Showing papers in "American Journal of Respiratory and Critical Care Medicine in 1998"
TL;DR: This paper presents experimental evidence for Increased Vascular Transmural Pressure Evidence for Alterations in Alveolar–Capillary Permeability Contributions of the Static and Dynamic Lung Volume Components to Ventilator-induced Edema High-volume Lung Edema Low Lung Volume Injury.
Abstract: Introduction: Ventilator-induced Lung Injury: Not Only Air Leaks Ventilation-induced Pulmonary Edema and Related Findings: A Historical Perspective Ventilation-induced Pulmonary Edema: Hydrostatic or Permeability Edema? Experimental Evidence for Increased Vascular Transmural Pressure Evidence for Alterations in Alveolar–Capillary Permeability Contributions of the Static and Dynamic Lung Volume Components to Ventilator-induced Edema High-volume Lung Edema Low Lung Volume Injury Effects of High-volume Ventilation on Abnormal Lungs Effects of High-volume Ventilation on Injured Lungs Interaction between Severe Alveolar Flooding and Mechanical Ventilation Effects of Resting the Lung on Ventilator-induced Lung Injury Possible Mechanisms of Ventilation-induced Lung Injury Mechanisms of Increased Vascular Transmural Pressure Mechanisms of Altered Permeability Clinical Relevance
2,259 citations
TL;DR: It is suggested that patient quality of life is related to COPD exacerbation frequency and factors predictive of frequent exacerbations were daily cough, daily wheeze, and daily cough and sputum.
Abstract: Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/- 0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/- 9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.
2,174 citations
TL;DR: In this article, a 6-min walk test was administered to 117 healthy men and 173 healthy women, aged 40 to 80 yr, to establish reference equations for prediction of the total distance walked during six minutes (6MWD) for healthy adults.
Abstract: In order to establish reference equations for prediction of the total distance walked during six minutes (6MWD) for healthy adults, we administered the standardized 6-min walk test to 117 healthy men and 173 healthy women, aged 40 to 80 yr. Oxygen saturation (SaO2), pulse rate, and the degree of dyspnea (Borg scale) were determined before and at the end of the walk. The median distance walked was 576 m for men and 494 m for women. The 6MWD was significantly less for men and women who were older and heavier, and for shorter men. The resulting gender-specific regression equations explained about 40% of the variance in the distance walked for healthy adults: for men, 6MWD = (7.57 x heightcm) - (5.02 x age) - (1.76 x weightkg) - 309 m, and for women, 6MWD = (2.11 x heightcm) - (2.29 x weightkg) - (5.78 x age) + 667 m. These reference equations may be used to compute the percent predicted 6MWD for individual adult patients performing the test for the first time, when using the standardized protocol.
1,760 citations
TL;DR: This work states that Idiopathic Pulmonary Fibrosis is a Specific Disease or a Histologic Manifestation of Many Diseases and AIP and UIP are Significance of NSIP.
Abstract: Background Pathologic Classification of Idiopathic Pulmonary Fibrosis UIP DIP/Respiratory Bronchiolitis Interstitial Lung Disease (RBILD) AIP NSIP Clinical Features of the Idiopathic Interstitial Pneumonias UIP DIP/RBILD AIP N SIP Grading of “Cellularity” and Fibrosis Relationship of UIP and DIP Relationship of AIP and UIP Significance of NSIP—A Specific Disease or a Histologic Manifestation of Many Diseases? Summary and Conclusions
1,233 citations
TL;DR: The study shows that the prevalence of sleep apnea tends to increase with age but that the clinical significance (severity) of apnea decreases, and that the sleep laboratory criteria used for diagnosis ofSleep apnea should be adjusted for age.
Abstract: The effects of age on the prevalence of sleep apnea in the general population remain unclear, because previous studies have focused on specific populations. The effects of age on the severity of apnea are unknown. This study was based on a two-stage general random sample of men (aged 20 to 100 yr), consisting of a telephone survey (n = 4,364) and a sleep laboratory evaluation of a survey subsample (n = 741). Obstructive sleep apnea (OSA), based on both sleep laboratory and clinical criteria (apnea/hypopnea index [AHI] > or = 10 and the presence of daytime symptoms) was found in 3.3% of the sample, with its maximum prevalence in the middle age group (45 to 64 yr). Also, based solely on laboratory criteria, the prevalence of OSA (obstructive AHI > or = 20) showed an age distribution similar to that of OSA diagnosed by laboratory and clinical criteria. The prevalence of any type of sleep apnea (central and obstructive) increased monotonically with age. However, central apnea appeared to account for this monotonic relationship with age. Severity of sleep apnea, as indicated by both number of events and minimum oxygen saturation, decreased with age when any sleep apnea criteria were used and when controlling for body mass index (BMI). The study shows that the prevalence of sleep apnea tends to increase with age but that the clinical significance (severity) of apnea decreases. On the basis of these findings, the sleep laboratory criteria used for diagnosis of sleep apnea should be adjusted for age.
1,199 citations
TL;DR: The objective of the study was to further unravel the prognostic significance of body weight changes in patients with COPD and to quantify the relationship between the baseline ...
Abstract: The objective of the study was to further unravel the prognostic significance of body weight changes in patients with COPD. Two survival analyses were performed: (1) a retrospective study, including 400 patients with COPD none of whom had received nutritional therapy; (2) a post hoc analysis of a prospective study, including 203 patients with COPD who had participated in a randomized placebo-controlled trial. There was no overlap between the patient groups. Baseline characteristics of all patients were collected on admission to a pulmonary rehabilitation center in stable clinical condition. In the prospective randomized placebo-controlled trial, the physiologic effects of nutritional therapy alone (n = 71) or in combination with anabolic steroid treatment (n = 67) after 8 wk was studied in patients with COPD prestratified into a depleted group and a nondepleted group. Mortality was assessed as overall mortality. The Cox proportional hazards model was used to quantify the relationship between the baseline ...
1,016 citations
TL;DR: Retrospective analysis of 104 patients with IPF who had open lung biopsy at Mayo Medical Center from 1976 to 1985 was performed to establish the overall survival rate, the spectrum of histopathological subgroups and their associated prognostic significance.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a generally fatal disorder with a reported median survival of 3 to 6 yr. This has been based on relatively few studies with diagnoses inconsistently confirmed by adequate lung biopsy. Retrospective analysis of 104 patients with IPF who had open lung biopsy (OLB) at Mayo Medical Center from 1976 to 1985 was performed to establish the overall survival rate, the spectrum of histopathological subgroups and their associated prognostic significance. The study group consisted of 54 men and 50 women with a median age of 63 yr. Median survival was 3.8 yr after diagnosis by OLB with an estimated 10 yr survival of 27%. Current histopathologic review showed a heterogeneous group including usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia/fibrosis (NSIP), acute interstitial pneumonia (AIP), bronchiolitis, bronchiolitis obliterans organizing pneumonia (BOOP), and others. Median survival of the UIP group was 2.8 yr which is significantly worse (p < 0.001) than for other subgroups of chronic interstitial pneumonias. IPF includes several histopathologic subgroups with significantly different survival rates. Patients with UIP have worse survival than patients with other types of idiopathic chronic interstitial pneumonias including NSIP. Accurate histopathologic classification is essential for prognostication in patients with IPF.
997 citations
TL;DR: The clinical and pathologic features of asbestosis and silicosis, and mineralogic features of asbestos and silica that may be important in disease causation along with confounding factors such as coexposures to smoking and/or other mineral dusts are considered.
Abstract: Interstitial pulmonary fibrosis caused by the inhalation of asbestos fibers or silica particles continues to be an important cause of interstitial lung disease. Although more stringent control of asbestos in the workplace and decreasing industrial use has contributed to declines in the prevalence of asbestosis in the United States (1), new cases continue to be identified. Similarly, silicosis is seen among sandblasters, underground miners, foundry and quarry workers, and in other dust-exposed trades (2). Both diseases, which may have relatively long latency periods, are observed in the clinic today, usually as a result of high occupational exposures in the past, and they are problematic in that treatment with corticosteroids and immunosuppressants, the usual approaches to therapy for fibrotic lung disease, is ineffective (3). Asbestos and silica are complex, naturally occurring minerals that are chemically and physically distinct. Moreover, the pathology of asbestosis and silcosis is dissimilar. However, the pathogenesis of these lesions and the major changes in pulmonary architecture, namely, the laying down of collagen in an interstitial location, appear to be similar to many of the features seen in idiopathic pulmonary fibrosis (IPF). Like IPF and representative animal models of IPF such as bleomycin instillation (4), both asbestosis and silicosis are characterized by a persistent inflammatory response and generation of proinflammatory and profibrotic mediators. Although asbestosis and silicosis have been studied intensely by basic and clinical research scientists, little is known about the crucial cellular mechanisms that initiate and drive the processes of inflammation and fibrogenesis. Many laboratories have developed animal and in vitro models of asbestosis and silicosis to elucidate the cellular events and properties of minerals important in disease causation. Others have explored confounding factors contributing to particulate-induced cell injury as well as cellular and molecular defense mechanisms in response to these minerals. This information has been used to modulate inflammation and fibrosis in expermental animal models in attempts to develop more effective treatment regimens for pulmonary fibroses. This review will briefly address the clinical and pathologic features of asbestosis and silicosis, and consider the mineralogic features of asbestos and silica that may be important in disease causation along with confounding factors such as coexposures to smoking and/or other mineral dusts. The relationship of particle number, type, and size to disease patterns will be reviewed. We will then summarize data published within the past 5 yr on cellular and molecular mechanisms of asbestosis and silicosis and preventive approaches to these diseases in experimental animal models. Lastly, we emphasize in our SUMMARY AND CONCLUSIONS the common mediators and cell types affected in the pathogenesis of both mineral-related and other forms of pulmonary fibrosis and plausible interrelationships between the development of fibrosis and lung cancer, a disease linked to occupational exposures to asbestos and possibly to exposures to silica (1, 5).
885 citations
TL;DR: Differences in the potential efficacies against microorganisms of 15 antimicrobial regimens were studied to provide a more rational basis for selecting the initial therapy of patients suspected of having VAP.
Abstract: To determine risk factors for ventilator-associated pneumonia (VAP) caused by potentially drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and/or Stenotrophomonas maltophilia, 135 consecutive episodes of VAP observed in a single ICU over a 25-mo period were prospectively studied. For all patients, VAP was diagnosed based on results of bronchoscopic protected specimen brush (> or = 10(3) cfu/ml) and bronchoalveolar lavage (> or = 10(4) cfu/ml) specimens. Seventy-seven episodes were caused by "potentially resistant" bacteria and 58 episodes were caused by "other" organisms. According to logistic regression analysis, three variables among potential factors remained significant: duration of mechanical ventilation (MV) > or = 7 d (odds ratio [OR] = 6.0), prior antibiotic use (OR = 13.5), and prior use of broad-spectrum drugs (third-generation cephalosporin, fluoroquinolone, and/or imipenem) (OR = 4.1). Distribution of the 245 causative bacteria was analyzed according to four groups defined by prior duration of MV ( or = 7 d) and prior use or lack of use (within 15 d) of antibiotics. Although 22 episodes of early-onset VAP in patients receiving no prior antibiotics were caused by antibiotic-susceptible bacteria, 84 episodes of late-onset VAP in patients receiving prior antibiotics were mainly caused by potentially resistant bacteria. Differences in the potential efficacies (ranging from 100% to 11%) against microorganisms of 15 antimicrobial regimens were studied according to classification into these four groups. These findings may provide a more rational basis for selecting the initial therapy of patients suspected of having VAP.
857 citations
TL;DR: The hypothesis that mechanical ventilation may play a pivotal (and hereto unrecognized) role in the initiation and/or propagation of a systemic inflammatory response leading to MSOF in certain patients is explored.
Abstract: Few problems facing the intensivist are as frustrating or as difficult to manage as multiple system organ failure (MSOF). While the precise etiology remains unknown, an integral feature is the development of a rampant systemic inflammatory response that persists unabated by host control mechanisms. Either a single massive insult, or a series of less intense insults (i.e., “two-hits”) appear to be necessary to overwhelm the individuals innate regulatory mechanisms. Often the lung is the first organ to fail, leading to initiation (or continuation) of ventilatory support. Although in some patients a precipitating nidus of infection or inflammation is identifiable, and lung injury is simply the first clinically evident manifestation of a systemic process, there remain a large number of patients in whom the explanation for progression from respiratory failure to multiple system organ failure is unclear. In this Perspective, we explore the hypothesis that mechanical ventilation may play a pivotal (and hereto unrecognized) role in the initiation and/or propagation of a systemic inflammatory response leading to MSOF in certain patients. We address this issue by examining the following questions: Can mechanical ventilation initiate or exacerbate lung injury/inflammation? Can lung injury/inflammation lead to systemic inflammation? Is there evidence of MSOF secondary to mechanical ventilation?
837 citations
TL;DR: In COPD, the distribution of peripheral muscle weakness and the correlation between quadriceps strength and the degree of airflow obstruction suggests that chronic inactivity and muscle deconditioning are important factors in the loss in muscle mass and strength.
Abstract: Peripheral muscle weakness is commonly found in patients with chronic obstructive pulmonary disease (COPD) and may play a role in reducing exercise capacity. The purposes of this study were to evaluate, in patients with COPD: (1) the relationship between muscle strength and cross-sectional area (CSA), (2) the distribution of peripheral muscle weakness, and (3) the relationship between muscle strength and the severity of lung disease. Thirty-four patients with COPD and 16 normal subjects of similar age and body mass index were evaluated. Compared with normal subjects, the strength of three muscle groups (p < 0.05) and the right thigh muscle CSA, evaluated by computed tomography (83.4 +/- 16.4 versus 109.6 +/- 15.6 cm2, p < 0.0001), were reduced in COPD. The quadriceps strength/thigh muscle CSA ratio was similar for the two groups. The reduction in quadriceps strength was proportionally greater than that of the shoulder girdle muscles (p < 0.05). Similar observations were made whether or not patients had been exposed to systemic corticosteroids in the 6-mo period preceding the study, although there was a tendency for the quadriceps strength/thigh muscle CSA ratio to be lower in patients who had received corticosteroids. In COPD, quadriceps strength and muscle CSA correlated positively with the FEV1 expressed in percentage of predicted value (r = 0.55 and r = 0. 66, respectively, p < 0.0005). In summary, the strength/muscle cross-sectional area ratio was not different between the two groups, suggesting that weakness in COPD is due to muscle atrophy. In COPD, the distribution of peripheral muscle weakness and the correlation between quadriceps strength and the degree of airflow obstruction suggests that chronic inactivity and muscle deconditioning are important factors in the loss in muscle mass and strength.
TL;DR: It is concluded that smokers who develop symptoms of chronic bronchitis and chronic airflow limitation have an increased number of CD8+ T-lymphocytes and an increased smooth muscle area in the peripheral airways as compared with asymptomatic smokers with normal lung function, supporting the important role of CD4+ and CD8+, as well as airway remodeling in the pathogenesis of chronic obstructive pulmonary disease.
Abstract: To investigate whether the inflammatory process in peripheral airways is different in smokers who develop symptoms of chronic bronchitis and chronic airflow limitation and in asymptomatic smokers who do not develop chronic airflow limitation, we examined surgical specimens obtained from 16 smokers undergoing lung resection for localized pulmonary lesions. Nine had symptoms of chronic bronchitis and chronic airflow limitation and seven were asymptomatic with normal lung function. In peripheral airways, immunohistochemical methods were performed to identify neutrophils, macrophages, CD4+ and CD8+ T-lymphocytes infiltrating the airway wall, and morphometric methods were used to measure the internal perimeter, the airway wall area, and the smooth muscle area. The number of CD8+ T-lymphocytes and the smooth muscle area were increased in smokers with symptoms of chronic bronchitis and chronic airflow limitation as compared with asymptomatic smokers with normal lung function, while the number of neutrophils, mac...
TL;DR: The different respiratory mechanics and response to PEEP observed are consistent with a prevalence of consolidation in ARDSp as opposed to prevalent edema and alveolar collapse in ARDSexp.
Abstract: To assess the possible differences in respiratory mechanics between the acute respiratory distress syndrome (ARDS) originating from pulmonary disease (ARDSp) and that originating from extrapulmonary disease (ARDSexp) we measured the total respiratory system (Est,rs), chest wall (Est,w) and lung (Est,L) elastance, the intra-abdominal pressure (IAP), and the end-expiratory lung volume (EELV) at 0, 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) in 12 patients with ARDSp and nine with ARDSexp. At zero end-expiratory pressure (ZEEP), Est,rs and EELV were similar in both groups of patients. The Est,L, however, was markedly higher in the ARDSp group than in the ARDSexp group (20.2 +/- 5.4 versus 13.8 +/- 5.0 cm H2O/L, p < 0.05), whereas Est,w was abnormally increased in the ARDSexp group (12.1 +/- 3.8 versus 5.2 +/- 1.9 cm H2O/L, p < 0.05). The IAP was higher in ARDSexp than in ARDSp (22.2 +/- 6.0 versus 8.5 +/- 2.9 cm H2O, p < 0.01), and it significantly correlated with Est,w (p < 0. 01). Increasing PEEP to 15 cm H2O caused an increase of Est,rs in ARDSp (from 25.4 +/- 6.2 to 31.2 +/- 11.3 cm H2O/L, p < 0.01) and a decrease in ARDSexp (from 25.9 +/- 5.4 to 21.4 +/- 55.5 cm H2O/L, p < 0.01). The estimated recruitment at 15 cm H2O PEEP was -0.031 +/- 0.092 versus 0.293 +/- 0.241 L in ARDSp and ARDSexp, respectively (p < 0.01). The different respiratory mechanics and response to PEEP observed are consistent with a prevalence of consolidation in ARDSp as opposed to prevalent edema and alveolar collapse in ARDSexp.
TL;DR: It is concluded that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H 2O.
Abstract: Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H 2 O, using tidal volume (V T ) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using V T at 10 ml/kg or above and close to normal Pa CO 2 . Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different V T (7.1 6 1.3 versus 10.3 6 1.7 ml/kg at Day 1, p , 0.001) and plateau pressures (25.7 6 5.0 versus 31.7 6 6.6 cm H 2 O at Day 1, p , 0.001), resulting in different Pa CO 2 (59.5 6 15.0 versus 41.3 6 7.6 mm Hg, p , 0.001) and pH (7.28 6 0.09 versus 7.4 6 0.09, p , 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p 5 0.38), the duration of mechanical ventilation (23.1 6 20.2 versus 21.4 6 16.3 d, p 5 0.85), the incidence of pneumothorax (14% versus 12%, p 5 0.78), or the secondary occurrence of multiple organ failure (41% versus 41%, p 5 1). We conclude that no benefit could be observed with reduced V T titrated to reach plateau pressures around 25 cm H 2 O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H 2 O. Brochard L, Roudot-Thoraval F, Roupie E, Delclaux C, Chastre J, Fernandez-Mondejar E, Clementi E, Mancebo J, Factor P, Matamis D, Ranieri M, Blanch L, Rodi G, Mentec H, Dreyfuss D, Ferrer M, Brun-Buisson C, Tobin M, Lemaire F, the Multicenter Trial Group on Tidal Volume Reduction in ARDS. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome.
TL;DR: Limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs, and there is wide variation in end-of-life care.
Abstract: In some intensive care units (ICUs), fewer patients who die now undergo attempts at cardiopulmonary resuscitation (CPR), and many more have life support actively withdrawn prior to death than did a decade ago. To determine the frequency of withdrawal of life support, we contacted every American postgraduate training program with significant clinical exposure to critical care medicine, asking them prospectively to classify patients who died into one of five mutually exclusive categories. We received data from 131 ICUs at 110 institutions in 38 states. There were 6,303 deaths, of which 393 patients were brain dead. Of the remaining 5,910 patients who died, 1,544 (23%) received full ICU care including failed cardiopulmonary resuscitation (CPR); 1,430 (22%) received full ICU care without CPR; 797 (10%) had life support withheld; and 2,139 (38%) had life support withdrawn. There was wide variation in practice among ICUs, with ranges of 4 to 79%, 0 to 83%, 0 to 67%, and 0 to 79% in these four categories, respectively. Variation was not related to ICU type, hospital type, number of admissions, or ICU mortality. We conclude that limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs. There is wide variation in end-of-life care, and efforts are needed to understand practice patterns and to establish standards of care for patients dying in ICUs.
TL;DR: In this paper, the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV) was determined.
Abstract: Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy (paradoxical response) has previously been described as a rare occurrence. To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals (historical control; Group 3). In Group 1 patients, paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD: 15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative (PPD) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV. These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients. Furthermore, the skin test conversion after the initiation of ARV may have important public health implications.
TL;DR: In smokersThe severity of airflow limitation is correlated with the severity of airway inflammation and that severe airflow limitations is associated with an increased number of neutrophils, macrophages, NK lymphocytes, and MIP-1alpha+ cells in the bronchial mucosa.
Abstract: To investigate the relationship between airflow limitation and airway inflammation in smokers, we examined paraffin-embedded bronchial biopsies obtained from 30 smokers: 10 with severe airflow limitation, eight with mild/moderate airflow limitation, and 12 control smokers with normal lung function. Histochemical and immunohistochemical methods were performed to assess the number of inflammatory cells in the subepithelium and the expression of CC chemokines macrophage inflammatory protein (MIP)-1alpha and -1beta in the bronchial mucosa. Compared with control smokers, smokers with severe airflow limitation had an increased number of neutrophils (p < 0.02), macrophages (p < 0.03), and NK lymphocytes (p < 0.03) in the subepithelium, and an increased number of MIP-1alpha+ epithelial cells (p < 0.02). When all smokers were considered together, the value of FEV1 was inversely correlated with the number of neutrophils (r = -0.59, p < 0.002), macrophages (r = -047, p < 0. 012), NK-lymphocytes (r = -0.51, p < 0.006) in the subepithelium, and with the number of MIP-1alpha+ epithelial cells (r = -0.61, p < 0.003). We conclude that in smokers the severity of airflow limitation is correlated with the severity of airway inflammation and that severe airflow limitation is associated with an increased number of neutrophils, macrophages, NK lymphocytes, and MIP-1alpha+ cells in the bronchial mucosa.
TL;DR: It is concluded that Borg dyspnea ratings, and measurements of IC and endurance time during submaximal cycle exercise testing are highly reproducible and responsive to change in severe COPD.
Abstract: Changes in lung hyperinflation, dyspnea, and exercise endurance are important outcomes in assessing therapeutic responses in chronic obstructive pulmonary disease (COPD). Therefore, we studied the reproducibility of Borg dyspnea ratings, inspiratory capacity (IC; to monitor lung hyperinflation), and endurance time during constant-load symptom-limited cycle exercise in 29 patients with COPD (FEV1 = 40 ± 2% predicted; mean ± SEM). Responsiveness was also studied by determining the acute effects of nebulized 500 μ g ipratropium bromide (IB) or saline placebo (P) on these measurements. During each of four visits conducted over an 8-wk period, spirometry and exercise testing were performed before and 1 h after receiving IB or P (randomized, double-blinded). Highly reproducible measurements included: endurance time (intraclass correlation R = 0.77, p 0.6, p < 0.0001); and slopes of Borg ratings over time, ox...
TL;DR: It is suggested that other factors (e.g., airway wall remodeling or autonomic dysfunction) may be responsible for most of the interindividual variability of airway responsiveness in asthma.
Abstract: In asthma, the acute increment of airway responsiveness caused by exposure to allergen is associated with influx of eosinophils into the airways. The relationship between chronic airway hyperresponsiveness and airway inflammation is unclear, as they do not change consistently following long-term anti-inflammatory treatments. We studied 71 patients with chronic asthma and allergic sensitization to perennial allergens. Airway responsiveness was determined by inhalation of methacholine, and airway inflammation was quantified by induced sputum (n = 28) or bronchoalveolar lavage (n = 43) and bronchial biopsy (n = 20). The relationships between airway responsiveness and the numbers of different inflammatory cells were assessed by multiple regression analysis. No significant correlations were found between the degree of airway responsiveness and the numbers of inflammatory cells in sputum or bronchoalveolar lavage or bronchial biopsy. By contrast, baseline lung function was inversely related to the numbers of eosinophils and directly related to the numbers of macrophages. The eosinophil cationic protein contents of either sputum or bronchoalveolar lavage were significantly correlated with the percentages of eosinophils but not with airway responsiveness. We suggest that other factors (e.g., airway wall remodeling or autonomic dysfunction) may be responsible for most of the interindividual variability of airway responsiveness in asthma.
TL;DR: The efficacy of EM treatment increased the survival rate of patients with DPB, which was more significant in the older than in the younger patients, and a significant difference in the survival rates between the two subgroups in Group c (p < 0.001).
Abstract: Diffuse panbronchiolitis (DPB) is a chronic inflammatory disease of the airways with a high rate of mortality despite treatment with a combination of antibiotics and the use of supportive therapy such as oxygen administration. Low-dose erythromycin therapy (EM) (400 to 600 mg/d) has been found to improve the survival of patients with DPB, and most patients with DPB in Japan have been treated with this erythromycin regime since 1984. The purpose of this study was to evaluate the effects of treatment with erythromycin on the survival rate of patients with DPB in Japan. We compared the survival rates of 498 patients with DPB after dividing them into three groups according to the date of their first medical examination (Group a: 1970-1979, Group b: 1980-1984, Group c: 1985-1990). DPB had been diagnosed in these patients using the criteria of the Ministry of the Health and Welfare Diffuse Lung Disease Committee (MHW-DLDC), which includes chronic productive cough, shortness of breath, presence of roentgenologically smoldering symmetrical granular shadows in the middle and lower lung fields, limitation of airflow without decrease in DLCO, elevated serum cold hemagglutinin titers, and/or narrowing bronchiolus with infiltration of lymphocytes and foamy alveolar macrophages. These patients were registered in the DPB research group of the Ministry of Health and Welfare (MHW). Survival rates were statistically compared using the generalized-Wilcoxon test. The survival rate of Group c was significantly higher than that of Groups a (p < 0.0001) and b (p < 0. 0001). In Group c, eight of 87 patients died; five died in the EM nontreated subgroup (n = 24), and three died in the EM-treated subgroup (n = 63). There was a significant difference in the survival rates between the two subgroups in Group c (p < 0.001). Treatment with EM was associated with a significant improvement in the rate of survival of patients with DPB. The efficacy of EM treatment increased the survival rate of patients with DPB, which was more significant in the older than in the younger patients.
TL;DR: Patients with IPF have a high prevalence of increased esophageal acid exposure, usually without typical GER symptoms, and acid reflux may be a contributing factor in the pathogenesis of IPF.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease (ILD) of unknown etiology. Introduction of acid into the respiratory tree can produce pulmonary fibrosis. Gastroesophageal reflux (GER) has previously been associated with several other respiratory conditions, including pneumonia, bronchitis, and asthma. To investigate prospectively the possible association of GER and IPF, 17 consecutive patients with biopsy-proven IPF and eight control patients with ILD other than IPF underwent dual-channel, ambulatory esophageal pH monitoring. Sixteen of 17 patients with IPF had abnormal distal and/or proximal esophageal acid exposure compared with four of eight control patients (p = 0.02). In the patients with IPF, mean percent distal total (13.6 versus 3.34, p = 0.006), distal upright (12.4 versus 5.1, p = 0.04), distal supine (14.7 versus 0.88, p = 0.02), and proximal supine (7.48 versus 0.24, p = 0.04) esophageal acid exposure times were significantly greater than those in control patients. Only four patients with IPF (25%) with increased acid exposure had typical reflux symptoms such as heartburn or regurgitation. Patients with IPF have a high prevalence of increased esophageal acid exposure, usually without typical GER symptoms. GER in these patients tends to occur at night and extend into the proximal esophagus. Acid reflux may be a contributing factor in the pathogenesis of IPF.
TL;DR: The high mortality for those reintubated for nonairway problems indicate that efforts should be preferentially focused on identifying these patients, and the effect of time to reintubsation suggests that identification of patients early after extubation and timely reinstitution of ventilatory support has the potential to reduce the increased mortality associated withextubation failure.
Abstract: Patients requiring reintubation after failed extubation have a poor prognosis, with hospital mortality exceeding 30 to 40%, though the reason remains unclear. To examine the impact of etiology of extubation failure and time to reintubation on hospital outcome, we performed a post hoc analysis of prospectively gathered data on 74 MICU patients (47 men, 27 women), 64 +/- 2 yr of age who required reintubation within 72 h of extubation. Cause for reintubation was classified as airway (upper airway obstruction, 11; aspiration/excess pulmonary secretions, 12) or nonairway (respiratory failure, 21; congestive heart failure, 17; encephalopathy, 7; other, 6). The duration of mechanical ventilation prior to extubation was 139 +/- 19 h, and the median time to reintubation was 21 h. Thirty-one of 74 patients (42%) died, with mortality highest for patients failing from nonairway etiologies (27/51, 53% versus 4/23, 17%; p 12 h, 25/49; p < 0.05). With multiple logistic regression, both cause for extubation failure and time to reintubation were independently associated with hospital mortality. In conclusion, etiology of extubation failure and time to reintubation are independent predictors of outcome in reintubated MICU patients. The high mortality for those reintubated for nonairway problems indicate that efforts should be preferentially focused on identifying these patients. The effect of time to reintubation suggests that identification of patients early after extubation and timely reinstitution of ventilatory support has the potential to reduce the increased mortality associated with extubation failure.
TL;DR: This Conference Report was prepared by a multidisciplinary ad hoc committee of the Assembly on Environmental and Occupational Health.
Abstract: This Conference Report was prepared by a multidisciplinary ad hoc committee of the Assembly on Environmental and Occupational Health.
TL;DR: The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathologic features of ALI that require resolution.
Abstract: The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last 10 years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathologic features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.
TL;DR: It is concluded that pathogens were more frequently present than previously reported in patients with severe exacerbations of chronic obstructive pulmonary disease and it may be advisable to obtain respiratory samples and to treat according to diagnostic results.
Abstract: We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance Quantitative cultures of tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and after 72 h, as well as serology for bacteria and respiratory viruses were performed Fifty patients (mean age 68 ± 8, 46 males) were studied prospectively Potentially pathogenic microorganisms (PPMs) and/or a positive serology were present in 36 of 50 (72%) patients, including 12 (33%) polymicrobial cases Only six (12%) had no pathogen in any sample in the absence of antimicrobial pretreatment Microbial patterns corresponded to community-acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in 19 o
TL;DR: B baseline Cst,w and its changes may play a role in determining the oxygenation response in the prone position; (2) theprone position improves CSt,rs and CST,L when the supine position is resumed.
Abstract: We studied 16 patients with acute lung injury receiving volume-controlled ventilation to assess the relationships between gas exchange and respiratory mechanics before, during, and after 2 h in the prone position. We measured the end-expiratory lung volume (EELV, helium dilution), the total respiratory system (Cst,rs), the lung (Cst,L) and the thoracoabdominal cage (Cst,w) compliances (end-inspiratory occlusion technique and esophageal balloon), the hemodynamics, and gas exchange. In the prone position, PaO2 increased from 103.2 +/- 23.8 to 129.3 +/- 32.9 mm Hg (p < 0.05) without significant changes of Cst,rs and EELV. However, Cst,w decreased from 204.8 +/- 97.4 to 135.9 +/- 52.5 ml/cm H2O (p < 0.01) and the decrease was correlated with the oxygenation increase (r = 0.62, p < 0.05). Furthermore, the greater the baseline supine Cst,w, the greater its decrease in the prone position (r = 0.82, p < 0.01). Consequently, the oxygenation changes in the prone position were predictable from baseline supine Cst,w (r = 0.80, p < 0.01). Returning to the supine position, Cst,rs increased compared with baseline (42.3 +/- 14.4 versus 38.4 +/- 13.7 ml/cm H2O; p < 0.01), mainly because of the lung component (57.5 +/- 25.1 versus 52.4 +/- 23.3 ml/cm H2O; p < 0.01). Thus, (1) baseline Cst,w and its changes may play a role in determining the oxygenation response in the prone position; (2) the prone position improves Cst,rs and Cst,L when the supine position is resumed.