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BACKGROUND - The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository.
METHODS/DESIGN - Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, peripheral blood samples, baseline CT, and medical and demographic data were collected from each subject.
DISCUSSION - Over a two-year span (2010-2012), 403 subjects were enrolled at 12 sites. At baseline 384 subjects remained in study and mean age and smoking history were 62.9 years and 50.4 pack-years respectively, with 34% current smokers. Obstructive lung disease (FEV1/FVC <0.7) was present in 157 (54%). No severe adverse events were associated with bronchoscopic brushing. An NBEC and matched peripheral blood bio-specimen repository was established. The demographic composition of the enrolled group is representative of the population for which the LCRT is intended. Specifically, based on baseline population characteristics we expect lung cancer incidence in this cohort to be representative of the population eligible for low-dose Computed Tomography (LDCT) lung cancer screening. Collection of NBEC by bronchial brush biopsy/bronchoscopy was safe and well-tolerated in this population. These findings support the feasibility of testing LCRT clinical utility in this prospective study. If validated, the LCRT has the potential to significantly narrow the population of individuals requiring annual low-dose helical CT screening for early detection of lung cancer and delay the onset of screening for individuals with results indicating low lung cancer risk. For these individuals, the small risk incurred by undergoing once in a lifetime bronchoscopic sample collection for LCRT may be offset by a reduction in their CT-related risks. The LCRT biospecimen repository will enable additional studies of genetic basis for COPD and/or lung cancer risk.
TRIAL REGISTRATION - The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010.
RATIONALE - The association between pulmonary function and morbidity in children with sickle cell disease (SCD) has not been previously evaluated. Our objective was to study the relationship between abnormalities in pulmonary function and morbidity as represented by the rate of hospitalizations for pain or acute chest syndrome (ACS) in children with SCD.
METHODS - Results of pulmonary function tests obtained for clinical indications in children ages 6-18 years were classified as lower airway obstruction (forced expiratory volume in 1 sec/forced volume capacity <95% confidence interval adjusted for age, gender, race, and height), restriction (total lung capacity <80% predicted adjusted for gender, age, race, and height), and normal lung function. Incidence rates of pain or ACS were compared between children with lower airway obstruction or restriction and children with normal lung function.
RESULTS - A total of 102 children, mean age at evaluation 12.0 years with follow-up of 3.8 years, were included. Children with lower airway obstruction had twice the rate of morbidity compared to children with normal lung function (2.5 vs. 1.2 hospitalizations for pain or ACS per patient-year, P = 0.003) (Risk ratio: 2.0; 95% CI: 1.3-3.3). Children with restriction did not have different rates of future morbidity compared to children with normal lung function (1.4 vs. 1.2 hospitalizations for pain or ACS per patient-year, P = 0.68) (Rate ratio: 1.1; 95% CI: 0.6-2.1).
CONCLUSIONS - We conclude that children with SCD who have lower airway obstruction should have increased surveillance for future morbidity.
CONTEXT - Many are calling for patients with advanced chronic obstructive pulmonary disease (COPD) to receive hospice care, but the traditional hospice model may be insufficient.
OBJECTIVE - To compare the course of illness and patterns of care for patients with non-small cell lung cancer and severe COPD.
DESIGN - Prospective cohort study of seriously ill, hospitalized adults.
SETTING - Five teaching hospitals in the United States.
PATIENTS - Patients with Stage III or IV non-small cell lung cancer (n = 939) or acute exacerbation of severe COPD (n = 1008).
MAIN OUTCOME MEASURES - Patients' preferences for pattern of care and for ventilator use; symptoms; life-sustaining interventions; and survival prognoses.
RESULTS - Sixty percent in each group wanted comfort-focused care; 81% with lung cancer and 78% with COPD were extremely unwilling to have mechanical ventilation indefinitely. Severe dyspnea occurred in 32% of patients with lung cancer and 56% of patients with COPD and severe pain in 28 % of patients with lung cancer and 21% of patients with COPD. Patients with COPD who died during index hospitalization were more likely than patients with lung cancer to receive mechanical ventilation (70.4% vs 19.8%), tube feeding (38.7% vs 18.5%), and cardiopulmonary resuscitation (25.2% vs 7.8%). Mechanical ventilation had greater short term effectiveness in patients with COPD, based on survival to hospital discharge (76% vs 38%). Patients with COPD maintained higher median 2-month and 6-month survival prognoses, even days before death.
CONCLUSIONS - Hospitalized patients with lung cancer or COPD preferred comfort-focused care, yet dyspnea and pain were problematic in both groups. Patients with COPD were more often treated with life-sustaining interventions, and short-term effectiveness was comparatively better than in patients with lung cancer. In caring for patients with severe COPD, consideration should be given to implementing palliative treatments more aggressively, even while remaining open to provision of life-sustaining interventions.
STUDY OBJECTIVES - The purpose of this cross-sectional study was to confirm the observation that pulse oximetry tracing correlates with pulsus paradoxus, and is therefore a measure of the severity of air trapping in obstructive airway disease.
DESIGN - Cross-sectional survey.
SETTING - The ICU in a tertiary care academic hospital.
PATIENTS - Twenty-six patients consecutively admitted to the ICU with obstructive airway disease, either asthma or COPD.
MEASUREMENTS AND RESULTS - Forty-six percent of the study patients required mechanical ventilation, and 69% had an elevated pulsus paradoxus. We defined the altered pulse oximetry baseline tracing as the respiratory waveform variation (RWV). The RWV was measured in numerical form as the change in millimeters from the baseline. Pulsus paradoxus was significantly correlated with the RWV of the pulse oximetry tracing (p < 0.0001). An analysis of the respiratory variations in the pulse oximetry waveforms in obstructive lung disease patients reflects the presence and degree of auto-positive end-expiratory pressure (auto-PEEP; p < 0.0001).
CONCLUSIONS - We describe the characteristic alterations in the pulse oximetry tracings that occur in the presence of pulsus paradoxus and auto-PEEP. Since pulse oximetry is available universally in ICUs and emergency departments, it may be a useful noninvasive means of continually assessing pulsus paradoxus and air trapping severity in obstructive airway disease patients.
Factors associated with orthostatic blood pressure change in elderly outpatients were determined by surveying 398 medical clinical outpatients aged 65 years and older. Blood pressure was measured with random-zero sphygmomanometers after patients were 5 minutes in a supine and 5 minutes in a standing position. Orthostatic blood pressure changes were at normally distributed levels with systolic and diastolic pressures dropping an average of 4 mm Hg (standard deviation [SD]=15 mm Hg) and 2 mm Hg (SD=11 mm Hg), respectively. Orthostatic blood pressure changes were unassociated with age, race, sex, body mass, time since eating, symptoms, or other factors. According to multiple linear regression analysis, supine systolic pressure, chronic obstructive pulmonary disease (COPD), and diabetes mellitus were associated with a decrease in systolic pressure on standing. Hypertension, antiarthritic drugs, and abnormal heartbeat were associated with an increase in systolic pressure on standing. For orthostatic diastolic pressure changes, supine diastolic pressure and COPD were associated with a decrease in diastolic pressure on standing. Congestive heart failure was associated with an increase in standing diastolic pressure. Using logistic regression analysis, only supine systolic pressure was associated with a greater than 20-mm Hg drop in systolic pressure (n=53, prevalence=13%). Supine diastolic pressure and COPD were the only variables associated with a greater than 20-mm Hg drop in diastolic pressure (n=16, prevalence=4%). These factors may help physicians in identifying older persons at risk for having orthostatic hypotension.
In order to describe the outcomes of patients hospitalized with an acute exacerbation of severe chronic obstructive pulmonary disease (COPD) and determine the relationship between patient characteristics and length of survival, we studied a prospective cohort of 1,016 adult patients from five hospitals who were admitted with an exacerbation of COPD and a PaCO2 of 50 mm Hg or more. Patient characteristics and acute physiology were determined. Outcomes were evaluated over a 6 mo period. Although only 11% of the patients died during the index hospital stay, the 60-d, 180-d, 1-yr, and 2-yr mortality was high (20%, 33%, 43%, and 49%, respectively). The median cost of the index hospital stay was $7,100 ($4,100 to $16,000; interquartile range). The median length of the index hospital stay was 9 d (5 to 15 d). After discharge, 446 patients were readmitted 754 times in the next 6 mo. At 6 mo, only 26% of the cohort were both alive and able to report a good, very good, or excellent quality of life. Survival time was independently related to severity of illness, body mass index (BMI), age, prior functional status, PaO2/FI(O2), congestive heart failure, serum albumin, and the presence of cor pulmonale. Patients and caregivers should be aware of the likelihood of poor outcomes following hospitalization for exacerbation of COPD associated with hypercarbia.
Chronic airflow limitation (CAL) is a problem which causes much disability and the necessity for long-term care. This article discusses the clinical and psychosocial assessment of the patient with CAL as it relates to the goals of management: to optimize airflow; to minimize respiratory failure; to facilitate adaptation to chronic illness; and to develop appropriate coping skills.
We have presented a case of invasive cutaneous alternariosis in a patient receiving chronic oral steroid therapy. Alternaria must be considered in the differential diagnosis of any progressive cutaneous infection in an immunocompromised patient. Invasive maneuvers are often needed to confirm the diagnosis. Given the rarity of cases and lack of controlled clinical trials, firm therapeutic guidelines are not available. Clinicians are likely to encounter more such cases as the population of immunocompromised hosts grows.
BACKGROUND - Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium.
METHODS - We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls.
RESULTS - The 24-hour excretion of 11-dehydro-thromboxane B2 (a stable metabolite of thromboxane A2) was increased in patients with primary pulmonary hypertension and patients with secondary pulmonary hypertension, as compared with normal controls (3224 +/- 482, 5392 +/- 1640, and 1145 +/- 221 pg per milligram of creatinine, respectively; P less than 0.05), whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (a stable metabolite of prostacyclin) was decreased (369 +/- 106, 304 +/- 76, and 644 +/- 124 pg per milligram of creatinine, respectively; P less than 0.05). The rate of excretion of all metabolites in the patients with COPD but no clinical evidence of pulmonary hypertension was similar to that in the normal controls.
CONCLUSIONS - An increase in the release of the vasoconstrictor thromboxane A2, suggesting the activation of platelets, occurs in both the primary and secondary forms of pulmonary hypertension. By contrast, the release of prostacyclin is depressed in these patients. Whether the imbalance in the release of these mediators is a cause or a result of pulmonary hypertension is unknown, but it may play a part in the development and maintenance of both forms of the disorder.
Proteolysis of elastic fibers is central to the development of emphysema, and a simple, noninvasive assay of elastin degradation would be useful in diagnosis and in therapeutic monitoring. We have adapted an indirect enzyme-linked immunosorbent assay (ELISA) to determine plasma, urine, and bronchoalveolar lavage fluid (BALF) elastin peptide concentrations in nonsmokers, healthy smokers, and patients with chronic obstructive pulmonary disease (COPD). Plasma elastin peptide concentrations were significantly higher in subjects with COPD (66.8 +/- 5.8 ng/ml, n = 10) compared with nonsmokers (23.4 +/- 4.6 ng/ml, n = 12), and healthy smokers had intermediate values (36.0 +/- 6.8, n = 6), p less than 0.05. Urine values (both unadjusted and normalized to urine creatinine concentration) were approximately 10-fold higher than plasma in all subject groups, and the relative differences among groups were the same as for plasma with values of 910.8 +/- 105.6, 358.1 +/- 101.2, and 281.0 +/- 67.8 ng/ml for subjects with COPD (n = 10), healthy smokers (n = 6), and healthy nonsmokers (n = 12), respectively. Poor recovery of BALF in COPD subjects reduced differences in the BALF elastin peptide concentrations among subjects groups, although the healthy smokers and COPD subjects tended to have higher amounts. Assuming some dilution due to lavage technique, elastin peptide concentrations were estimated to be substantially higher in epithelial lining fluid than in plasma, suggesting lung as a significant source of elastin peptides in COPD. This is the first application of elastin peptide measurement to human urine or BALF, and we conclude that this assay in urine is useful in characterizing elastin turnover in patients with or at risk for emphysema.