Epidemiologic evidence linking antioxidant vitamins to pulmonary function and airway obstruction.
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Airway Obstruction↗
Biomedical subjects
B J Grant
Publications and source records attributed to B J Grant.
The relation of serum levels of antioxidant vitamins C and E, retinol and carotenoids with pulmonary function in the general population.
Reduced pulmonary function is an important predictor of mortality in the general population, and antioxidant vitamins are thought to positively influence pulmonary function. Vitamin C, vitamin E, retinol, and carotenoids are powerful antioxidants but information about the joint relation of serum levels of these antioxidants to pulmonary function is limited. We analyzed the association of FEV(1) and FVC with serum vitamins C and E, retinol, and carotenoids (beta-cryptoxanthin, lutein/zeaxanthin, beta-carotene, and lycopene) in a cross-sectional study. The analysis was carried out in a sample of 1,616 randomly selected residents of Western New York, USA, age 35 to 79 yr and free of respiratory disease. Lung function was adjusted for height, age, sex, and race and expressed as percentage of predicted normal FEV(1) (FEV(1)%) and FVC (FVC%). Participants in the lowest quartile of each of the serum antioxidants had consistently lower FEV(1)% and FVC% than those in higher quartiles. Multiple linear regression analysis revealed significant associations of vitamin C, vitamin E, beta-cryptoxanthin, lutein/zeaxanthin, beta-carotene, and retinol with FEV(1)% when these variables were investigated individually after adjustment for other covariates (smoking status, pack-years of smoking, weight, eosinophil count, and education). When all of these antioxidant vitamins were analyzed simultaneously in a multivariate regression model, the strongest association was seen with vitamin E and beta-cryptoxanthin. Only retinol showed an independent effect on FEV(1)% after controlling for vitamin E and beta-cryptoxanthin. As for FEV(1)%, vitamin E and beta-cryptoxanthin were most strongly related to FVC% when all variables were considered in the multivariate regression model. The differences in FEV(1) associated with a reduction of one standard deviation of serum vitamin E or beta-cryptoxanthin were equivalent to the negative influence of approximately 1 to 2 yr of aging. Our findings support the hypothesis that antioxidant vitamins may play a role in respiratory health and that vitamin E and beta-cryptoxanthin appear to be stronger correlates of lung function than other antioxidant vitamins.
Adult↗
Clinical suspicion of fatal pulmonary embolism.
BACKGROUND: Less than one third of patients with fatal pulmonary embolism (PE) are identified prior to autopsy. OBJECTIVE: To determine whether the clinical syndromes of acute PE are effective at identifying patients who die of this condition. METHOD: Seven hundred seventy-eight autopsy reports at the Buffalo General Hospital from 1991 to 1996 inclusive were reviewed. Inpatient medical records of 67 patients who were identified as having PE as the primary or major cause of death then were analyzed. RESULTS: Thirty patients (45% [95% confidence interval, 33 to 57%]) had received a diagnosis of PE prior to death, which was marginally higher than the number previously reported (p < 0.05). The diagnosis of PE was significantly lower (13%; p < 0.01) in patients with COPD or coronary artery disease (33%; p < 0.01). In contrast to the prospective investigation of PE diagnosis data, only a minority of patients (6%) presented with pleuritic pain or hemoptysis, while a significantly larger proportion (24%; p < 0.01) of our patients experienced circulatory collapse. Only 55% were identified as having PE from the following clinical syndromes of PE: isolated dyspnea; pleuritic pain and/or hemoptysis; and circulatory collapse. Among the 30 patients suspected of having PE, only 14 (47%) received IV heparin in therapeutic doses, despite clinical suspicion. CONCLUSION: Our results show a modest increase in the correct antemortem diagnosis of fatal PE. The current clinical syndromes used as markers for suspecting PE are not sufficient to detect patients who ultimately die of PE. Physicians should maintain a higher index of suspicion since fatal PE does not always present as one of the three clinical syndromes of PE. Once PE is suspected, heparin therapy should be started early.
Aged↗
Pulmonary function is a long-term predictor of mortality in the general population: 29-year follow-up of the Buffalo Health Study.
STUDY OBJECTIVES: Results from several studies have described a relationship between pulmonary function and both all-cause and cause-specific mortality. The purpose of this study was to investigate the predictive value of pulmonary function by gender after 29 years of follow-up. DESIGN: Prospective study with 29-year follow-up of the Buffalo Health Study cohort. PARTICIPANTS: Randomly selected sample of 554 men and 641 women, aged 20 to 89 years, from all listed households of the city of Buffalo, NY. MEASUREMENTS AND RESULTS: Baseline measurements were performed in 1960 to 1961. Pulmonary function was assessed based on FEV(1) expressed as the normal percent predicted (FEV(1)%pred). FEV(1)%pred adjusted by age, body mass index, systolic BP, education, and smoking status was inversely related to all-cause mortality in both men and women (p<0.01). A sequential survival analysis in participants who had a survival time of at least 5, 10, 15, 20, and 25 years after enrollment in the study was also performed. Except for men who survived for > 25 years, we observed a statistically significant negative association between FEV(1)%pred and all-cause mortality. FEV(1)%pred was also inversely related to ischemic heart disease (IHD) mortality. When participants were divided into quintiles of FEV(1)%pred, participants in the lowest quintile of FEV(1)%pred experienced significantly higher all-cause mortality compared with participants in the highest quintile of FEV(1)%pred. For the entire follow-up period, the adjusted hazard ratios for all-cause mortality were 2.24 (95% confidence interval [CI], 1.60 to 3.13) for men and 1. 81 (95% CI, 1.24 to 2.63) for women, respectively. Hazard ratios for death from IHD in the lowest quintile of FEV(1)%pred were 2.11 (95% CI, 1.20 to 3.71) and 1.96 (95% CI, 0.99 to 3.88) for men and women, respectively. CONCLUSIONS: These results suggest that pulmonary function is a long-term predictor for overall survival rates in both genders and could be used as a tool in general health assessment.
Adolescent↗
Airway inflammation and etiology of acute exacerbations of chronic bronchitis.
STUDY OBJECTIVES: The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations. DESIGN: This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n = 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared. SETTING: An outpatient research clinic at a Veterans Affairs Medical Center. PATIENTS: These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations. H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB. CONCLUSIONS: Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB.
Acute Disease↗
Validity of neural network in sleep apnea.
Clinical assessment of obstructive sleep apnea (OSA) is poor. Overnight polysomnography (OPG) is the standard reference test, but it is expensive and time-consuming. We developed an artificial neural network (ANN) using anthropomorphic measurements and clinical information to predict the apnea-hypopnea index (AHI). All patients completed a questionnaire about sleep symptoms, sleep behavior, and demographic information prior to undergoing OPG. Neck circumference, height, and weight were obtained on presentation to the sleep center. Twelve variables were used as inputs. The output was an estimate of the AHI. The network was trained with a back-propagation algorithm on 189 patients and validated prospectively on 80 additional patients. Data from the derivation group was used to calculate the 95% confidence interval of the estimated AHI. Predictive accuracy at different AHI thresholds was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic curve. The c-index for predicting OSA in the validation set was 0.96 +/- 0.0191 SE, 0.951 +/- 0.0203 SE, and 0.935 +/- 0.0274 SE, using thresholds of > 10, > 15, and > 20/hour respectively. The actual AHI of the 80 patients in the validation data set fell within the 95% confidence limits of the values predicted by the ANN. This study suggests that ANN may be useful as a predictive tool for OSA.
Adolescent↗
Application of mortality prediction systems to individual intensive care units.
OBJECTIVE: To evaluate the predictive accuracy of the severity of illness scoring systems in a single institution. DESIGN: A prospective study conducted by collecting data on consecutive patients admitted to the medical intensive care unit over 20 months. Surgical and coronary care admissions were excluded. SETTING: Veterans Affairs Medical Center at Buffalo, New York. PATIENTS AND PARTICIPANTS: Data collected on 302 unique, consecutive patients admitted to the medical intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Data required to calculate the patients' predicted mortality by the Mortality Probability Model (MPM) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems were collected. The probability of mortality for the cohort of patients was analyzed using confidence interval analyses, receiver operator characteristic (ROC) curves, two by two contingency tables and the Lemeshow-Hosmer chi-square statistic. Predicted mortality for all three scoring systems lay within the 95 % confidence interval for actual mortality. For the MPM II, SAPS II and APACHE II, the c-index (equivalent to the area under the ROC curve) was 0.695 +/- 0.0307 SE, 0.702 +/- 0.063 SE and 0.672 +/- 0.0306 SE, respectively, which were not statistically different from each other but were lower than values obtained in previous studies. CONCLUSION: Although the overall mortality was consistent with the predicted mortality, the poor fit of the data to the model impairs the validity of the result. The observed outcome could be due to erratic quality of care, or differences between the study population and the patient population in the original studies. The data cannot be used to distinguish between these possibilities. To increase predictive accuracy when studying individual intensive care units and enhance quality of care assessments it may be necessary to adapt the model to the patient population.
APACHE↗
Predicting active pulmonary tuberculosis using an artificial neural network.
BACKGROUND: Nosocomial outbreaks of tuberculosis (TB) have been attributed to unrecognized pulmonary TB. Accurate assessment in identifying index cases of active TB is essential in preventing transmission of the disease. OBJECTIVES: To develop an artificial neural network using clinical and radiographic information to predict active pulmonary TB at the time of presentation at a health-care facility that is superior to physicians' opinion. DESIGN: Nonconcurrent prospective study. SETTING: University-affiliated hospital. PARTICIPANTS: A derivation group of 563 isolation episodes and a validation group of 119 isolation episodes. INTERVENTIONS: A general regression neural network (GRNN) was used to develop the predictive model. MEASUREMENTS: Predictive accuracy of the neural network compared with clinicians' assessment. RESULTS: Predictive accuracy was assessed by the c-index, which is equivalent to the area under the receiver operating characteristic curve. The GRNN significantly outperformed the physicians' prediction, with calculated c-indices (+/- SEM) of 0.947 +/- 0.028 and 0.61 +/- 0.045, respectively (p < 0.001). When the GRNN was applied to the validation group, the corresponding c-indices were 0. 923 +/- 0.056 and 0.716 +/- 0.095, respectively. CONCLUSION: An artificial neural network can identify patients with active pulmonary TB more accurately than physicians' clinical assessment.
AIDS-Related Opportunistic Infections↗
Clinical and radiographic manifestations of uncommon pulmonary nontuberculous mycobacterial disease in AIDS patients.
STUDY OBJECTIVE: To determine the clinical and radiographic findings of nontuberculous mycobacteria (NTM) other than Mycobacterium avium complex (MAC) and Mycobacterium kansasii in AIDS compared with non-AIDS patients. DESIGN: A retrospective chart review of all patients in whom NTM other than MAC complex and M kansasii were isolated between April 1, 1989, and October 31, 1995. SETTING: University-affiliated hospital. PATIENTS: Fifty-four patients met the criteria for uncommon pulmonary NTM disease: (1) repeated isolation of atypical mycobacterium in colony counts of > or = 3 from two or more sputum specimens; or isolation of the organism from transbronchial or open lung biopsy specimen with histologic changes suggestive of mycobacterial disease in the absence of other pathogens; and (2) either an abnormal chest radiograph, the cause of which had not been attributed to an active infection other than atypical mycobacterial disease; or the presence of one or more symptoms indicative of pulmonary disease coupled with exclusion of other illnesses with similar symptoms and signs. RESULTS: Thirty-five patients were HIV positive. Fever was the only clinical symptom more commonly seen in HIV-infected patients with NTM than non-HIV-infected patients. Sixty-six percent of all patients with AIDS were infected by Mycobacterium xenopi. Chest radiographs of AIDS patients showed a tendency for predominance of interstitial infiltrate and rarity of fibronodular disease. No specific radiographic pattern was observed for any particular organism. Adenopathy was not a feature of uncommon pulmonary NTM in AIDS, and it should suggest an alternate diagnosis. In two patients, NTM isolation from respiratory specimens preceded dissemination. Six of 8 AIDS patients treated for pulmonary NTM remained alive at the end of the study compared with only 4 of 15 patients who were not treated for pulmonary NTM (p<0.05). CONCLUSIONS: Uncommon NTM isolated from respiratory specimens ought to be considered as serious pathogens in the presence of clinical and radiographic manifestations unexplained by other pathologic processes. Colonization with NTM could precede dissemination. Treatment of uncommon pulmonary NTM disease could possibly confer a survival benefit in AIDS patients.
AIDS-Related Opportunistic Infections↗
Validity of a decision tree for predicting active pulmonary tuberculosis.
The recent outbreaks of multidrug-resistant strains of M. tuberculosis in health care facilities has increased concern over its transmission in health care facilities. Isolation has been recommended for all patients suspected to have tuberculosis even though the feasibility and the cost of this recommendation can be substantial. We have developed a classification tree using clinical and radiographic data from 277 isolation episodes in patients admitted between August 1992 and March 1994 who required isolation for suspicion of tuberculosis. The classification tree was developed with a sensitivity and negative predictive value of 100% by binary recursive partitioning to predict those patients who are unlikely to require isolation. The predictor variables were upper zone disease on chest radiograph, a history of fever, weight loss, and CD4 count. The tree was validated in a separate cohort of 286 isolation episodes between April 1994 and December 1995. In this validation cohort, no erroneous prediction was made of not isolating a patient with active pulmonary tuberculosis. The classification tree had a sensitivity of 100% (95% confidence interval [CI]: 92.5 to 100%), a specificity of 48.1% (95% CI: 43.8 to 52.4%), and a negative predictive value of 100% (95% CI: 98.5 to 100%). We estimate that the use of the tree could have reduced the number of patients requiring isolation by more than 40% without increasing the risk of cross infection.
CD4 Lymphocyte Count↗
Effect of hyperoxic hypercapnia on variational activity of breathing.
Dysrhythmias of breathing occur in several clinical disorders, but their mechanistic basis is obscure. To understand their pathophysiology, factors responsible for the variability of breathing need to be defined. We studied the effect of hyperoxic hypercapnia (CO2) on the variational activity of breathing in 14 volunteers before and after delivering CO2 nonobstrusively via a plastic hood. Compared with air, CO2 increased the gross variability of minute ventilation (VI) and tidal volume (VT), and decreased that of inspiratory time (TI) and expiratory time (TE) (all p < 0.03). CO2 increased the autocorrelation coefficient at a lag of one breath for VI (p < 0.05), the number of consecutive breath lags having significant autocorrelation coefficients for VI and VT (both p < 0.01), and the cycle time of oscillations in VI (p = 0.03) and VT (p = 0.04). Uncorrelated random behavior constituted > or = 80% of the variance of each breath component, correlated behavior represented 9 to 20%, and oscillatory behavior represented < 1% during both air and CO2. CO2 increased the correlated behavior of volume components, which was accompanied by development of low-frequency oscillations with a cycle time consistent with central chemoreceptor activation.
Adult↗
Clinical significance of pulmonary arterial input impedance.
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Humans↗
A comparison of severity of illness scoring systems for critically ill obstetric patients.
STUDY OBJECTIVE: To evaluate the predictive ability of three scoring systems, acute physiology and chronic health evaluation (APACHE II), simplified acute physiology score (SAPS II), and mortality probability models (MPM II) in critically ill obstetric patients compared to a control group of non-obstetric female patients of similar age group (range, 17 to 41 years). DESIGN: A retrospective medical chart review of obstetric and nonobstetric female patients between 17 and 41 years of age. SETTING: Two university hospitals. PATIENTS: Ninety-three obstetric patients and 96 nonobstetric female patients were identified from 12,740 consecutive ICU admissions. RESULTS: The actual mortality of the obstetric and the nonobstetric group was 10.8% (95% confidence interval [CI], 5.3 to 19.0%) and 12.5% (95% CI, 6.6 to 21.0%), respectively. The observed mortality was not statistically different from the mortality predicted by APACHE II, SAPS II, and MPM II (14.7%, 7.8%, and 9.1% for the obstetric group and 10.9%, 9.0%, and 9.9% for the nonobstetric group). Predictive accuracy was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic (ROC) curve. There were no significant differences in the c-index for APACHE II, SAPS II, and MPM II within or between the obstetric group ([mean +/- SE], 0.93 +/- 0.02, 0.90 +/- 0.04, and 0.91 +/- 0.04, respectively) and the nonobstetric group (0.97 +/- 0.02, 0.95 +/- 0.03, and 0.96 +/- 0.02, respectively). CONCLUSIONS: We conclude that APACHE II, SAPS II, and MPM II assess the ICU outcome of critically ill obstetric patients as accurately as nonobstetric critically ill female patients of similar age group.
APACHE↗
Time-varying pulmonary arterial input impedance via wavelet decomposition.
Wavelet decomposition is proposed as a novel approach for determining pulmonary arterial input impedance throughout the breathing cycle. The canine pulmonary arterial input impedance was evaluated throughout the ventilatory cycle at 5, 10, and 15 cmH2O of positive end-expiratory pressure. The impedance spectrum was obtained by Fourier transformation of wavelets generated by decomposing the pulmonary arterial pressure and flow waveforms. With wavelet decomposition, each heart beat is viewed individually as a transient pulse rather than as an interval within a continuous function of pressure and flow. The advantage of using this approach is the ability to obtain stable estimates of input impedance spectra with high-frequency resolution over the entire frequency range with only a limited data set of pressure and flow decomposed to wavelets as short as singular extrapolated cardiac cycles. This method was used to define the changes of input impedance that occur during the ventilatory cycle. Results show that the impedance spectrum undergoes notable changes during the breathing cycle and demonstrate the utility of the proposed method.
Animals↗
Determination of gas exchange threshold by nonparametric regression.
The gas exchange threshold (GET) has been used an an index of anaerobic threshold because it can be measured noninvasively. GET is estimated from a breakpoint in breath by breath values of carbon dioxide uptake (Vco2) and oxygen uptake (Vo2) obtained during a progressive exercise test. Three methods of estimating GET were evaluated: (1) the original V slope method (OVS) using two adjoining standard linear regressions, (2) the modified V slope method (MVS) where the breakpoint is detected by visual inspection, and (3) a new method that we developed with nonparametric regression (NPM) using cubic splines. Simulated data were used because the existence of a breakpoint is known with certainty. Detection accuracy for OVS and MVS never exceeded 63% because of a low specificity. The detection accuracy of NPM ranged between 50 and 89% depending on the amount of noise and abruptness of the threshold, and exceeded that of OVS and MVS at low levels of noise. NPM was significantly more accurate (p < 0.05) than OVS and MVS for detecting GET except with high levels of noise. Both NPM and OVS have similar degrees of numerical accuracy and are superior to the currently used MVS method in this respect. All three methods gave similar results on 20 exercise tests. We conclude from the simulated data that NPM is more accurate than OVS and MVS at detecting GET. NPM can be applied to human data and it provides results that are consistent with OVS and MVS.
Adult↗
Distribution of pulmonary capillary transit times.
The length of time that blood remains in the pulmonary capillary is an important variable in gas exchange. We have investigated the distribution of capillary transit times in isolated rabbit lungs perfused with a bicarbonate-free buffer. The time course of gas exchange was monitored by enclosing the lungs in a plethysmograph. A bolus of buffer containing dissolved acetylene was injected into the perfusion system. Exchange of this inert gas occurred as soon as the bolus reached the capillary bed, thereby describing the input function into the bed. A separate bolus injection of bicarbonate solution resulted in production and excretion of CO2 as long as the bolus remained in the capillary bed. The rate of CO2 production was adjusted by partial inhibition of endothelial carbonic anhydrase. The distribution of capillary transit times was computed from a model of CO2 production in the capillary bed and the observed rates and volumes of acetylene and carbon dioxide excretion. The recovered distributions indicate that there is a fairly wide distribution of capillary transit times (relative dispersion, 0.45) around the mean value of 1.71 s (+/- 0.53 [SD]). Only 10% of capillary transit times are less than one half of mean transit time. It is likely that gas exchange reaches equilibrium in the capillary bed except possibly during strenuous exercise or exposure to high altitude or in disease.
Acetylene↗
Beat-by-beat changes of viscoelastic and inertial properties of the pulmonary arteries.
We tested the hypothesis that pulmonary arterial input impedance varies during the ventilatory cycle due to alterations not only of the viscoelastic components of the pulmonary vasculature but also due to changes of the inertial components. A four-element lumped-parameter model was used to fit the pulmonary arterial pressure-flow recordings in the time domain in 10 anesthetized dogs. The four elements consisted of a resistor (R) that represents input resistance, a second resistor (R1) and a capacitor (C1) that represent the viscoelastic properties of the pulmonary vasculature, and an inductor (L1) that represents inertial properties of blood within the pulmonary vasculature. The parameters were evaluated at each heartbeat throughout the ventilatory cycle at three levels of positive end-expiratory pressure. All four parameters varied significantly during the ventilatory cycle. R, C1, L1, and R1 varied by up to 97, 33, 13, and 17%, respectively. Changes in parameter values were most apparent at the start of expiration when the most rapid changes of lung volume occur. This pattern of the results is consistent with the hypothesis that the time variation of pulmonary arterial impedance is due to dynamic shifts of blood volume between the extra-alveolar and alveolar arteries.
Animals↗
Noninvasive tests for acute venous thromboembolism.
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Acute Disease↗