On June 28, 2012, a mere century after the first presidential proposal for national health insurance, the Supreme Court issued a resounding victory for President Obama and for health-care reform generally, upholding the Patient Protection and Affordable Care Act against a serious constitutional challenge. Nevertheless, the Court also struck a potential blow to future health-care reform efforts in refusing to accept the solicitor general’s argument that health care is a unique market with unique regulatory needs that justify special constitutional treatment. The failure of health-care exceptionalism in the Court’s opinion might render future reform efforts more difficult than they would have been if the solicitor general’s argument had carried the day. This commentary seeks to shed light on the Court’s hesitation to recognize the uniqueness of health insurance and health care, noting that market-based exceptionalism in constitutional law has a long, dark history that the Court was understandably loath to repeat. Although the result of Chief Justice John Roberts’ one-size-fits-all approach to constitutional analysis in this case is an odd holding that elides some genuine uniqueness of American health care, the alternative of health-care exceptionalism might have been much worse for our overall constitutional system.

Optimizing care in the ICU is an important goal. The heightened severity of illness in patients who are critically ill combined with the tremendous costs of critical care make the ICU an ideal target for improvement in outcomes and efficiency. Incorporation of evidence-based medicine into everyday practice is one method to optimize care; however, intensivists have struggled to define optimal practices because clinical trials in the ICU have yielded conflicting results. This article reviews examples where such conflicts have occurred and explores possible causes of these discrepant data as well as strategies to better use critical care clinical trials in the future.

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (EBUS-TBNA) is performed with a dedicated 22- or 21-gauge needle while suction is applied. Fine-needle sampling without suction (capillary sampling) has been studied for endoscopic ultrasound and for biopsies at various body sites and has resulted in similar diagnostic yield and fewer traumatic samples. However, the role of EBUS-guided transbronchial needle capillary sampling (EBUS-TBNCS) is still to be determined.Adults with suspicious hilar or mediastinal lymph nodes (LNs) were included in a single-blinded, prospective, randomized trial comparing EBUS-TBNA and EBUS-TBNCS. The primary end point was the concordance rate between the two techniques in terms of adequacy and diagnosis of cytologic samples. The secondary end point was the concordance rate between the two techniques in terms of quality of samples.A total of 115 patients and 192 LNs were studied. Concordance between EBUS-TBNA and EBUS-TBNCS was high, with no significant difference in adequacy (88% vs 88%, respectively [P ± .858]; concordance rate, 83.9% [95% CI, 77.9-88.8]); diagnosis (36% vs 34%, respectively [P ± .289]; concordance rate, 95.8% [95% CI, 92-92.8]); diagnosis of malignancy (28% vs 26%, respectively [P ± .125]; concordance rate, 97.9% [95% CI, 94.8-99.4]); or sample quality (concordance rate, 83.3% [95% CI, 73.3-88.3]). Concordance between EBUS-TBNA and EBUS-TBNCS was high irrespective of LN size (≤ 1 cm vs . 1 cm).Regardless of LN size, no differences in adequacy, diagnosis, or quality were found between samples obtained using EBUS-TBNA and those obtained using EBUS-TBNCS. There is no evidence of any benefit derived from the practice of applying suction to EBUS-guided biopsies.ClinicalTrials.gov; No.: NCT00886847; URL: www.clinicaltrials.gov

The lung volume reduction coil (LVR-coil), a new experimental device to achieve lung volume reduction by bronchoscopy in patients with severe emphysema, works in a manner unaffected by collateral airflow. We investigated the safety and efficacy of LVR-coil treatment in patients with heterogeneous emphysema.In this prospective cohort pilot study, patients were treated bronchoscopically with Nitinol LVR-coils under fluoroscopic guidance in either one procedure or two sequential procedures. Follow-up tests included the St. George Respiratory Questionnaire (SGRQ), pulmonary function testing, and the 6-min walk test (6MWT).Twenty-eight LVR-coil procedures were performed in 16 patients (baseline FEV₁, 28% [± 7.6%] predicted). Four patients were treated in one lung, and 12 patients were treated in both lungs. A median of 10 (5-12) coils was placed per lung in 36.5 (20-60) min. Adverse events (AEs) rated as possibly related to either the device or the procedure < 30 days after treatment were pneumothorax (n ± 1), pneumonia (n ± 2), COPD exacerbation (n ± 6), chest pain (n ± 4), and mild (<, 5 mL) hemoptysis (n ± 21). From 30 days to 6 months, the AEs that occurred were pneumonia (n ± 3) and COPD exacerbation (n ± 14). All events resolved with standard care. Six months after LVR-coil treatment, there were significant improvements in SGRQ (×14.9 points [± 12.1 points, with 11 patients improving by . 4 points]), FEV₁ (−14.9% ± 17.0%), FVC (−13.4% ± 12.9%), residual volume (×11.4% ± 9.0%), and 6MWT (−84.4 ± 73.4 m), all P < .005.LVR-coil treatment is a promising technique for the treatment of patients with severe heterogeneous emphysema. The treatment is technically feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life, with an acceptable safety profile.ClinicalTrials.gov; No.:NCT01220908; URL: www.clinicaltrials.gov

No data on long-term outcomes of survivors of 2009 influenza A(H1N1) (A[H1N1])-associated ARDS are available. The objective of this study was to compare the 1-year outcomes of survivors of A(H1N1)-associated ARDS, according to use or no use of extracorporeal lung assist (ECLA), using its need as an ARDS severity surrogate.Survivors of ARDS (12 with ECLA use vs 25 without, corresponding to 75% and 54% of the eligible patients for each group, respectively) selected from the Réseau Européen de Ventilation Artificielle (REVA) registry had previously been healthy, with only pregnancy and/or moderate obesity (BMI ≤ 35 kg/m²) as known risk factors for A(H1N1) infection. Lung function and morphology, health-related quality of life (HRQoL), and psychologic impairment were evaluated.At 1 year post-ICU discharge for the ECLA and no-ECLA groups, respectively, 50% and 40% reported significant exertion dyspnea, 83% and 64% had returned to work, and 75% and 64% had decreased diffusion capacity across the blood-gas barrier, despite their near-normal and similar lung function test results. For both groups, exercise test results showed diminished but comparable exercise capacities, with similar alveolar-arterial oxygen gradients at peak exercise, and CT scans showed minor abnormal findings. HRQoL assessed by the 36-Item Short-Form Health Survey was poorer for both groups than for a sex- and age-matched general population group, but without between-group differences. ECLA and no-ECLA group patients, respectively, had symptoms of anxiety (50% and 56%) and depression (28% and 28%) and were at risk for posttraumatic stress disorder (41% and 44%).One year post-ICU discharge, a majority of survivors of A(H1N1)-associated ARDS had minor lung disabilities with diminished diffusion capacities across the blood-gas barrier, and most had psychologic impairment and poorer HRQoL than a sex- and age-matched general population group. ECLA and no-ECLA group patients had comparable outcomes.ClinicalTrials.gov; No.: NCT01271842; URL: www.clinicaltrials.gov

Vasopressin is known to be an effective vasopressor in the treatment of septic shock, but uncertainty remains about its effect on other hemodynamic parameters.We examined the cardiopulmonary effects of vasopressin compared with norepinephrine in 779 adult patients with septic shock recruited to the Vasopressin and Septic Shock Trial. More detailed cardiac output data were analyzed for a subset of 241 patients managed with a pulmonary artery catheter, and data were collected for the first 96 h after randomization. We compared the effects of vasopressin vs norepinephrine in all patients and according to severity of shock (< 15 or ≥ 15 νg/min of norepinephrine) and cardiac output at baseline.Equal BPs were maintained in both treatment groups, with a significant reduction in norepinephrine requirements in the patients treated with vasopressin. The major hemodynamic difference between the two groups was a significant reduction in heart rate in the patients treated with vasopressin (P <.0001), and this was most pronounced in the less severe shock stratum (treatment ÷ shock stratum interaction, P =.03). There were no other major cardiopulmonary differences between treatment groups, including no difference in cardiac index or stroke volume index between patients treated with vasopressin and those treated with norepinephrine. There was significantly greater use of inotropic drugs in the vasopressin group than in the norepinephrine group.Vasopressin treatment in septic shock is associated with a significant reduction in heart rate but no change in cardiac output or other measures of perfusion.ISRCTN Register; No.:ISRCTN94845869; URL: www.isrctn.org

Patient safety remains a national priority, but the role of disease-specific characteristics in safety is not well characterized.We identified potentially preventable medical injuries using patient safety indicators (PSIs) and annual data from the Nationwide Inpatient Sample between 2003 and 2007. We compared the rate of selected PSIs among patients hospitalized with and without sepsis. Among patients with sepsis, we also compared PSI rates across severity strata. Using multivariable case-control matching and regression analyses, we estimated the excess adverse outcomes associated with PSI events in patients with sepsis.Patients hospitalized with sepsis accounted for 2% to 4% of hospital discharges; however, they accounted for 9% to 26% of all potential medical injuries. PSI rates varied considerably; among patients hospitalized for sepsis, they were lowest for accidental puncture or laceration and highest for postoperative respiratory failure. Nearly all PSI rates were higher among patients with sepsis compared with patients without sepsis. Among those with sepsis, most PSI rates increased as sepsis severity increased. Compared with matched sepsis control subjects, increased length of stay and hospital charges were associated with PSI events in sepsis cases. However, only decubitus ulcer, iatrogenic pneumothorax, and postoperative metabolic and physiologic derangement or respiratory failure were associated with excess mortality.Patients hospitalized for sepsis, compared with the general hospital population, were at a substantially increased risk of potential medical injury; their risk rose as disease severity increased. Future patient safety efforts may benefit from focusing on medically vulnerable populations.

Cough is a significant symptom in patients with scleroderma interstitial lung disease (SSc-ILD), affecting 73% of the 158 patients enrolled in the Scleroderma Lung Study (SLS), a multicenter randomized trial of oral cyclophosphamide (CYC) vs placebo (PLA) in patients with active interstitial lung disease.We examined the correlation of cough frequency and severity and phlegm production at baseline in 156 SLS participants with other baseline variables representing SSc-ILD disease activity and the cough response to 1 year of treatment with CYC vs PLA.Patients with cough at baseline had significantly lower diffusing capacity of the lung for carbon monoxide, dyspnea, the quality-of-life physical component summary, and the maximal fibrosis score on high-resolution CT imaging compared with those without cough at baseline. Cough severity and frequency correlated with FVC % predicted. After 12 months of treatment, cough frequency decreased in the CYC group compared with the PLA group and was significantly different from the PLA group at 18 months (6 months after discontinuation of CYC). However, the decreases in cough frequency did not correlate with the changes in FVC or diffusing capacity of the lung for carbon monoxide observed in the CYC group. Treatment-related improvements in cough frequency, as well as in FVC, were no longer apparent 12 months after discontinuation of CYC.Cough is a common symptom in SSc-ILD and correlates with the extent of fibrosis. Cough frequency decreases significantly in response to treatment with CYC but returns to baseline 1 year after withdrawal of treatment. Cough may be a symptom of ongoing fibrosis and an independent variable in assessing therapeutic response to CYC.ClinicalTrials.gov; No.: NCT000004563; URL: www.clinicaltrials.gov

Sleep complaints are common among patients with traumatic brain injury. Evaluation of this population is confounded by polypharmacy and comorbid disease, with few studies addressing combat-related injuries. The aim of this study was to assess the prevalence of sleep disorders among soldiers who sustained combat-related traumatic brain injury.The study design was a retrospective review of soldiers returning from combat with mild to moderate traumatic brain injury. All underwent comprehensive sleep evaluations. We determined the prevalence of sleep complaints and disorders in this population and assessed demographics, mechanism of injury, medication use, comorbid psychiatric disease, and polysomnographic findings to identify variables that correlated with the development of specific sleep disorders.Of 116 consecutive patients, 96.6% were men (mean age, 31.1 ± 9.8 years; mean BMI, 27.8 ± 4.1 kg/m²), and 29.5% and 70.5% sustained blunt and blast injuries, respectively. Nearly all (97.4%) reported sleep complaints. Hypersomnia and sleep fragmentation were reported in 85.2% and 54.3%, respectively. Obstructive sleep apnea syndrome (OSAS) was found in 34.5%, and 55.2% had insomnia. Patients with blast injuries developed more anxiety (50.6% vs 20.0%, P ± .002) and insomnia (63% vs 40%, P ± .02), whereas patients with blunt trauma had significantly more OSAS (54.3% vs 25.9%, P ± .003). In multivariate analysis, blunt trauma was a significant predictor of OSAS (OR, 3.09; 95% CI, 1.02-9.38; P ± .047).Sleep disruption is common following traumatic brain injury, and the majority of patients develop a chronic sleep disorder. It appears that sleep disturbances may be influenced by the mechanism of injury in those with combat-related traumatic brain injury, with blunt injury potentially predicting the development of OSAS.

Sleepiness is one of the most burdensome symptoms of sleep-disordered breathing (SDB). While caffeine is frequently used to avert sleepiness, the association between SDB and caffeine use has not been thoroughly explored. The current study examined whether SDB is associated with caffeine consumption and if factors such as sex, age, and daytime sleepiness explain or modify the association.Data from the Sleep Heart Health Study, a community-based study on the consequences of SDB, were used to characterize the association between SDB and caffeine intake. SDB was assessed with full-montage polysomnography. Caffeine use was quantified as the number of cans of soda or the cups of coffee or tea consumed daily. The Epworth Sleepiness Scale was used to assess daytime sleepiness. Multivariable negative binomial regression models were used to characterize the independent association between SDB and caffeine use.Caffeinated soda, but not tea or coffee, intake was independently associated with SDB severity. Compared with participants without SDB, the relative ratios for caffeinated soda consumption in women with mild, moderate, and severe SDB were 1.20 (CI, 1.03-1.41), 1.46 (CI, 1.14-1.87), and 1.73 (CI, 1.23-2.42), respectively. For men, an association was only noted with severe SDB and caffeinated soda use. Age did not modify the SDB-caffeine association, and sleepiness could not explain the observed associations.SDB is independently associated with caffeinated soda use in the general community. Identifying excessive caffeine used in SDB has potential significance given the cardiovascular effects of caffeine and untreated SDB.

Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. Stress imposed on the myocardium by repeated severe hypoxemia and/or BP surges during sleep may result in subclinical myocardial injury. A high-sensitivity cardiac troponin T (hs-cTnT) assay has been developed. We hypothesized that the severity of OSA, as assessed by the apnea-hypopnea index (AHI), is associated with circulating levels of hs-cTnT in the general population.Five hundred five subjects drawn from the general population (age range, 30-65 years; 45% women) underwent in-hospital polysomnography and had morning blood samples drawn. Oversampling of subjects at high risk of OSA was performed.Overall, hs-cTnT was detectable (≥ 3 ng/L) in 216 subjects (42.8%). After categorizing subjects according to AHI cutoffs that correspond to no, mild to moderate, and severe OSA, the proportion of subjects with detectable hs-cTnT levels increased with increasing severity of OSA (P for trend < .001). Multivariate logistic regression with detectable hs-cTnT as the dependent variable was used to further assess the association between OSA and troponin T. After adjustment for significant univariate predictors of detectable hs-cTnT, the association between AHI and hs-cTnT was no longer statistically significant.The prevalence of detectable hs-cTnT increases in proportion to OSA severity, but this association is likely to be caused by a clustering of cardiovascular risk factors among subjects with OSA.

Few studies have examined common childhood infections and adult asthma. We examined associations between childhood infectious diseases, childhood pneumonia, and current, persisting, and incident asthma to middle age.We analyzed data from the Tasmanian Longitudinal Health Study (TAHS). A history of pneumonia was ascertained from their parents when the TAHS participants were 7 years old. Measles, rubella, mumps, chickenpox, diphtheria, and pertussis were identified from school medical records. Associations with current, persisting, or incident asthma were examined using regression techniques.Greater infectious diseases load was negatively associated with persisting asthma at all ages. Individually, pertussis (adjusted OR [aOR], 0.53; 95% CI, 0.28-1.00) was negatively associated with asthma persisting to age 13 years, chickenpox (aOR, 0.58; 95% CI, 0.38-0.88) was negatively associated with asthma persisting to age 32 years, and rubella was negatively associated with asthma persisting to ages 32 (aOR, 0.61; 95% CI, 0.31-0.96) and 44 years (aOR 0.53; 95% CI, 0.35-0.82). Pertussis was associated with preadolescent incident asthma (adjusted hazard ratio [aHR], 1.80; 95% CI, 1.10-2.96), whereas measles was associated with adolescent incident asthma (aHR, 1.66; 1.06-2.56). Childhood pneumonia was associated with current asthma at ages 7 (aOR, 3.12; 95% CI, 2.61-3.75) and 13 years (aOR, 1.32; 95% CI, 1.00-1.75), an association stronger in those without than those with eczema (aOR, 3.46; 95% CI, 2.83-4.24 vs aOR, 2.08; 95% CI, 1.38-3.12).Overall, childhood infectious diseases protected against asthma persisting in later life, but pertussis and measles were associated with new-onset asthma after childhood. Measles and pertussis immunization might lead to a reduction in incident asthma in later life.

It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV₁.Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans.The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m². Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m² (P = .01), independent of airflow obstruction (FEV₁), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV₁ or quantitative CT scan measures of airway dimension.More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV₁. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation.

MicroRNAs (miRNAs) are small noncoding RNAs that silence target gene expression posttranscriptionally, and their impact on gene expression has been reported in various diseases. It has been reported that the expression of the hypoxia-inducible factor-1α (HIF-1α) is reduced and that of p53 is increased in lungs from patients with COPD. However, the role of miRNAs associated with these genes in lungs from patients with COPD is unknown.Lung tissue samples from 55 patients were included in this study. Total RNA, miRNA, and protein were extracted from lung tissues and used for reverse transcriptase polymerase chain reaction and Western blot analysis. Cell culture experiments were performed using cultured human pulmonary microvascular endothelial cells (HPMVECs).miR-34a and miR-199a-5p expressions were increased, and the phosphorylation of AKT was decreased in the lung tissue samples of patients with COPD. The miR-199a-5p expression was correlated with HIF-1α protein expression in the lungs of patients with COPD. Transfection of HPMVECs with the miR-199a-5p precursor gene decreased HIF-1α protein expression, and transfection with the miR-34a precursor gene increased miR-199a-5p expression.These data suggest that miR-34a and miR-199a-5p contribute to the pathogenesis of COPD, and these miRNAs may also affect the HIF-1α-dependent lung structure maintenance program.

The implementation of workplace smoking bans has contributed to a significant reduction in the incidence of acute coronary syndrome admissions, but their influence on adult acute pulmonary disease admissions is unclear. We sought to assess the impact of a national smoking ban on nationwide admissions of individuals of working age with acute pulmonary illness.Data relating to emergency hospital admissions of subjects aged 20 to 70 years preceding and succeeding the implementation of the Irish smoking ban were obtained from a central registry. Population, weather, pollution, and influenza data were obtained from the relevant authorities. Poisson regression analysis was used to assess adjusted risk of emergency hospital admission following implementation of the smoking ban.Overall admissions with pulmonary illness decreased from 439 per 100,000 population per annum to 396 per 100,000 population per annum following the ban (unadjusted relative risk [RR], 0.91; 95% CI, 0.83-0.99; P = .048). This persisted following adjustment for confounding factors (adjusted RR, 0.85; 95% CI, 0.72-0.99; P = .04) and was most marked among younger age groups and in admissions due to asthma (adjusted RR, 0.60; 95% CI, 0.39-0.91; P = .016). Admissions with acute coronary syndromes (adjusted RR, 0.82; 95% CI, 0.70-0.97; P = .02), but not stroke (adjusted RR, 0.93; 95% CI, 0.73-1.20; P = .60), were also reduced.The implementation of a nationwide workplace smoking ban is associated with a decline in admissions with acute pulmonary disease among specific age groups and an overall reduction in asthma admissions. This may result from reduced exposure of vulnerable individuals to environmental tobacco smoke, emphasizing the potential benefit of legislation reducing second-hand smoke exposure.

CASP7 plays a crucial role in cancer development and chemotherapy efficacy. We, therefore, explored whether single nucleotide polymorphisms (SNPs) of the CASP7 gene can modulate outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy.We systematically genotyped 17 SNPs of CASP7 first in a discovery set of 279 patients with advanced NSCLC treated with platinum-based chemotherapy and then replicated the results in an independent set of 384 patients, in whom we evaluated associations with overall survival (OS) and progress-free survival (PFS) by Kaplan-Meier analysis and Cox hazards regression analysis.In both discovery and validation sets as well as in the pooled analysis, heterozygotes of CASP7 rs2227310 and rs4353229 as well as rs12415607 variant allele were strongly associated with a better OS of NSCLC (in the pooled sample: adjusted hazard ratio [HR], 0.73; 95% CI = 0.59-0.90; P = .003; HR, 0.72; 95% CI = 0.59-0.89; P = .002; and HR, 0.76; 95% CI = 0.62-0.94; P = .009; respectively). In stratified analyses of the pooled data set, treated with paclitaxel, individuals carrying variant allele of rs2227310, rs4353229, and rs12415607 had significantly improved OS (HR, 0.60; 95% CI = 0.41-0.87; P = .008; HR, 0.58; 95% CI = 0.39-0.84; P = .004; and HR, 0.61; 95% CI = 0.42-0.89; P = .010; respectively).This study provides evidence that genetic variations of CASP7 may modulate OS and PFS of patients with advanced NSCLC treated with platinum-based chemotherapy.

Pulmonary embolism is a common, often fatal condition that requires timely recognition and rapid institution of therapy. Previous studies have documented worse outcomes for weekend admissions for a variety of time-sensitive medical conditions. This phenomenon has not been clearly demonstrated for pulmonary embolism.We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 2000 to 2008 to identify people with a principal discharge diagnosis of pulmonary embolism. We classified admissions as weekend if they occurred between midnight Friday and midnight Sunday. We compared all-cause in-hospital mortality between weekend and weekday admissions and investigated the timing of inferior vena cava (IVC) filter placement and thrombolytic infusion as potential explanations for differences in mortality.Unadjusted mortality was higher for weekend admissions than weekday admissions (OR, 1.19; 95% CI, 1.13-1.24). This increase in mortality remained statistically significant after controlling for potential confounding variables (OR, 1.17; 95% CI, 1.11-1.22). Among patients who received an IVC filter, a larger proportion of those admitted on a weekday than on the weekend received it on their first hospital day (38% vs 29%, P < .001). The timing of thrombolytic therapy did not differ between weekday and weekend admissions.Weekend admissions for pulmonary embolism were associated with higher mortality than weekday admissions. Our finding that IVC filter placement occurred later in the hospital course for patients admitted on weekends with pulmonary embolism suggests differences in the timeliness of diagnosis and treatment between weekday and weekend admissions. Regardless of cause, physicians should be aware that weekend admissions for pulmonary embolism have a 20% increased risk of death and warrant closer attention than provided during the week.

The diagnostic workup of pulmonary embolism (PE) may take several hours. The usefulness of anticoagulant treatment while awaiting the results of diagnostic tests has not been assessed. The objective of this study was to compare the risks and benefits of bid low-molecular-weight heparin vs no treatment in patients with suspected PE.We developed a decision tree with the following outcomes: mortality related to untreated and treated PE, mortality due to major hemorrhage, and intracranial bleeding. The timeframe extended from the suspicion of PE to its confirmation or exclusion. Most probabilities were derived from data from the Computerized Registry of Patients with VTE (RIETE). We estimated the incidence of bleeding by categories of clinical prediction rules of PE from a recent diagnostic management study of PE. Uncertainty was assessed through one-way and probabilistic sensitivity analyses.The model favored preemptive anticoagulation if the diagnostic delay was . 6.3 h, . 2.3 h, and . 0.3 h (Revised Geneva low, intermediate, and high probability) and . 8.1 h and . 1.7 h (Wells unlikely and likely). With a diagnostic delay of 6 h, the absolute mortality reduction with anticoagulation was 0%, 0.02%, and 0.1% for low, intermediate, and high clinical probability, respectively. In one-way sensitivity analyses, the mortality of untreated PE was the most critical variable. Probabilistic analyses reinforced the superiority of anticoagulation in intermediate- and high-probability patients and suggested that low-probability patients might not benefit from treatment after diagnostic delays of < 6 to 8 h.Our model suggests that patients with intermediate and high/likely probabilities of PE benefit from preemptive anticoagulation. With a low probability, the decision to treat may rely on the expected diagnostic delay.

Health-related quality-of-life (HRQL) measures have been correlated with lung function in patients with COPD and interstitial lung disease (ILD). However, different pathophysiologic mechanisms may influence how these distinct diseases affect HRQL, resulting in differing HRQL by pulmonary diagnosis among patients with similar severity of ventilatory impairment.The National Heart, Lung, and Blood Institute Lung Tissue Research Consortium provided data on well-characterized participants with COPD (n = 576) and ILD (n = 405) at four clinical sites. Using multiple linear regression, we examined the effects of FEV₁ (% predicted) and diagnosis (ILD vs COPD) on HRQL scores, including total St. George Respiratory Questionnaire (SGRQ) scores and Short Form-12 (SF-12) physical component summary (PCS) and mental component summary (MCS) scores.Participants with ILD had, on average, higher SGRQ scores (15.33 points; 95% CI, 12.46-18.19; P <.001) and lower SF-12 PCS scores (×4.73 points; 95% CI, ×6.31 to ×3.14; P <.001) compared with patients with COPD with similar FEV₁ % predicted values, indicating worse HRQL. The specific diagnosis also modified the effect of FEV₁ on the total SGRQ score (P = .003) and the SF-12 PCS score (P = .03). There was no relationship between lung function and SF-12 MCS scores.HRQL scores were worse for patients with ILD compared with patients with COPD with similar degrees of ventilatory impairment. Differences in dyspnea mechanism or in the rate of disease progression may account for these differences in HRQL.

Nutrition is an important component of clinical care for patients with cystic fibrosis. We aimed to test the hypothesis that increased BMI, height, and level of creatinine as a biomarker for lean muscle mass are associated with lower mortality and whether differences in these measures may contribute toward sex differences in survival in cystic fibrosis.Using a cohort study design, we analyzed data from the UK Cystic Fibrosis Registry for patients who attended an annual assessment visit in 2007 and were followed-up until July 2009.Of 1,517 individuals, 62 died during the follow-up period. The odds of death were higher among patients in the lowest quintile of serum creatinine compared with the rest of the study population (OR, 3.28; 95% CI, 1.79-5.98). Increased height and higher BMI were also associated with lower risk of death. The higher mortality in female patients (OR, 1.48; 95% CI, 0.93-2.34) was reversed by adjustment using the absolute values for height, BMI, and serum creatinine level (adjusted OR, 0.44; 95% CI, 0.21-0.90) but not by the use of sex-specific values for these exposure variables.Lower muscle mass, shorter stature, and a low BMI are associated with increased mortality in cystic fibrosis. These measures of body habitus may contribute to the sex-specific survival differences in individuals with cystic fibrosis.

Ivacaftor (VX-770) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that was approved in the United States for the treatment of cystic fibrosis (CF) in patients ≥ 6 years of age who have a G551D mutation; however, the most prevalent disease-causing CFTR mutation, F508del, causes a different functional defect. The objectives of this study were to evaluate the safety of ivacaftor in a larger population and for a longer time period than tested previously and to assess the efficacy of ivacaftor in subjects with CF who are homozygous for F508del-CFTR.This was a phase 2 study with a 16-week randomized (4:1), double-blind, placebo-controlled period (part A) and an open-label extension (part B) for subjects who met prespecified criteria.Part A: The safety profile of ivacaftor was comparable to that of the placebo. The overall adverse event frequency was similar in the ivacaftor (87.5%) and placebo (89.3%) groups through 16 weeks. The difference in the change of FEV₁ % predicted from baseline through week 16 (primary end point) between the ivacaftor and placebo groups was 1.7% (P = .15). Sweat chloride, a biomarker of CFTR activity, showed a small reduction in the ivacaftor vs placebo groups of −2.9 mmol/L (P = .04) from baseline through week 16. Part B: No new safety signals were identified. The changes in FEV₁ or sweat chloride in part A were not sustained with ivacaftor treatment from week 16 to week 40.These results expand the safety information for ivacaftor and support its continued evaluation. Lack of a clinical effect suggests that a CFTR potentiator alone is not an effective therapeutic approach for patients who have CF and are homozygous for F508del-CFTR.ClinicalTrials.gov; No.: NCT00953706; URL: www.clinicaltrials.gov.

The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era.We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV₁ by 20% [PC₂₀]), lung volumes, diffusion, and cardiopulmonary exercise tolerance.Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV₁ % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC₂₀ was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC₂₀ was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01).Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity.From the Pulmonary Institute (Drs Kaplan, Bar-Yishay, Prais, Mei-Zahav, Mussaffi, Steuer, Hananya, Blau and Mss Matyashuk and Gabarra) and Department of Neonatal Intensive Care (Drs Klinger and Sirota), Schneider Children’s Medical Center of Israel, Petah Tikva; and Sackler Faculty of Medicine (Drs Prais, Klinger, Mei-Zahav, Mussaffi, Sirota, and Blau), Tel Aviv University, Tel Aviv, Israel.

Correspondence to: Hannah Blau, MBBS, Pulmonary Institute, Schneider Children’s Medical Center of Israel, 14 Kaplan St, Petah Tikva, 49202, Israel; e-mail: hblau@post.tau.ac.il

Author contributions: Dr Blau had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Kaplan: contributed to the study conception and design, patient recruitment, performance of lung function tests, analysis and interpretation of data, and writing of the manuscript.

Dr Bar-Yishay: contributed to the performance of lung function tests, analysis and interpretation of data, and revision of the manuscript.

Dr Prais: contributed to the performance of lung function tests, analysis and interpretation of data, and revision of the manuscript.

Dr Klinger: contributed to the patient recruitment, data collection, and revision of the manuscript.

Dr Mei-Zahav: contributed to the interpretation of data and revision of the manuscript.

Dr Mussaffi: contributed to the interpretation of data and revision of the manuscript.

Dr Steuer: contributed to the interpretation of data and revision of the manuscript.

Dr Hananya: contributed to the interpretation of data and revision of the manuscript.

Ms Matyashuk: contributed to the performance of the pulmonary function tests, to collate data within the study database, and the writing of the manuscript.

Ms Gabarra: contributed to the performance of the pulmonary function tests, to collate data within the study database, and the writing of the manuscript.

Dr Sirota: contributed to the patient recruitment, data collection, and revision of the manuscript.

Dr Blau: contributed to the study conception and design, patient recruitment, analysis and interpretation of data, and writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Prais has received pharmaceutical grant money from Abbott Laboratories and has done academic lectures to medical staff, receiving honoraria from Merck Sharp & Dohme Corp. Drs Kaplan, Bar-Yishay, Klinger, Mei-Zahav, Mussaffi, Steuer, Hananya, Sirota, and Blau and Mss Matyashuk and Gabarra have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The Israel Association of Clinical Pediatrics provided unconditional financial support. The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: This study was performed at the Schneider Children’s Medical Center of Israel. We are grateful to Pearl Lilos, BSc, for her patience and dedication in statistical analysis of this study. We thank all the subjects for participating in a long day of lung function testing.

The initial enthusiasm for the advent of a potentially nonnephrotoxic immunosuppressant has been muted by data unmasking nephrotoxicity of mammalian target of rapamycin inhibitors, including renal podocyte injury resulting in proteinuria. Adverse reactions, including anemia, thrombocytopenia, hyperlipidemia, and especially diabetogenesis, have limited its use to niche indications such as prevention or amelioration of malignancy in organ transplant. The class seems to be best used to address malignancy in organ allograft recipients and as a first-line therapy in lymphangioleiomyomatosis.

Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, comprehensive intervention that can be integrated into the management of individuals with chronic lung disease. It aims to reduce symptoms, optimize function, increase participation in daily life, and reduce health-care resource utilization. In this review, we summarize the new developments in PR over the past 5 years. Issues related to patient assessment include a comparison of cycle- and walking-based measures of exercise capacity, the emergence of multidimensional indices, the refinement of the minimal clinically important difference, and the importance of assessing physical activity. Issues related to exercise training focus on strategies to optimize the training load. We also comment on the acquisition of self-management skills, balance training, optimizing access, and maintaining gains following completion of PR.

In the past 3 decades, the total number of CT scans performed has grown exponentially. In 2007, > 70 million CT scans were performed in the United States. CT scan studies of the chest comprise a large portion of the CT scans performed today because the technology has transformed the management of common chest diseases, including pulmonary embolism and coronary artery disease. As the number of studies performed yearly increases, a growing fraction of the population is exposed to low-dose ionizing radiation from CT scan. Data extrapolated from atomic bomb survivors and other populations exposed to low-dose ionizing radiation suggest that CT scan-associated radiation may increase an individual’s lifetime risk of developing cancer. This finding, however, is not incontrovertible. Because this topic has recently attracted the attention of both the scientific community and the general public, it has become increasingly important for physicians to understand the cancer risk associated with CT scan and be capable of engaging in productive dialogue with patients. This article reviews the current literature on the public health debate surrounding CT scan and cancer risk, quantifies radiation doses associated with specific studies, and describes efforts to reduce population-wide CT scan-associated radiation exposure. CT scan examinations of the chest, including CT scan pulmonary and coronary angiography, high-resolution CT scan, low-dose lung cancer screening, and triple rule-out CT scan, are specifically considered.

About one-third of the world population has latent TB infection (LTBI), the majority of which is distributed in 22 high-burden countries. Early diagnosis and treatment of active TB remains the top priority in resource-poor countries with high TB prevalence. Notwithstanding, because LTBI contributes significantly to the pool of active TB cases later on, its diagnosis and treatment is essential, especially in high-risk groups. The lack of a gold standard and several limitations of currently available tools, namely the tuberculin skin test and interferon-γ release assays, are major constraints for LTBI diagnosis. In areas with high TB prevalence, interferon-γ release assays have not shown superiority over the conventional tuberculin skin test and are yet to be systematically studied. Decisions regarding LTBI treatment with isoniazid preventive therapy should be made, keeping in mind the high prevalence of isoniazid resistance in these settings. Although efforts to shorten the LTBI treatment duration are encouraging, most trials have focused on adherence and toxicity. Future trials on short-duration regimens in high-burden settings should address drug efficacy issues as well. LTBI management, therefore, should comprise a targeted screening approach and individualization of LTBI treatment protocols. In addition, efforts should focus on airborne infection control measures in high-burden countries. A high prevalence of drug-resistant TB, the HIV epidemic, and delays in the diagnosis of active TB cases are other major concerns in areas of high TB prevalence. There is ample space for further research in these countries, whose outcomes may strengthen future national guidelines.

The term “children’s interstitial lung disease” (chILD) refers to a heterogeneous group of rare and diffuse lung diseases associated with significant morbidity and mortality. These disorders include neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis, surfactant dysfunction mutations, and alveolar capillary dysplasia with misalignment of pulmonary veins. Diagnosis can be challenging, which may lead to a delay in recognition and treatment of these disorders. Recently, International Classifications of Diseases, Ninth Revision codes have been added for several of the chILD disorders. The purpose of this article is to give an overview of the chILD disorders and appropriate diagnostic coding.

We describe a 29-year-old woman who presented with chronic pleuropericarditis complicated by lung entrapment and constrictive pericarditis. Pleural biopsy performed during the decortication procedure revealed fibrinous pleuritis with lymphoplasmacytic inflammation including IgG4-positive plasma cells. The patient responded favorably to corticosteroid therapy with resolution of pleural effusion and constrictive physiology. To our knowledge, this is the first reported case of IgG4-related systemic disease manifesting as lung entrapment and constrictive pericarditis.

Mycobacterial spindle cell pseudotumor (MSP) is a rare benign lesion characterized by local proliferation of spindle-shaped histiocytes containing acid-fast mycobacteria. Most reported cases of MSP occur in the lymph nodes, skin, spleen, and brain in patients who are immunocompromised, particularly following solid organ transplant and in those with AIDS. This is a case report of a patient with AIDS who presented with cough, generalized weakness, and fatigue, who was found to have multilobar lung masses that were MSP, which to our knowledge has not yet been reported in the literature.

Obesity prevalence continues to increase globally, with figures exceeding 30% of some populations. Patients who are obese experience alterations in baseline pulmonary mechanics, including airflow obstruction, decreased lung volumes, and impaired gas exchange. These physiologic changes have implications in many diseases, including ARDS. The unique physiology of patients who are obese affects the presentation and pathophysiology of ARDS, and patients who are obese who have respiratory failure present specific management challenges. Although more study is forthcoming, ventilator strategies that focus on transpulmonary pressure as a measure of lung stress show promise in pilot studies. Given the increasing prevalence of obesity and the variable effects of obesity on respiratory mechanics and ARDS pathophysiology, we recommend an individualized approach to the management of the obese patient with ARDS.