Showing papers in "American Journal of Respiratory and Critical Care Medicine in 1994"

The American-European Consensus Conference on ARDS: Definitions, mechanisms, relevant outcomes, and clinical trial coordination

Abstract: The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.

Tidal ventilation at low airway pressures can augment lung injury.

Abstract: Intermittent positive pressure ventilation with large tidal volumes and high peak airway pressures can result in pulmonary barotrauma. In the present study, we examined the hypothesis that ventilation at very low lung volumes can also worsen lung injury by repeated opening and closing of airway and alveolar duct units as ventilation occurs from below to above the infection point (Pinf) as determined from the inspiratory pressure-volume curve. We ventilated isolated, nonperfused, lavaged rat lungs with physiologic tidal volumes (5 to 6 ml/kg) at different end-expiratory pressures (above and below Pinf) and studied the effect on compliance and lung injury. In the groups ventilated with positive end-expiratory pressure (PEEP) below Pinf compliance fell dramatically after ventilation. It did not change in either the control group or the group ventilated with PEEP above Pinf. Lung injury assessed morphologically was significantly greater in the groups ventilated with a PEEP below Pinf, and in these groups the ...

Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention.

Abstract: Treatment of Tuberculosis. 1. A 6-mo regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 mo followed by isoniazid and rifampin for 4 mo is the preferred treatment for patients with fully susceptible organisms who adhere to treatment. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should be included in the initial regimen until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (i.e., there is less than 4% primary resistance to isoniazid in the community, and the patient has had no previous treatment with antituberculosis medications, is not from a country with a high prevalence of drug resistance, and has no known exposure to a drug-resistant case). This four-drug, 6-mo regimen is effective even when the infecting organism is resistant to INH. This recommendation applies to both HIV-infected and uninfected persons. However, in the presence of HIV infection it is critically important to assess the clinical and bacteriologic response. If there is evidence of a slow or suboptimal response, therapy should be prolonged as judged on a case by case basis. 2. Alternatively, a 9-mo regimen of isoniazid and rifampin is acceptable for persons who cannot or should not take pyrazinamide. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should also be included until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (see Section 1 above). If INH resistance is demonstrated, rifampin and ethambutol should be continued for a minimum of 12 mo. 3. Consideration should be given to treating all patients with directly observed therapy (DOT). 4. Multiple-drug-resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended. 5. Children should be managed in essentially the same ways as adults using appropriately adjusted doses of the drugs. This document addresses specific important differences between the management of adults and children. 6. Extrapulmonary tuberculosis should be managed according to the principles and with the drug regimens outlined for pulmonary tuberculosis, except for children who have miliary tuberculosis, bone/joint tuberculosis, or tuberculous meningitis who should receive a minimum of 12 mo of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation

Abstract: Several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation, but their respective effects on the outcome of weaning from mechanical ventilation are not known. We conducted a randomized trial in three intensive care units in mechanically ventilated patients who met standard weaning criteria. Those who could not sustain 2 h of spontaneous breathing were randomly assigned to be weaned with T-piece trials, with synchronized intermittent mandatory ventilation (SIMV), or with pressure support ventilation (PSV). Specific criteria for performing tracheal extubation were defined for each modality. The number of patients who could not be separated from the ventilator at 21 d (i.e., who failed to wean) was compared between the groups. Patients in whom tracheal intubation was required in a 48-h period following extubation were also classified as failures. Among 456 mechanically ventilated patients who met weaning criteria, 109 entered into the study (35 with T piece, 43 with SIMV, and 31 with PSV). The three groups were comparable in terms of etiology of disease or characteristics at entry in the study. When all causes for weaning failure were considered, a lower number of failures was found with PSV than with the other two modes, with the difference just reaching the level of significance (23% for PSV, 43% for T piece, 42% for SIMV; p = 0.05). After excluding patients whose weaning was terminated for complications unrelated to the weaning process, the difference became highly significant (8% for PSV versus 33% and 39%, p < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

The biology of nitrogen oxides in the airways.

Abstract: Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung. The relationship between the toxicities and the bioactivities of NOx must be understood in the context of their chemical interactions in the pulmonary microenvironment. Nitric oxide synthase (NOS) is a newly identified enzyme system active in airway epithelial cells, macrophages, neutrophils, mast cells, autonomic neurons, smooth muscle cells, fibroblasts, and endothelial cells. The chemical products of NOS in the lung vary with disease states, and are involved in pulmonary neurotransmission, host defense, and airway and vascular smooth muscle relaxation. Further, certain patients with pulmonary hypertension, adult respiratory distress syndrome and asthma may experience physiologic improvement with NOx therapy, including inhalation of nitric oxide (NO.) gas. Both endogenous and exogenous NOx react readily with oxygen, superoxide, water, nucl...

The epidemiology of interstitial lung diseases.

Abstract: Little epidemiologic data are available on the occurrence of interstitial lung diseases (ILDs) in the general population. To describe the prevalence and incidence of ILDs a population-based registry of patients with ILDs was established in Bernalillo County, New Mexico in October 1988. All patients 18 yr of age and older who had a clinical diagnosis of an ILD were identified during the period 10/1/88 through 9/30/90 from physician referrals, hospital discharge diagnoses, histopathology reports, and death certificates. In addition, the prevalence of preclinical or undiagnosed cases was identified by screening lung specimens from 510 autopsy cases. A total of 2,936 referrals were screened; 8.8% were prevalent cases and 6.9% were incident cases. Overall, the prevalence of ILDs was 20% higher in males (80.9 per 100,000) than in females (67.2 per 100,000). Similarly the overall incidence of ILDs was slightly more common in males (31.5 per 100,000/year) than females (26.1 per 100,000/year). The estimated prevalence of preclinical or undiagnosed ILDs among all deaths was 1.8%. The most common incident diagnosed among both sexes were pulmonary fibrosis and idiopathic pulmonary fibrosis, together accounting for 46.2% of all ILD diagnoses in males and 44.2% in females. We conclude that the occurrence of ILDs in the general population may be more common than previous estimates based on selected populations, and these disorders may frequently be unrecognized.

Prevalence of Asthma and Atopy in Two Areas of West and East Germany

Abstract: The German reunification offers a unique opportunity to study the impact of environmental factors on the development of childhood respiratory and allergic disorders in ethnically similar populations. We investigated the prevalence of asthma, hay fever, atopy, and bronchial hyperresponsiveness (BHR) in 9- to 11-year old children in West Germany (n = 5,030) and East Germany (n = 2,623). A self-administered questionnaire was distributed to the parents. Children underwent cold air challenge and allergy skin prick tests. Atopic sensitization was considerably more frequent in West German children than in their peers in East Germany (36.7% versus 18.2%; odds ratio [OR] = 2.6, p < 0.0001). The prevalence of current asthma and hay fever was significantly higher in West Germany when compared with that in East Germany (5.9% versus 3.9%; OR = 1.5, p < 0.0001 and 8.6% versus 2.7%; OR = 3.4, p < 0.0001, respectively). Bronchitis, however, was more prevalent in East Germany than in the western part of the country. The prevalence of BHR as assessed by cold air challenge was higher in West Germany compared with that in East Germany (8.3% versus 5.5%, OR = 1.6, p < 0.001). Logistic regression showed that the West German study area was no longer a significant independent determinant of asthma once sensitization to mites, cats, and pollen was taken into account. We conclude that sensitization to aeroallergens is strikingly more frequent in West Germany than in East Germany and this may explain the differences in the prevalence of asthma and hay fever between the two parts of the country.

Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.

Abstract: The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.

Airway eosinophilia in chronic bronchitis during exacerbations.

Abstract: To examine the nature and the degree of airway inflammation in chronic bronchitis during exacerbations, bronchial biopsies and sputum were obtained in 11 subjects with chronic bronchitis examined during an exacerbation, and in 12 subjects with chronic bronchitis examined under baseline conditions. All subjects were nonatopic. Lobar bronchial biopsies were assessed using histochemical and immunohistochemical techniques, and sputum was examined for differential cell counts of leukocytes. Subjects with bronchitis during exacerbations had, on average, 30-fold more eosinophils in their bronchial biopsies than did those examined under baseline conditions (p < 0.001). Although to a lesser extent, the numbers of neutrophils (p < 0.01), T-lymphocytes (CD3) (p < 0.05), VLA-1-positive cells (p < 0.01), and TNF-alpha positive cells (p < 0.05) were also increased during exacerbations. By contrast, the T-lymphocyte subpopulations (CD4 and CD8) and the numbers of macrophages, mast cells, IL-2R-positive cells, and IL-1 beta-positive cells were similar in the two groups of subjects, as well as the percentages of ICAM-1- and E-selectin-positive vessels. Eosinophils were also increased in sputum of subjects with exacerbations when compared with those examined under baseline conditions (p < 0.05). In conclusion, exacerbations of chronic bronchitis are associated with a marked airway eosinophilia and with a milder increase in the number of neutrophils, activated T-lymphocytes, and TNF-alpha-positive cells in the bronchial mucosa.

Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation.

Abstract: To determine the extent of airway infection and inflammation in adolescents and adults with cystic fibrosis (CF) who have mild lung disease and are without symptoms of active infection, we performed bronchoalveolar lavage (BAL) on 18 CF patients > or = 12 yr of age who were stable, appeared clinically well, and had mean (+/- SEM) FEV1 of 79 +/- 4% of predicted. We quantitated the bacteria, inflammatory cells, immunoglobulins, and mediators of inflammatory tissue damage in the epithelial lining fluid (ELF) of these patients and in 23 healthy control subjects. All CF patients were found to be infected with Pseudomonas aeruginosa, Staphylococcus aureus, and/or Haemophilus influenzae; no organisms were isolated from the control subjects. The mean number of cells in the ELF was 14 times greater in the CF patients than in the control subjects. Neutrophils constituted 57% of the recovered cells in the CF patients versus 3% in the control subjects, and their concentration was 380 times greater in the CF patients versus the control subjects. IgG, IgA, and IgM were 2.5 to 6 times greater in CF ELF versus that of control subjects. Abundant active elastase was present in the ELF of the CF patients (2.3 +/- 0.9 microM) despite threefold elevated levels of alpha 1-protease inhibitor (alpha 1-PI). No active elastase was detectable in the control subjects. alpha 1-PI was functional in CF as demonstrated by elevated elastase:alpha 1-PI complex (0.045 microM in CF versus 0.002 microM in control subjects). This active elastase caused proteolytic destruction of surface complement receptors on airway neutrophils in situ.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease.

Abstract: Unexplained weight loss is common in chronic obstructive pulmonary disease (COPD). Blood levels of tumor necrosis factor-alpha (TNF-alpha), a cytokine causing cachexia in laboratory animals, are elevated in various human diseases associated with weight loss. We therefore prospectively measured TNF-alpha serum levels (immunoradiometric assay) in patients with clinically stable COPD (n = 30; all male; mean age, 65 yr) whose weight was less (Group I; n = 16) or more (Group II; n = 14) than the lower limit of normal taken from Metropolitan Life Insurance Company tables. The patients had no cause known to elevate TNF-alpha serum levels; notably, they were not infected. Group I patients had unintentionally lost weight during the previous year, whereas the weight of Group II patients had not changed during the same period. The two groups had similar chronic airflow obstruction and arterial blood gas impairment; hyperinflation and reduction in diffusing capacity were more pronounced in Group I, but differences were not significant. TNF-alpha serum levels (pg/ml; mean [SD]) were significantly higher in Group I than in Group II (70.2 [100.0] versus 6.7 [6.4]; p < 0.001). Group II TNF-alpha serum levels did not differ significantly from those of healthy subjects (7.8 [3.9]), whereas those of Group I were significantly higher (p < 0.001). Because renal function was in the normal range, we conclude that increased TNF-alpha production--and not decreased TNF-alpha clearance--is a likely cause of weight loss in patients with COPD.

Gender differences in sleep disordered breathing in a community-based sample.

Abstract: Gender differences in the relative frequency of sleep-disordered breathing (SDB) have been observed in surveys of patient groups referred for clinical evaluation compared with population surveys. In this study, we assessed the associations of gender, SDB, and symptoms of SDB in 389 participants (16 to 84 yr of age) in an ongoing genetic-epidemiologic study of sleep apnea. Subjects included index probands with laboratory-confirmed obstructive sleep apnea syndrome (laboratory sample, n = 36) and their family members and neighbors (the community sample). SDB was assessed with overnight in-home monitoring of airflow, oximetry, heart rate, and chest wall impedance, and symptoms were assessed with standardized questionnaires. In the entire sample, SDB, defined as a respiratory disturbance index [RDI] > or = 15, was more prevalent among males (38%) than among females (15%) (p or = 15 was observed among 26% of males and 13% of females. In the laboratory sample, females tended to be younger and were significantly heavier than males. However, in the community sample, females with SDB were older than male apneic subjects (63.4 +/- 13.9 versus 47.2 +/- 15.6 years, mean +/- SD; p < 0.01), and included a majority of postmenopausal women (75%). No differences in body mass index were noted between males and females with SDB recruited from the community.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroids contribute to muscle weakness in chronic airflow obstruction.

Abstract: Twenty-one patients with chronic obstructive pulmonary disease (COPD) or asthma, admitted to our division because of exacerbation of their conditions and requiring intensified treatment with corticosteroids, underwent pulmonary function tests, tests of respiratory muscle function, measurement of quadricep strength, and a variety of anthropometric and biochemical measurements. All tests were performed the 10th day after admission. As expected, muscle strength and pulmonary function were interrelated. Surprisingly, the average daily dose of steroids taken in the previous 6 mo, which ranged from 1.4 to 21.3 mg (average 4.3 mg), was significantly related to inspiratory muscle strength (PImax) and a similar tendency was present for expiratory muscle strength (PEmax). Multiple regression analysis of the relationship between PImax and quadriceps force (QF) and steroid dose revealed that the average daily dose independently explained 32% of the variance in PImax and up to 51% of the variance in QF. These relationships were independent of the degree of bronchial obstruction estimated by percentage predicted FEV1. Other significant determinants were age, sex, and COPD for PImax and age, sex, and body weight for QF. The present study demonstrates that in patients with COPD or asthma, respiratory and peripheral muscle strength and steroid treatment are interrelated despite the relatively low doses administered. This observation imposes further limitations on the prolonged treatment of chronic airflow obstruction with systemic corticosteroids.

Likelihood ratios for a sleep apnea clinical prediction rule.

Abstract: Nocturnal polysomnography, the standard diagnostic test for sleep apnea, is an expensive and limited resource. In order to help identify the urgency of need for treatment, we determined which clinical features were most useful for establishing an accurate estimate of the probability that a patient had sleep apnea. Of 263 physician-referred patients, 200 were eligible for the study and 180 (90%) completed it. All patients had their histories recorded with a standard questionnaire, and underwent anthropomorphic measurements and nocturnal polysomnography. Sleep apnea was defined as more than 10 episodes of apnea or hypopnea per hour of sleep. Multiple linear and logistic regression models predictive of sleep apnea were compared with physicians' subjective impressions and previously reported models. Likelihood ratios were calculated for several levels of a sleep apnea clinical score produced by one of the linear models. Predictors of sleep apnea in the final model (R2 = 0.34) included neck circumference, hype...

Physiologic effects of positive end-expiratory pressure and mask pressure support during exacerbations of chronic obstructive pulmonary disease.

Abstract: To assess physiologic effects of continuous positive airway pressure (CPAP) and positive end-expiratory pressure (PEEP) during noninvasive pressure support ventilation (PSV) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), we measured in seven patients the breathing pattern, lung mechanics, diaphragmatic effort (PTPdi), and arterial blood gases under four conditions: (1) spontaneous breathing (SB); (2) CPAP; (3) PSV of 10 cm H2O; and (4) PSV plus PEEP (PEEP + PSV). CPAP and PEEP were set between 80 and 90% of dynamic intrinsic PEEP (PEEPidyn) measured during SB and PSV, respectively. PEEPidyn was obtained (1) from the decrease in pleural pressure (delta Ppl) preceding inspiration, and (2) subtracting the fall in gastric pressure (delta Pga) caused by relaxation of the abdominal muscles from the delta Ppl decrease. Abdominal muscle activity made PEEPidyn overestimated in almost all instances (p < 0.0001). PSV increased minute ventilation, improved gas exchange, and decreased PTPdi. PEEP added to PSV, likewise CPAP compared with SB, further significantly decreased the diaphragmatic effort (PTPdi went from 322 +/- 111 to 203 +/- 63 cm H2O.s) by counterbalancing PEEPidyn, which went from 5.4 +/- 4.0 to 3.1 +/- 2.3 cm H2O. These data support the use of low levels of PEEP (80 to 90% of PEEPidyn) to treat acute exacerbation of COPD by means of mask PSV.

Human airway ion transport. Part one.

Abstract: The proper homeostasis of the liquids that line the surfaces of the lung is vitally important for lung defense. During the past 20 years, data derived primarily from animal studies have indicated that ion transport by the pulmonary epithelium regulates the volume and the composition of these surface liquids. The role of pulmonary epithelial ion-transport systems in this activity can be viewed at two levels: (1) the requirement to regulate surface liquid volumes and composition relevant to the local environment, e.g., adjusting the height and composition of surface liquids to permit efficient function of the mucociliary clearance system in the airways; and (2) the requirement of the pulmonary epithelium to coordinate intrapulmonary surface liquid flow (i.e., so-called «axial» flow) between different pulmonary regions, e.g, alveolar and airway surfaces

Mechanism by which the prone position improves oxygenation in acute lung injury.

Abstract: The mechanism by which oxygenation improves when patients with ARDS are turned from supine to prone position is not known. From results of our previous studies we reasoned that (1) when supine, in the setting of lung injury, transpulmonary pressure will be less than airway opening pressure and (2) atelectasis will develop preferentially in dorsal lung areas, and (3) both ventilation and ventilation/perfusion ratios would improve in these regions on turning prone. To study this directly, we measured regional ventilation and perfusion using 81mKr and 99mTc-MAA, respectively, and single photon emission computed tomography, both prone and supine, in four control animals and four given oleic acid. After oleic acid, the prone position improved (1) oxygenation (mean +/- SD PaO2 = 140 +/- 112 versus 453 +/- 54 mm Hg), (2) median ventilation/perfusion ratios (0.77 versus 0.95), (3) ventilation/perfusion heterogeneity (coefficient of variation 86 +/- 15 versus 61 +/- 6), and (4) the gravitational ventilation/perfus...

Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes.

Abstract: All episodes of ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus were prospectively analyzed for a 30-mo period. Methicillin-sensitive S. aureus (MSSA) was isolated in 38 episodes and methicillin-resistant S. aureus (MRSA) in 11 others. The two groups were similar regarding sex, severity of underlying diseases, prior surgery, and presence of renal failure, diabetes, cardiopathy, and coma. MRSA-infected persons were more likely to have received steroids before developing infection (relative risk [RR] = 3.45, 95% confidence interval [CI] = 1.38-8.59), to have been ventilated > 6 d (RR = 2.03, 95% CI = 1.36-3.03), to have been older than 25 yr (RR = 1.50, 95% CI = 1.09-2.06), and to have had preceding chronic obstructive pulmonary disease (RR = 2.76, 95% CI = 0.89-8.56) than MSSA-infected patients. MSSA-infected persons were more likely than MRSA-infected patients to have cranioencephalic trauma (RR = 1.94, 95% CI = 1.22-3.09). All patients with MRSA VAP had previously received antibiotics, compared with only 21.1% of those with MSSA infection (p < 0.000001). The incidence of empyema was similar in both groups; nevertheless, the presence of bacteremia and septic shock was more frequent in the MRSA group. Finally, mortality directly related to pneumonia was significantly higher among patients with MRSA episodes (RR = 20.72, 95% CI = 2.78-154.35). This analysis was repeated for monomicrobial episodes, and the difference remained statistically significant. We conclude that MRSA and MSSA strains infect patients with different demographic profiles; previous antibiotic therapy is the most important risk factor for developing MRSA infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group.

Abstract: Maximal inspiratory pressure (MIP) was assessed in 4,443 ambulatory participants of the Cardiovascular Health Study, 65 yr of age and older, sampled from four communities. Maximal expiratory pressure (MEP) was also measured in 790 participants from a single clinic. Positive predictors of MIP included male sex, FVC, handgrip strength, and higher levels of lean body mass (or low bioelectric resistance). Negative predictors were age, current smoking, self-reported fair to poor general health, and waist size. Both participant and technician learning effects were noted, but there was no independent effect of race, hypertension, cardiovascular disease, or diabetes. A healthy subgroup was identified by excluding current smokers, those with fair to poor general health, or an FEV1 less than 65% of predicted. Mean values determined from the healthy group were 57/116 cm H2O (MIP/MEP) for women, and 83/174 for men. Lower limits of the normal range (fifth percentiles) were 45 to 60% of the mean predicted values. The r...

Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome.

Abstract: To characterize the evolution of inflammation in the adult respiratory distress syndrome (ARDS) and test the hypothesis that sustained alveolar inflammation is associated with a poor outcome in patients with ARDS, we performed fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) in 125 patients and compared BAL cells and protein concentrations in survivors and nonsurvivors. ARDS followed sepsis syndrome in 35 patients, major trauma in 41, and other causes in 49. When possible, BAL was performed on Days 3, 7, and 14 after the onset of ARDS. Sixty-five patients (52%) had more than one BAL. We first performed analyses on each BAL day using information from all 212 BAL in the 125 patients (cross-sectional analysis). All patients had increased leukocytes and total protein in the first BAL (Day 3 after onset of ARDS). In patients with ARDS following sepsis, the percentage of BAL polymorphonuclear leukocytes (PMN) was higher on Day 7 (p = 0.11) and particularly Day 14 (p = 0.02) in patients who died; there was a consistent trend of a higher PMN concentration on all days in patients who died then in those who lived. In patients with ARDS following trauma and other risks, however, BAL PMN measures did not distinguish survivors from patients who died. Analysis of serial data from the patients with more than one BAL showed that alveolar macrophages (AM) increased in survivors of ARDS, both in absolute numbers and as a percentage of total cells; this pattern was most pronounced in the sepsis patients. The cross-sectional data analysis suggests that sustained alveolar inflammation occurs frequently in patients with ARDS following sepsis and is associated with a high mortality.

Vertical gradient of regional lung inflation in adult respiratory distress syndrome.

Abstract: We obtained chest computed tomography (CT) sections in 12 normal subjects (controls) and 17 patients with the adult respiratory distress syndrome (ARDS) to investigate regional lung inflation. A basal CT section (just above the diaphragm) was obtained in the supine position at zero cm H2O end-expiratory pressure. In each CT section the distance from ventral to dorsal surface (hT) was divided into 10 equal intervals, and 10 lung levels from ventral (no. 1) to dorsal (no. 10) were defined. Knowing the average density and the volume of each level, we computed: (1) the tissue volume; (2) the gas/tissue (g/t) ratio (index of regional inflation); (3) the hydrostatic pressure superimposed on each level (SPL), estimated as density x height. The total volume of the basal CT section was 49 +/- 2.5 ml x m-2 (mean +/- SE) in control subjects and 43 +/- 2.3 ml x m-2 in patients with ARDS (p = not significant [NS]). The tissue volume, however, was 16.7 +/- 0.8 ml x m-2 in control subjects and 31.6 +/- 1.7 ml x m-2 in patients with ARDS (p < 0.01). The g/t ratio in level 1 averaged 4.7 +/- 0.5 in control subjects and 1.2 +/- 0.2 in patients with ARDS (p < 0.01), and this ratio decreased exponentially from level 1 to level 10, both in controls and patients with ARDS. The Kd constant of the exponential decrease was 13.9 +/- 1.3 cm in control subjects and 7.8 +/- 0.8 cm in patients with ARDS (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Protease-antiprotease imbalance in the lungs of children with cystic fibrosis.

Abstract: Cystic fibrosis (CF) is characterized in the lung by chronic purulent bronchitis culminating in pulmonary insufficiency. There is evidence to suggest that neutrophil elastase (NE) released by neutrophils on the respiratory epithelial surface plays a major role in the pathogenesis of this lung disease. This study sought to determine the age of onset of the chronic neutrophil-dominated inflammation in CF and the consequences to the NE-anti-NE screen on the respiratory epithelial surface of the CF lung. NE and anti-NE defensive molecules were evaluated in respiratory epithelial lining fluid (ELF) in 27 children with stable CF (1 to 18 yr of age). Despite normal antigenic concentrations of alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI), 25 of 27 children with CF had neutrophil-dominated inflammation (> 500 neutrophils/microliters ELF). Active NE was found in ELF in 20 of 27 children, including two of four aged 1 yr. Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded. These observations demonstrate that a chronic imbalance of the NE-anti-NE protective screen develops early on the respiratory epithelial surface in persons with CF and is likely well established by 1 yr of age, with resultant potential for lung damage.

A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists.

Abstract: The association between the use of inhaled beta-agonists and the risk of death and near-death from asthma has previously been reported. It was based on a nested case-control study of 129 cases and 655 control subjects selected from a cohort of 12,301 users of asthma drugs followed during the period 1980 through 1987. In this paper we examine the question of asthma and non-asthma mortality using data from the entire cohort of 12,301 asthmatics. There were 46 asthma and 134 non-asthma deaths in this cohort, for which there were 47,842 person-years of follow-up. The overall rate of asthma death was 9.6 per 10,000 asthmatics per year. This rate varied significantly according to the use of fenoterol, albuterol, or oral corticosteroids in the prior 12 months and the number of asthma hospitalizations in the prior 2 years. The rate decreased significantly, by 0.6 asthma deaths per 10,000 asthmatics per year over the study period, after controlling for the effect of the four other risk factors. It also increased significantly with the use of all beta-agonists, and more so for fenoterol than for albuterol, although this difference was partly explained by the dose inequivalence of the two drugs. Change-point dose-response curves showed that the risk of asthma death began to escalate drastically at about 1.4 canisters (of 20,000 micrograms each) per month of inhaled beta-agonist, the recommended limit. For non-asthma death, the overall rate of 28 deaths per 10,000 asthmatics per year was not related to the use of inhaled beta-agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of life in asthma. I. Internal consistency and validity of the SF-36 questionnaire.

Abstract: Asthma is a chronic disease in which social life is altered. The importance of restrictions on social life may be greater in severe asthma or when symptoms are not adequately controlled. General scales of quality-of-life (QOL) may be used to detect the importance of social life impairment, but it is not yet known whether the scores of such QOL measures are reliable and valid in asthmatic patients. A study was carried out in 252 patients with asthma of variable severity (FEV1 ranging from 25 to 131% of predicted) to assess the validity of a general QOL scale, the first French version of the SF-36 health status questionnaire (SF-36). This is based on 36 items selected to represent nine health concepts (physical, social, and role functioning; mental health; health perceptions; energy or fatigue; pain; and general health). All nine SF-36 category scores were highly significantly correlated with the severity of asthma assessed by the clinical score of Aas (p < 0.0007 to p < 0.0001). Eight SF-36 category scores were highly significantly correlated with FEV1 (p < 0.003 to p < 0.0001). A high internal reliability of SF-36 was found using the alpha coefficient of Cronbach (0.91 for the whole questionnaire). The SF-36 questionnaire is valid and reliable in asthma and can therefore be used to examine QOL in asthmatic and nonasthmatic patients and to determine to what extent asthma impairs social life.

Nasal CPAP: an objective evaluation of patient compliance.

Abstract: Nasal continuous positive airway pressure (NCPAP) improves sleepiness and prognosis in obstructive sleep apnea (OSA). Our objective was to document NCPAP compliance and the percentage of time that the effective pressure shown to eliminate 95% of the obstructive apneas and hypopneas was maintained. We built and covertly installed an elapsed timer and mask pressure transducer recorder in NCPAP units of 47 OSA patients. Subjects were seen at 2- to 8-wk intervals over 6 months. Group mean age was 51 yr; 38 males, with mean body mass index of 42; all complained of daytime sleepiness. Initial full night polysomnography demonstrated a mean apnea-hypopnea index (AHI) of 58 +/- 2.6 SEM (range, 10 to 115). Nine subjects discontinued therapy within 3 months for various reasons. In the remaining subjects (n = 38) the actual mean nightly hours of use was 4.7 which represents 68% of the stated total sleep time (compliance). However, effective mean hours of use was 4.3 which represents 91% of the time that prescribed effective pressure was maintained at the mask. The AHI did not correlate with compliance, but did correlate with effective use (R = 0.27048, p = 0.0006). Subjective initial complaints of daytime sleepiness correlated with compliance only during the first visit (R = 0.38590, p = 0.05). No predictors for compliance were found.

Measuring Adherence to Asthma Medication Regimens

Abstract: The failure of patients to adhere to physician-prescribed regimens, either pharmacologic or behavioral, has been well documented in medical literature. Poor adherence to asthma medication regimens has been repeatedly demonstrated in both children and adults, with rates of nonadherence commonly reported from 30 to 70%. Medication regimens for asthma care are particularly vulnerable to adherence problems because of their duration, the use of multiple medications, and the periods of symptom remission. The clinical effects of this nonadherence by asthmatic patients can include treatment failure, unnecessary and dangerous intensification of therapy, and costly diagnostic procedures, complications, and hospitalizations. Although the measurement of adherence is an important component of both medical and behavioral interventions to control asthma, relatively little research has directly addressed the reliability and validity of the measures most widely used to assess asthma medication compliance. This review will discuss methods and issues in the measurement of adherence in general, and where available, measures that have been specifically used in evaluating adherence to asthma medication. Common measures used to assess compliance with asthma medications include direct measures, which confirm the use of medication by assaying it in blood, urine, or saliva, or which confirm the to use a medication, such as observed skill in using a metered dose inhaler. Indirect measures infer use with varying degrees of reliability, by use of clinical judgment, self-report/asthma diaries, medication measurement, and electronic medication monitors. The uses and limitations of these measures will be discussed.

Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma

Abstract: The efficacy of 6 wk of therapy with oral ICI 204,219, a selective leukotriene D4 (LTD4) receptor antagonist, was evaluated in subjects with moderate asthma during a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. Subjects who entered the trial had been chronically treated for asthma with beta agonist alone or in combination with theophylline. Subjects were randomized to treatment with twice daily doses of ICI 204,219 (5, 10, or 20 mg) or placebo if they had an FEV1 between 40 and 75% of predicted values without bronchodilator therapy and a daytime asthma score > 10 (range 0 to 21 per wk) for 7 consecutive d. Efficacy was evaluated from the results of symptom assessments, pulmonary function tests, and rescue medication use. Of 276 subjects randomized to treatment, 266 (10 mg, n = 66; 20 mg, n = 67; 40 mg, n = 67; placebo, n = 66) were analyzed for efficacy. Diary card assessments showed that treatment with increasing doses of ICI 204,219 linearly improved five efficacy crite...