change
Chest. 2008;133(6):1367-1374. doi:10.1378/chest.07-2369

Background: Secondhand smoke triggers childhood asthma. Understanding sources of exposure, parental beliefs about exposure, and readiness to change that exposure are important for designing smoke exposure reduction interventions.

Methods: As part of screening for a clinical trial of a smoke exposure reduction intervention, 519 smoke-exposed children 3 to 12 years old with asthma provided urine specimens for cotinine testing, and their primary caregivers completed questionnaires.

Results: The urine cotinine to creatinine ratio (CCR) was lowest if neither the primary caregiver nor day-care provider smoked (mean CCR, 14.0; SD, 14.4), greater if either smoked (mean CCR, 22.2; SD, 21.3; and mean, CCR, 26.3; SD, 22.2, respectively), and greatest if both smoked (mean CCR, 39.6; SD, 27.5; p < 0.01). Parental perception of their child’s exposure was weakly associated with the child’s CCR (r2 = 0.11, p < 0.001). Most parents (58.3%) reported that tobacco smoke exposure had small/no negative effect on their child’s asthma. Substantial proportions of those for whom a specific exposure reduction action was relevant were classified as contemplating, preparing, or had recently taken action to reduce their child’s exposure, including smoking cessation (61.3%), keeping the child out of smoke-exposed places (72.7%), and making the child’s home (49.2%) and areas out of the home smoke free (66.9%).

Conclusions: Smoking by the primary caregiver and day-care provider are important sources of exposure for children with asthma. Parental assessment of their child’s exposure is associated with biologically confirmed exposure but cannot be relied on to assess that exposure. Although the harm of smoke exposure was frequently underestimated, many parents appeared receptive to considering action to reduce their child’s exposure.

Trial registration: Clinicaltrials.gov. Identifier: NCT00217958.

Original Research: SLEEP MEDICINE

Chest. 2008;133(6):1375-1380. doi:10.1378/chest.07-3035

Background: Cheyne-Stokes respiration (CSR) and central sleep apnea (CSA) are common in patients with left-heart failure. We investigated the hypothesis that sleep-disordered breathing is also prevalent in patients with right ventricular dysfunction due to pulmonary hypertension (PH).

Methods: We studied 38 outpatients (median age, 61 years; quartiles, 51 to 72) with pulmonary arterial hypertension (n = 23) or chronic thromboembolic PH (n = 15). New York Heart Association (NYHA) class was II to IV, and median 6-min walk distance was 481 m (quartiles, 429 to 550). In-laboratory polysomnography (n = 22) and ambulatory cardiorespiratory sleep studies (n = 38) including pulse oximetry were performed. Quality of life and sleepiness by the Epworth sleepiness score were assessed.

Results: The median apnea/hypopnea index was 8 events/h (quartiles, 4 to 19), with 8 central events (quartiles, 4 to 17), and 0 obstructive events (quartiles, 0 to 0.3) per hour. Seventeen patients (45%) had ≥ 10 apnea/hypopnea events/h. Comparison of 13 patients with ≥ 10 CSR/CSA events/h with 21 patients with < 10 CSR/CSA events/h (excluding 4 patients with ≥ 10 obstructive events/h from this analysis) revealed no difference in regard to hemodynamics, NYHA class, and Epworth sleepiness scores. However, patients with ≥ 10 CSR/CSA events/h had a reduced quality of life in the physical domains. Ambulatory cardiorespiratory sleep studies accurately predicted ≥ 10 apnea/hypopnea events/h during polysomnography in patients who underwent both studies (area under the receiver operating characteristic curve, 0.93; SE ± 0.06; p = 0.002). The corresponding value for pulse oximetry was 0.63 ± 0.14 (p = not significant).

Conclusions: In patients with PH, CSR/CSA is common, but obstructive sleep apnea also occurs. Sleep-related breathing disorders are not associated with excessive sleepiness but affect quality of life. They should be evaluated by polysomnography or cardiorespiratory sleep studies because pulse oximetry may fail to detect significant sleep apnea.

Original Research: CYSTIC FIBROSIS

Chest. 2008;133(6):1381-1387. doi:10.1378/chest.07-2437

Background: Limited data exist about the molecular types of methicillin-resistant Staphylococcus aureus (MRSA) strains found in children with cystic fibrosis (CF). We sought to characterize MRSA strains from these patients and compare them with MRSA strains from non-CF pediatric patients.

Methods: All MRSA isolates were collected prospectively at Children’s Medical Center in Dallas, TX, and the University of Chicago Comer Children’s Hospital in 2004 to 2005. All CF MRSA isolates underwent susceptibility testing, multilocus sequence typing, Panton-Valentine leukocidin gene detection (pvl+), and staphylococcal chromosome cassette mec (SCCmec) typing.

Results: A total of 22 of 34 MRSA isolates (64.7%) from patients with CF belonged to clonal complex (CC) 5 and contained SCCmec II, so-called health-care associated MRSA (HA-MRSA) strains. Nine of 34 MRSA strains (26.5%) were CC 8, and contained SCCmec IV, so-called community-associated MRSA (CA-MRSA) strains. The CA-MRSA strains tended to be isolated from newly colonized CF patients. In contrast, CC8 isolates predominated among the non-CF patients (294 of 331 patients; 88.8%). MRSA isolates from children with CF were more likely to be resistant to clindamycin (65% vs 19%, respectively) and ciprofloxacin (62% vs 17%, respectively) compared with strains from non-CF patients (p < 0.001). There was no difference in the rate of pvl+ isolate recovery from children with CF undergoing a surveillance culture (7 of 23 children) compared with those with pulmonary exacerbation (3 of 11 children; p = 1.0).

Conclusions: Both CA-MRSA (CC8) isolates and HA-MRSA (CC5) isolates populate the respiratory tracts of children with CF. HA-MRSA isolates predominated, but CA-MRSA strains predominated among CF patients with newly acquired MRSA strains and among the non-CF patients. The presence of CA-MRSA strains in children with CF was not associated with exacerbation or necrotizing pneumonia.

Chest. 2008;133(6):1388-1396. doi:10.1378/chest.07-2294

Background: The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health. To this end, this study examined the efficacy and safety of therapy with inhaled mannitol over a 2-week period.

Methods: This was a randomized, double-blind, placebo-controlled, crossover study. Thirty-nine subjects with mild-to-moderate CF lung disease inhaled 420 mg of mannitol or placebo twice daily for 2 weeks. Following a 2-week washout period, subjects were entered in the reciprocal treatment arm. Lung function, respiratory symptoms, quality of life, and safety were assessed.

Results: Mannitol treatment increased FEV1 from baseline by a mean of 7.0% (95% confidence interval [CI], 3.3 to 10.7) compared to placebo 0.3% (95% CI, − 3.4 to 4.0; p < 0.001). The absolute improvement with mannitol therapy was 121 mL (95% CI, 56.3 to 185.7), which was significantly more than that with placebo (0 mL; 95% CI, − 64.7 to 64.7). The forced expiratory flow in the middle half of the FVC increased by 15.5% (95% CI, − 6.5 to 24.6) compared to that with placebo (increase, 0.7%; 95% CI, − 8.3 to 9.7; p < 0.02). The safety profile of mannitol was adequate, and no serious adverse events related to treatment were observed.

Conclusions: Inhaled mannitol treatment over a period of 2 weeks significantly improved lung function in patients with CF. Mannitol therapy was safe and well tolerated.

Trial registration: Clinical Trials.gov Identifier: NCT00455130


Chest. 2008;133(6):1397-1401. doi:10.1378/chest.08-0255

Background: Dysphagia can lead to aspiration of oral feeds, thus causing pneumonia. Dysphagia is diagnosed by assessing the ability to swallow barium test feeds (BTF) of different viscosities. Dysphagia diet foods (DDF) are thickened as recommended by the National Dysphagia Diet (NDD) guidelines. To our knowledge, there are no published data evaluating if the viscosity of BTF or commercial DDF meet NDD guidelines.

Methods: A TA1000 rheometer (TA Instruments; New Castle, DE) measured dynamic viscosity of BTF and DDF using creep transformation under controlled stress. Thin DDF studied included Plus Energy Drink (Boost; Novartis/Nestle; Fremont, MI) and Instant Breakfast (Carnation; Wilkes-Barre, PA) and nectar- and honey-thick DDF from Hormel (Hormel Health Labs; Savannah, GA) and Novartis (Novartis/Nestle). The BTF studied were thin, nectar-, and honey-thick Polibar barium suspension or Varibar (E-Z-EM, Inc.; Lake Success, NY). We measured batch-to-batch variability in the viscosity of DDF, with and without shaking, and after 2 h at ambient temperature at a shear rate chosen to match natural swallowing.

Results: We observed the following: (1) DDF: the viscosity of honey-thick DDF was consistent with NDD guidelines, but other products were not. All products had minimal change in viscosity over 2 h. Boost thin liquid had > 300% increase in viscosity after shaking. (2) BTF: thin barium had a viscosity consistent with NDD guidelines. The nectar- and honey-thick Polibar BTFs were thixotropic and had unacceptably high viscosity. Varibar BTFs were not thixotropic but were more viscous than the NDD guidelines.

Conclusions: There was a poor relationship between the viscosity of DDF and BTF. The viscosity of BFTs is much greater than the correspondingly named diet foods and the NDD guidelines. This can place patients at significant risk for oral aspiration.

Original Research: LUNG CANCER

Pulmonary Nodular Ground-Glass Opacities in Patients With Extrapulmonary Cancers*: What is Their Clinical Significance and How Can We Determine Whether They Are Malignant or Benign Lesions?
Chest. 2008;133(6):1402-1409. doi:10.1378/chest.07-2568

Background: The clinical significance of pulmonary nodular ground-glass opacities (NGGOs) in patients with extrapulmonary cancers is not known, although there is an urgent need for study on this topic. The purpose of this study, therefore, was to investigate the clinical significance of pulmonary NGGOs in these patients, and to develop a computerized scheme to distinguish malignant from benign NGGOs.

Methods: Fifty-nine pathologically proven pulmonary NGGOs in 34 patients with a history of extrapulmonary cancer were studied. We reviewed the CT scan characteristics of NGGOs and the clinical features of these patients. Artificial neural networks (ANNs) were constructed and tested as a classifier distinguishing malignant from benign NGGOs. The performance of ANNs was evaluated with receiver operating characteristic analysis.

Results: Twenty-eight patients (82.4%) were determined to have malignancies. Forty NGGOs (67.8%) were diagnosed as malignancies (adenocarcinomas, 24; bronchioloalveolar carcinomas, 16). Among the rest of the NGGOs, 14 were atypical adenomatous hyperplasias, 4 were focal fibrosis, and 1 was an inflammatory nodule. There were no cases of metastasis appearing as NGGOs. Between malignant and benign NGGOs, there were significant differences in lesion size; the presence of internal solid portion; the size and proportion of the internal solid portion; the lesion margin; and the presence of bubble lucency, air bronchogram, or pleural retraction (p < 0.05). Using these characteristics, ANNs showed excellent accuracy (z value, 0.973) in discriminating malignant from benign NGGOs.

Conclusions: Pulmonary NGGOs in patients with extrapulmonary cancers tend to have high malignancy rates and are very often primary lung cancers. ANNs might be a useful tool in distinguishing malignant from benign NGGOs.


Chest. 2008;133(6):1410-1414. doi:10.1378/chest.07-2984

Background: Pulmonary vasoconstriction in response to hypoxia is unusual inasmuch as local exposure of nonpulmonary vasculature to hypoxia results in vasodilation. It has been suggested that pulmonary artery smooth-muscle cells may relax in response to intracellular generation of reactive oxygen species (ROS) and that the production of ROS decreases under hypoxia. However, other workers report increased ROS production in human pulmonary artery smooth-muscle cells (HPASMC) during hypoxia.

Methods: Using dihydrodichlorofluorescein diacetate, dihydroethidium, and Amplex Red (Molecular Probes; Eugene, OR), we estimated ROS generation by confluent primary cultures of HPASMC and human coronary artery smooth-muscle cells (HCASMC) under normoxia (20%) and acute hypoxia (5%).

Results: All three assay systems showed that HPASMC production of ROS is decreased under hypoxia and to a greater extent than the decrease in ROS production by HCASMC. A substantially greater percentage of normoxic ROS production by HPASMC is mitochondrial (> 60%) compared to HCASMC (< 30%).

Conclusions: These results support the conclusion that ROS generation decreases, rather than increases, in HPASMC during hypoxia. However, as ROS production also decreases in HCASMC during hypoxia, the reason for the opposite change in vascular tone is not yet apparent.


Chest. 2008;133(6):1415-1420. doi:10.1378/chest.07-2193

Background: A two-step procedure using a tuberculin skin test (TST) followed by an interferon (IFN)-γ assay in cases in which the TST result is positive has been advocated to screen for latent tuberculosis infection. However, TST could also boost the in vitro immune response. In this study, we evaluated the effect of TST on the results of the IFN-γ assay.

Methods: Our study included 84 health-care workers who had been working in the department of pulmonary medicine for > 1 year. First, a whole-blood IFN-γ assay was performed, and then the TST was applied. Two to 4 weeks later, a follow-up IFN-γ assay was performed. A commercially available IFN-γ assay (QuantiFERON-TB GOLD; Cellestis Ltd; Carnegie, VIC, Australia) was used.

Results: Valid TST results were available in 82 individuals because 2 participants refused to undergo the TST after the IFN-γ assay. The TST result was positive in 36 of 82 participants (42.7%), and the IFN-γ assay was positive in 16 of 82 participants (19.5%). The overall agreement between the two tests was 67.5% (κ = 0.31; 95% confidence interval, 0.22 to 0.40). The IFN-γ levels increased significantly from 0.05 to 0.19 (p = 0.011), and 3 of 18 participants (16.7%) had conversion of their IFN-γ assay results in the TST-positive group. However, in the TST-negative group, the IFN-γ levels did not change after the TST.

Conclusion: The agreement between the results of the TST and the IFN-γ assay was low, and IFN-γ level could be influenced by the TST, in the TST-positive population, when a follow-up IFN-γ assay is performed 2 to 4 weeks later.


Chest. 2008;133(6):1421-1425. doi:10.1378/chest.07-0960

Study aim: To evaluate the feasibility of combined oximetry (pulse oximetric saturation [Spo2]) and cutaneous capnography (transcutaneous carbon dioxide tension [Ptcco2]) for oxygen titration in patients requiring long-term oxygen therapy.

Methods: Twenty patients with obstructive or restrictive lung disease underwent oxygen titration using a combined cutaneous oximetry-capnography sensor. The goal of titration was to achieve an oxygen saturation of > 90% without a significant rise in carbon dioxide. Spo2 and Ptcco2 measurements at the end of titration were compared with blood gas levels using Bland-Altman analysis and linear regression analysis.

Results: The mean (± SE of the estimate) Pao2 while breathing room air was 53.2 ± 8.1 mm Hg and increased to 75.9 ± 13.3 mm Hg with oxygen supplementation (p < 0.0001). The mean Paco2 was 45.9 ± 8.7 mm Hg at baseline and 47.8 ± 9.0 mm Hg after oxygen titration (p = 0.003). Bland-Altman analysis for comparison of Ptcco2 and Paco2 showed a bias of 0.86 mm Hg with a precision of 3.48 mm Hg. Bland-Altman analysis for the comparison of Spo2 and arterial oxygen saturation showed a bias of 0.14% with a precision of 1.13%.

Conclusion: Combined oximetry and cutaneous capnography is feasible during oxygen titration in patients needing long-term oxygen therapy. This noninvasive approach has the potential to reduce the number of arterial blood gas samplings performed.

Original Research: SARCOIDOSIS

Cardiac Involvement in Patients with Sarcoidosis*: Diagnostic and Prognostic Value of Outpatient Testing
Chest. 2008;133(6):1426-1435. doi:10.1378/chest.07-2784

Background: Cardiac sarcoidosis (CS) causes substantial morbidity and sudden death. Early diagnosis and risk stratification are warranted.

Methods: Ambulatory patients with sarcoidosis were interviewed to determine whether they experienced palpitations, syncope, or presyncope, and were evaluated with ECG, Holter monitoring, and echocardiography (transthoracic echocardiogram [TTE]). Those with symptoms or abnormal results were studied with cardiac MRI (CMRI) or positron emission tomography (PET) scanning. The diagnosis of CS was based on abnormalities detected by these imaging studies. Patients with CS were referred for risk stratification by electrophysiology study (EPS).

Results: Among the 62 patients evaluated, the prevalence of CS was 39%. Patients with CS had more cardiac symptoms than those without CS (46% vs 5%, respectively; p < 0.001), and were more likely to have abnormal Holter monitoring findings (50% vs 3%, respectively; p < 0.001) and TTE findings (25% vs 5%, respectively; p = 0.02). The degree of pulmonary impairment did not predict CS. Two of the 17 patients who underwent EPS had abnormal test findings and received implantable cardioverter-defibrillators. No patients died, had ventricular arrhythmias that triggered defibrillator therapy, or had heart failure develop during almost 2 years of follow-up. This diagnostic approach was more sensitive than the established criteria for identifying CS.

Conclusion: CS is common among patients with sarcoidosis. A structured clinical assessment incorporating advanced cardiac imaging with PET scanning or CMRI is more sensitive than the established criteria for the identification of CS. Sarcoidal lesions seen on CMRI or PET scanning do not predict arrhythmias in ambulatory patients with preserved cardiac function, who appear to be at low risk for short-term mortality.

Original Research: PLEURAL DISEASE

Chest. 2008;133(6):1436-1441. doi:10.1378/chest.07-2232

Objectives: Chyle is a noninflammatory, lymphocyte-predominant fluid that may cause a pleural effusion as a consequence of thoracic duct leakage into the pleural space. Although chyle is reported to have protein concentrations in the transudative range, chylous effusions are typically exudative, as defined by the standard criteria. We hypothesized that chylous effusions from a thoracic duct leak alone have low lactate dehydrogenase (LDH) concentrations due to the absence of inflammation and are lymphocyte-predominant, protein-discordant exudates. Consequently, pleural effusions that do not meet these criteria but with triglyceride concentrations of > 110 mg/dL or are positive for chylomicrons should be associated with other diagnoses contributing to pleural fluid formation.

Study design: Retrospective.

Methods: The pleural fluid analyses of 876 consecutive thoracenteses were reviewed. All cases with a triglyceride concentration of > 110 mg/dL or the presence of chylomicrons were retrieved. The effusions were then classified as transudates, concordant exudates, protein-discordant exudates, and LDH-discordant exudates, and according to lymphocyte predominance (> 50%). The causes of these pleural effusions were determined after the review of the medical record.

Results: Twenty-two pleural effusions had elevated triglyceride concentrations and/or were positive for chylomicrons. Eleven effusions were lymphocyte-predominant, protein-discordant exudates, and two of these were associated with chylous ascites. The remaining effusions were transudates (n = 7) or concordant exudates (n = 4); all were associated with conditions known to cause pleural effusion apart from chyle leakage.

Conclusion: Chylous effusions caused solely by conditions known to cause chylothorax were lymphocyte-predominant, protein-discordant exudates. Protein concentrations in the transudative range or elevated LDH concentrations were associated with a coexisting condition that may impact the management of these chylous effusions.

Translating Basic Research Into Clinical Practice

Chest. 2008;133(6):1442-1450. doi:10.1378/chest.08-0306

Recognition of a pivotal role for eicosanoids in both normal and pathologic fibroproliferation is long overdue. These lipid mediators have the ability to regulate all cell types and nearly all pathways relevant to fibrotic lung disorders. Abnormal fibroproliferation is characterized by an excess of profibrotic leukotrienes and a deficiency of antifibrotic prostaglandins. The relevance of an eicosanoid imbalance is pertinent to diseases involving the parenchymal, airway, and vascular compartments of the lung, and is supported by studies conducted both in humans and animal models. Given the lack of effective alternatives, and the existing and emerging options for therapeutic targeting of eicosanoids, such treatments are ready for prime time.

Recent Advances in Chest Medicine

Chest. 2008;133(6):1451-1462. doi:10.1378/chest.07-2061

COPD is highly prevalent and will continue to be an increasing cause of morbidity and mortality worldwide. COPD is now viewed under a new paradigm as preventable and treatable. In addition, it has become accepted that COPD is not solely a pulmonary disease but also one with important measurable systemic consequences. Patients with COPD have to be comprehensively evaluated to determine the extent of disease so that therapy can be adequately individualized. We now know that smoking cessation, oxygen for hypoxemic patients, lung reduction surgery for selected patients with emphysema, and noninvasive ventilation during severe exacerbations have an impact on mortality. The completion of well-planned pharmacologic trials have shown the importance of decreasing resting and dynamic hyperinflation on patient-centered outcomes and the possible impact on mortality and rate of decline of lung function. In addition, therapy with pulmonary rehabilitation and lung transplantation improve patient-centered outcomes such as health-related quality of life, dyspnea, and exercise capacity. Rational use of single or multiple therapeutic modalities in combination have an impact on exacerbations and hospitalizations. This monograph presents an integrated approach to patients with COPD and updates their management incorporating the recent advances in the field. The future for patients with COPD is bright as primary and secondary prevention of smoking becomes more effective and air quality improves. In addition, current research will unravel the pathogenesis, clinical, and phenotypic manifestations of COPD, thus providing exciting therapeutic targets. Ultimately, the advent of newer and more effective therapies will lead to a decline in the contribution of this disease to poor world health.

Special Features

Chest. 2008;133(6):1463-1473. doi:10.1378/chest.07-2182

Background and aim: ARDS can occur from the following two pathogenetic pathways: a direct pulmonary injury (ARDSp); and an indirect injury (ARDSexp). The predisposing clinical factor can influence the pathogenesis and clinical outcome of ARDS. This metaanalysis was aimed at evaluating whether there is any difference in mortality between the two groups.

Methods: We searched the MEDLINE, EMBASE, and CINAHL databases for relevant studies published from 1987 to 2007, and included studies that have reported mortality in the two groups of ARDS. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess mortality in patients with ARDSp vs patients with ARDSexp and pooled the results using three different statistical models.

Results: Our search yielded 34 studies. In all, the studies involved 4,311 patients with 2,330 patients in the ARDSp group and 1,981 patients in the ARDSexp group. The OR of mortality in ARDSp group compared to the ARDSexp group was 1.11 (95% CI, 0.88 to 1.39), as determined by the random-effects model; 1.04 (95% CI, 0.92 to 1.18), as determined by the fixed-effects model; and 1.04 (95% CI, 0.92 to 1.18), as determined by the exact method, indicating that mortality is similar in the two groups. The mortality was no different whether the studies were classified as prospective (OR, 1.15; 95% CI, 0.87 to 1.51) or retrospective (OR, 1.01; 95% CI, 0.61 to 1.69); small (OR, 1.11; 95% CI, 0.77 to 1.60) or large (OR, 1.1; 95% CI, 0.82 to 1.49); or observational (OR, 1.10; 95% CI, 0.82 to 1.49) or interventional (OR, 0.97; 95% CI, 0.79 to 1.19). There was methodological and statistical heterogeneity (I2, 50.9%; 95% CI, 21.3 to 66.2%; χ2 statistic, 67.22; p = 0.0004).

Conclusions: The results of this study suggest that there is no difference in mortality between these two groups. Further studies should focus on specific etiologies within the subgroups rather than focusing on the broader division of ARDSp and ARDSexp.

Selected Report

Chest. 2008;133(6):1474-1476. doi:10.1378/chest.07-1883

A 19-year-old man presented with pneumonia, cough, and occasional dyspnea. Chest CT scan and bronchoscopy with biopsy revealed a typical carcinoid tumor obstructing the orifice of the right middle lobe, leading to lobar collapse. Preoperative surgical planning included radial endobronchial ultrasound, which confirmed that the tumor was not invasive into the bronchus intermedius. With that information, a video-assisted right middle lobectomy was performed with a wedge bronchoplasty in order to preserve the right lower lobe. The operation was performed completely thoracoscopically with three 1.2-cm ports and one 3.5-cm utility incision. With the intralobar pulmonary artery retracted, the bronchus was divided with a scalpel in wedge fashion to obtain a margin on the endobronchial tumor, and the defect was closed with absorbable suture. The patient recovered without complication and was doing well at 8-month follow-up, without evidence of recurrent disease.

Chest. 2008;133(6):1476-1478. doi:10.1378/chest.07-2354

This study describes an unusual patient with X-linked Alport syndrome (XLAS) in whom diffuse alveolar hemorrhage (DAH) developed as a complication of alemtuzumab therapy following renal transplantation. A 26-year-old man with XLAS underwent retransplantation with a cadaveric renal allograft. He received alemtuzumab therapy as a part of an immunosuppressive induction protocol, and dyspnea and hemoptysis developed. A chest CT scan showed diffuse alveolar opacities. Bronchoscopy was performed to determine the cause of hemoptysis and hypoxia. BAL showed a characteristic increasingly bloody return in the sequential aliquots. There was no growth of pathogenic bacteria or evidence of opportunistic infection. Clinical improvement occurred with the initiation of steroids, and the patient required short-term mechanical ventilation for acute respiratory failure. To our knowledge, this is the first reported case of DAH associated with use of alemtuzumab therapy, although other pulmonary toxicities have been described. The prevalence of this form of pulmonary toxicity is unclear and requires further systematic study.

Corticosteroids for Blastomycosis-Induced ARDS*: A Report of Two Patients and Review of the Literature
Chest. 2008;133(6):1478-1480. doi:10.1378/chest.07-2778

ARDS secondary to blastomycosis is associated with a high mortality rate despite appropriate antifungal therapy. Corticosteroids are of proven benefit in the treatment of severe Pneumocystis jiroveci pneumonia and are recommended for the treatment of severe pulmonary infections with Histoplasma capsulatum. However, their role in the treatment of severe pulmonary infections with Blastomyces dermatitidis has not been established. We report the cases of two previously healthy men who presented with severe ARDS secondary to blastomycosis. Refractory hypoxemia developed in both patients despite adequate antifungal coverage with amphotericin B. Dramatic improvement was seen in each patient after initiation of corticosteroids in addition to amphotericin B. Both patients survived and did well on follow-up. We suggest that treatment with corticosteroids may be of benefit in patients with blastomycosis-induced ARDS. This may be due to a decrease in the severity of the inflammatory response.

Chest. 2008;133(6):1481-1484. doi:10.1378/chest.07-1961

Bronchopulmonary fistula (BPF) is associated with high morbidity and mortality. It occurs as an uncommon but often severe complication of pneumonectomy. BPF may be treated by a range of surgical and medical techniques, including chest drain, Eloesser muscle flap, omental flap, transsternal bronchial closure, thoracoplasty, and prolonged therapy with antibiotic regimens. The use of bronchoscopy has been reported for the delivery of biological glue, coils, covered stents, and sealants. In this work, we describe a novel method of BPF closure using the Amplatzer device, which is commonly used for transcatheter closure of atrial septal defects.

Chest. 2008;133(6):1484-1488. doi:10.1378/chest.07-1891

Objectives: Three cases are presented in which patients were using opioids as required for nonmalignant pain management and significant central sleep apnea developed. Patients in the first two cases had no evidence of sleep-related breathing disorders on polysomnography until they ingested an opioid for treatment of chronic pain during the night and severe central sleep apnea developed. The patient in our third case had established obstructive sleep apnea but experienced a significant number of central events after the ingestion of an opioid analgesic, leading to worsening severity of his underlying sleep-related breathing disorder.

Conclusion: The short-term ingestion of opioid analgesics can precipitate central sleep apnea in patients with chronic pain receiving long-term opiate therapy who otherwise show no evidence of central sleep apnea and have no cardiac or neurologic disease that would predispose them to central sleep apnea.

Topics in Practice Management

Chest. 2008;133(6):1489-1494. doi:10.1378/chest.07-2150

Specialists in pulmonary and critical care medicine frequently perform invasive procedures that may require sedation or anesthesia for patient comfort. The number and complexities of interventional pulmonary procedures that can be performed in the bronchoscopy suite or critical care unit continues to expand. Procedures that formerly were done only in the operating room on inpatients are now done routinely in the office, ambulatory surgery center, or hospital outpatient department. No matter the setting, the key to successfully performing these procedures is a safe, pain-free environment for the patient. Anesthesia care and procedural sedation services share the goals of providing the patient comfort during a painful procedure and the operating physician an acceptable working environment. Historically, anesthesiologists have applied the expertise gained in managing anesthesia for major surgeries to sedation care for minor procedures. While the supply of anesthesiologists and anesthetists has shown only a modest increase, the growth in minimally invasive procedures has been explosive in recent years. To meet demand, a service, originally known as conscious sedation and now referred to as moderate sedation, has become common, in which the operating physician supervises a specially trained sedation nurse. This article will provide a clinical definition of moderate sedation and then focus on ways to properly code and bill for pulmonary procedures performed with moderate sedation.


Central Sleep Apnea*: Implications for Congestive Heart Failure
Chest. 2008;133(6):1495-1504. doi:10.1378/chest.07-0871

Congestive heart failure (HF), an exceedingly common and costly disease, is frequently seen in association with central sleep apnea (CSA), which often manifests as a periodic breathing rhythm referred to as Cheyne-Stokes respiration. CSA has historically been considered to be a marker of heart disease, since improvement in cardiac status is often associated with the attenuation of CSA. However, this mirroring of HF and CSA may suggest bidirectional importance to their relationship. In fact, observational data suggest that CSA, associated with repetitive oxyhemoglobin desaturations and surges in sympathetic neural activity, may be of pathophysiologic significance in HF outcomes. In light of the disappointing results from the first large trial assessing therapy with continuous positive airway pressure in patients with CSA and HF, further large-scale interventional trials will be needed to assess the role, if any, of CSA treatment on the outcomes of patients with HF. This review will discuss epidemiologic, pathophysiologic, diagnostic, and therapeutic considerations of CSA in the setting of HF.


Chest. 2008;133(6):1505-1507. doi:10.1378/chest.07-2566

A 36-year-old woman presented to the emergency department with acute onset of fever, chills, and lethargy. She denied headache, cough, chest, or abdominal pain. She was the owner of a dog, but denied any dog bite. Her medical history included asthma and hypothyroidism. Her medications included albuterol/ipratropium and levothyroxine. There was no history of recent travel or sick contact.

Chest. 2008;133(6):1508-1511. doi:10.1378/chest.07-2513

A 37-year-old woman presented with a sudden onset of right-sided chest pain and dyspnea the day after she underwent an abdominal hysterectomy for excessive menstrual bleeding. The pain was constant and worsened with breathing. Medical history was significant for a splenectomy following a motor vehicle accident at the age of 9 years. She had a 20–pack-year history of smoking. A pulmonary embolism was suspected. Multidetector-row spiral CT of the chest showed compression atelectasis of the basal segments of the right and left lower lobes but no pulmonary embolism. Unexpectedly, a well-circumscribed, homogeneously enhanced mediastinal nodule 15 mm in diameter was seen in the anterior superior mediastinum (Fig 1 , left, A). With analgetic treatment, she was discharged free of symptoms on the seventh postoperative day. At the following visit to the Department of Pulmonary Diseases, she denied any complaints. Physical examination and laboratory findings were unremarkable. In addition to the known mediastinal nodule (Fig 1, left, A), conventional contrast-enhanced chest CT revealed the presence of a pleural nodule 5 mm in diameter located anterolaterally in the left hemithorax (Fig 1, right. B). The patient underwent video-assisted thoracoscopic surgery. The mediastinal nodule seen on CT correlated with a reddish pedunculated nodule closely adherent to the left superior mediastinum (Fig 2 , left, A). Several other, smaller pleural-based lesions with a similar appearance were noted (Fig 2, right, B). The mediastinal nodule was resected and sent for pathologic examination (Fig 3 ). The other lesions were left intact.

Chest. 2008;133(6):1512-1516. doi:10.1378/chest.07-2263

A 56-year-old, American woman presented with shortness of breath and chest tightness for 3 weeks. She also had a dry cough for 1 week with associated fever, night sweats, and weight loss. The patient denied any other symptoms and had no history of asthma or other chronic medical illnesses. She was not taking any medications. She was working with ceramic tiles as a hobby and had not undertaken any recent travel.


Chest. 2008;133(6):1517-1523. doi:10.1378/chest.07-0212

A 40-year-old, white, nonsmoking man was admitted to the hospital in the Department of Gastroenterology with hemolytic anemia and jaundice associated with dry cough of 2 months in duration and fatigue. Pneumonia of the right lower lobe and lingular segment was diagnosed 2 months prior to hospital admission, for which the patient received a course of macrolides. There was no relevant occupational or travel history. No medications were taken on a regular basis. On hospital admission, he was afebrile and acyanotic; on examination, chest auscultation was normal and abdominal evaluation showed splenomegaly then confirmed by abdominal ultrasound.

Medical Writing Tip of the Month

All the Sourcing Not Fit To Print*: Citing Electronic Material in Your Article
Chest. 2008;133(6):1524-1526. doi:10.1378/chest.08-0234

As the Internet, and the World Wide Web in particular, become an increasing part of medical literature, it is necessary for authors to learn how to correctly cite many types of material that only exist online. Even though the conventions for citing are in flux, some standards are being developed, and authors should become familiar with the types of online material typically used as sources in medical literature. This article will discuss how to cite material that is in electronic form.


Chest. 2008;133(6):1527. doi:10.1378/chest.08-0036

I couldn’t sleep because I

Chest. 2008;133(6):1528. doi:10.1378/chest.08-0310

Waiting room,


Chest. 2008;133(6):1529-1530. doi:10.1378/chest.07-2894

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Chest. 2008;133(6):1530-1531. doi:10.1378/chest.08-0294

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Chest. 2008;133(6):1532. doi:10.1378/chest.07-3113

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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543