Showing papers in "The American review of respiratory disease in 1984"

Early lung cancer detection : results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study

Abstract: The Johns Hopkins Lung Project was designed to determine whether the addition of cytologic screening to the radiographic screening of high-risk volunteers could enhance the early detection of asymptomatic lung cancer and whether early therapeutic intervention in detected cases could significantly reduce the mortality from this disease. Male volunteers, 45 yr of age and older, who smoked at least 1 pack of cigarettes per day were recruited from the Baltimore metropolitan area. All of the 10,387 acceptable high-risk volunteers received annual chest radiographic screening. By random assignment, one half received cytologic examination of induced sputum in addition to the roentgenogram. This report describes the results of the initial screening. Compared with usual methods of clinical diagnosis, screening by both roentgenography and cytology identified a greater proportion of the lung cancer cases at an earlier stage. Screening by sputum cytology was found to improve the detection only of squamous cell carcinoma. In the dual-screen group, sputum cytology accounted for 28% of the detected cases, and resulted in 39% additional detection of lung cancer over that achieved by roentgenography. There was no corresponding decrease in prevalence. Lung cancers detected by cytology alone were found at very early stages. Although there has been an increase in average survival, much of this increase, if not all, may have resulted from lead-time and sampling bias.

Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study.

Abstract: The initial (prevalence) radiologic and cytologic screening for lung cancer in the Mayo Clinic study (Mayo Lung Project) involved 10,933 outpatients. All were men at high risk for lung cancer, but none were suspected of having it when they entered the Mayo Clinic. Screening identified 91 lung cancers (8.3 per 1,000 screened). Nearly two thirds of the prevalence lung cancers were detected by chest roentgenography alone. Half of these cancers were resected. Only a fifth of the cancers were detected by sputum cytologic examination alone; however, all but 1 of these were resected. Compared with a group of lung cancers encountered in contemporary clinical practice at the Mayo Clinic, the prevalence cancers were more than twice as likely to be (1) resectable, (2) postsurgical Stage I or II (AJCC), and (3) associated with survival 5 yr after treatment.

Prospective evaluation of the protected specimen brush for the diagnosis of pulmonary infections in ventilated patients.

Abstract: To determine the relative cultural accuracy of the bronchoscopic protected specimen brush (PSB) in ventilated patients, we compared this method in the same area of the lung with histologic and bacteriologic examinations of pulmonary specimens. The procedures were concluded just after death when the ventilator was still functioning. Samples via the PSB were taken from a branch of the anterior basal bronchus of the left lower lobe, and immediate left thoracotomy was performed to obtain peripheral specimens from the corresponding segment for quantitative cultures. Twenty-six patients were studied; 6 had histologically proved pneumonia. Using quantitative cultures, a correlation was evidenced between PSB and lung cultures, especially in the subgroup of patients who received no antibiotic during the week preceding their death. No pneumonia was observed when PSB cultures isolated no organisms in concentrations greater than 103 colony-forming units (cfu) per ml. The PSB cultures at a level of 103 cfu/ml identifi...

Human lung growth in late gestation and in the neonate.

Abstract: We studied the lungs of 42 infants dying of obstetrical accidents, acute infections, and trauma, who ranged in age from 19 wk gestation to 3 wk postpartum at 42 wk gestation. The earliest lungs (19 to 20 wk gestation) had smooth-walled respiratory channels lined by cuboidal epithelium. Between 22 and 24 wk gestation with further development of the acinus, these channels took on a wavy internal configuration. After 28 wk gestation the air spaces (saccules) of the developing acinus became subdivided by secondary crests. Alveolar development began in some infants as early as 32 wk and was uniformly present by 36 wk. Respiratory bronchioles were not present in any of our cases, including those in the immediate postnatal period. Quantitative studies showed a rapid increase in lung volume and alveolar surface area beginning at about 28 wk gestation (crown-rump length, 25 cm) coinciding with increasing complexity of the saccules. Surface area, lung volume, and total number of alveoli showed an exponential relationship to gestational age and crown-rump length. Air-space wall thickness showed a rapid decline starting at 28 wk gestation and is best related exponentially to age and crown-rump length. Volume proportions of air spaces increased steadily throughout gestation. The increase in bronchial and bronchiolar air and air-space dimensions correlated relatively poorly with age, and nonparenchyma remained a relatively constant volume proportion, regardless of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung volume dependence of pharyngeal cross-sectional area in patients with obstructive sleep apnea.

Abstract: We examined the relationship between lung volume and pharyngeal cross-sectional area in 9 obese patients with obstructive sleep apnea and 10 age-matched, obese subjects without sleep apnea. Pharyngeal area was measured in the upright, seated posture using an acoustic reflection technique. Measurements were made at a rate of 5 per second during a slow exhalation from total lung capacity (TLC) to residual volume (RV). In the control subjects, the mean +/- SE pharyngeal area was 5.6 +/- 0.2 cm2 at TLC, and decreased by 30 +/- 5% over the vital capacity range to 3.9 +/- 0.3 cm2 at RV. In contrast to the control subjects, in patients with obstructive sleep apnea, pharyngeal area was 5.0 +/- 0.2 cm2 at TLC, and decreased by 54 +/- 6% over the vital capacity range to 2.3 +/- 0.3 cm2 at RV. The difference in pharyngeal area between the patients and control subjects was significant at all lung volumes below TLC, as was the difference in the magnitude of change in pharyngeal area with change in lung volume. The results indicate that in obese patients with obstructive sleep apnea, pharyngeal cross-sectional area is abnormally small, and varies considerably with changes in lung volume. The beneficial effects of weight reduction in such patients may relate to the coincident increase in functional residual capacity, causing an increase in upper airway size.

A controlled trial of intermittent positive pressure breathing, incentive spirometry, and deep breathing exercises in preventing pulmonary complications after abdominal surgery.

Abstract: Controversy exists regarding the routine use of aids to lung expansion in the prevention of pulmonary complications after abdominal surgery. We prospectively randomized 172 patients into 1 of 4 groups: the control group (44 patients) received no respiratory treatment, the IPPB group (45 patients) received intermittent positive pressure breathing therapy for 15 min 4 times daily, the IS group (42 patients) was treated with incentive spirometry 4 times daily, and the DBE group (41 patients) carried out deep breathing exercises under supervision for 15 min 4 times daily. Roentgenographic changes, observed 24 h after surgery, were comparable in the 4 groups (20.5 to 36.6%). Pulmonary complications were defined as the development of 3 or more of 6 new findings: cough, phlegm, dyspnea, chest pain, temperature greater than 38 degrees C, pulse rate more than 100 beats/min. The frequency of development of pulmonary complications was 48% in the control group, 22% in the IPPB group (p less than 0.05), 21% in the IS group (p less than 0.05), and 22% in the DBE group (p less than 0.05). Side effects of respiratory treatment were observed only in the IPPB group (18%; p less than 0.05). Hospital stay in patients undergoing upper abdominal surgery was significantly shorter in the IS group (mean +/- SD, 8.6 +/- 3 days) than in the control group (13 +/- 5 days). This difference was not observed for the other 2 treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Sarcoidosis: epidemiology and prognosis. A 15-year European study.

Abstract: A 15-year study of patients with sarcoidosis is presented. In most patients, the disease was discovered at a general health screening examination. The mean total incidence among persons 15 yr of age or older was 19 per 100,000 per year (21.7 for women and 16.5 for men). There was a peak incidence in both sexes between the ages of 20 and 34, and in older women, there was a second but lower and broader peak. The frequency of symptoms was greater in older women than in other patients. The accumulated lifetime risk of sarcoidosis was 1.3% for women and almost 1% for men. Patients with Stage I sarcoidosis, i.e., with bilateral hilar adenopathy alone, had the best prognosis, with 50% of the patients showing a normal radiographic picture 15 months after the discovery of the disease. Among patients with Stage II sarcoidosis (both bilateral hilar adenopathy and pulmonary infiltration), it was 36 months before 50% returned to normal radiographically. Resolution of all radiographic evidence of the disease could still occur many years after the first pathologic findings were made on chest films.

Upper airway morphology in patients with idiopathic obstructive sleep apnea

Abstract: Fundamental to the pathogenesis of obstructive sleep apnea (OSA) is the interaction of physiologic and anatomic alterations of the upper airway. However, many patients with OSA have no identifiable abnormality of the upper airway, and they have been termed idiopathic. In an attempt to find a structural deviation in upper airway anatomy, we performed acoustic echography and cephalometric roentgenograms in 9 male patients with OSA and no clinical evidence of upper airway abnormality. Mean cross-sectional area of the pharynx by acoustic reflection was less in these patients (3.7 +/- 0.8 cm2) than in subjects in a control group (5.3 +/- 0.6 cm2) (p less than 0.001). Mean glottic cross-sectional area was less in the patient group (1.5 +/- 0.5 cm2) than in the control group (2.7 +/- 0.5) (p less than 0.001). There was a significant correlation between the number of apneas per sleep hour and pharyngeal cross-sectional area (r = 0.87, p less than 0.01). Cephalometric analysis indicated that the patients had smaller mandibles by a mean of 5.4 +/- 6.6 mm (p less than 0.05). The overall posterior displacement of the mandibular symphysis, which is representative of the skeletal support of the anterior pharyngeal wall and is dependent on both mandibular size and position, was highly significant (6.4 +/- 4.7 mm) (p less than 0.01). Furthermore, there was a significant correlation between the number of apnea episodes per sleep hour and the total posterior displacement (r = 0.67, p less than 0.05). This study indicates that patients with so-called idiopathic OSA may have an anatomic predisposition to the development of upper airway occlusion that may not be detectable on clinical examination.

Anticholinergic, antimuscarinic bronchodilators

Abstract: The anticholinergic, antimuscarinic compounds are potent and hitherto neglected bronchodilators. Although atropine itself has drawbacks, principally related to its rapid absorption and consequent systemic side effects, its quaternary ammonium congeners, atropine methonitrate and ipratropium bromide, are poorly absorbed. When given by inhalation, they are as effective bronchodilators as atropine is, but longer acting and much less prone to side effects. They act predominantly at a site that is different from adrenergic agents and thus afford an alternative, complementary approach to the treatment of airways obstruction. In stable asthmatic subjects, ipratropium is almost as potent a bronchodilator as beta 2-adrenergic agents are. In patients with chronic bronchitis and emphysema, it is more potent than beta 2-adrenergic agents are. In both conditions, its combination with other bronchodilators adds significantly to the level and duration of bronchodilatation. It may also be occasionally useful in counteracting bronchospasm caused by specific stimuli, such as cold air and exercise, and particularly that caused by inadvertent beta-adrenergic blockade. By inhalation, ipratropium is relatively free of side effects, even in doses as much as 20 times those that produce maximal bronchodilatation. It does not significantly affect mucus production, viscosity, or clearance, problems for which atropine is suspect. Nor does it produce tremor and tachycardia, as do adrenergic agents. It can also probably be safely used in patients with glaucoma and bladder neck obstruction, unlike atropine. Ipratropium will probably find its major application in the long-term management of chronic bronchitis and emphysema, and in asthmatic patients who are poorly controlled by, or who experience troublesome side effects from, adrenergic agents.

High Frequency Ventilation

Abstract: High-frequency ventilation (HFV) is a difficult subject to deal with because we still lack a definition of high frequency. Basically HFV comes in three flavors: high-frequency positive pressure ventilation (HFPPV) introduced by Jonzon et al. (1); high-frequency jet ventilation (HFJV) introduced by Klain et al. (2); and high-frequency oscillation (HFO) introduced by Lunkenheimer et al. (3). The definition of high frequency depends on the system: HFPPV generally operates at 60+/min, HFJV at 150+/min and HFO at 900+/min. They can all achieve effective gas exchange in the normal lung. There are, as yet, no good comparative studies between the systems, nor any convincing evidence that any of them are superior to conventional mechanical ventilation (CMV) in diffuse parenchymal lung disease with hypoxia in humans. Despite this there are compelling theoretical reasons to suspect that HFV may be superior to CMV in this group of diseases. CMV creates large phasic volume distensions in sick lungs which have a nonuniform distribution of compliance, inevitably creating local overdistension. This can, at the macroscopic level, lead to air leaks (pneumothorax, etc.) and at the microscopic level cause hyaline membrane formation. Therefore, a mode of ventilation which reduces the magnitude of the volume distension might reduce the degree of barotrauma.

Alteration in osmolarity of inhaled aerosols cause bronchoconstriction and cough, but absence of a permeant anion causes cough alone.

Abstract: To determine whether cough and bronchoconstriction result from alterations in the osmolarity or alterations in the ion concentration of inhaled aerosols and to determine if the specific ions in the aerosol are important, we had 9 subjects with mild asthma inhale various solutions while we recorded cough and measured specific airway resistance. To evaluate the effects of altering osmolarity and ion concentration separately, we administered aerosols of hypo-osmolar distilled water (0 mosm), iso-osmolar sodium chloride (308 mosm), iso-osmolar dextrose in water (308 mosm), hyperosmolar sodium chloride (1,232 mosm), and a hyperosmolar solution of dextrose and sodium chloride (1,232 mosm). To evaluate cough without bronchoconstriction, we had the subjects inhale metaproterenol before inhaling the same aerosols. To determine whether the absence of a specific ion was important in causing cough or bronchoconstriction, we had the subjects inhale iso-osmolar solutions of sodium bromide, sodium gluconate, and lysine monohydrochloride. We found that alteration in osmolarity away from iso-osmolarity of inhaled aerosols is a stimulus for bronchoconstriction in subjects with mild asthma. Absence of ions in the presence of iso-osmolarity is not a stimulus for bronchoconstriction, but the absence of a permeant anion is a stimulus for cough. Thus, we found that the responses of cough and bronchoconstriction to inhaled aerosols can be separated.

Contaminated condensate in mechanical ventilator circuits. A risk factor for nosocomial pneumonia

Abstract: We studied ventilator circuit colonization and condensate formation in 30 mechanical ventilators during the first 24 h after a circuit change. Parts of the circuit nearest the patient were more frequently contaminated and had the highest levels of colonization. There was rapid colonization of tubing after a circuit change; 33% of the ventilators were colonized at 2 h, 64% at 12 h, and 80% at 24 h. The median level of colonization at 24 h was 7 X 10(4) organisms/ml. Water condensate collected in the ventilator circuits at a mean rate of 30 ml/h (range, 10 to 60 ml/h). At 24 h, 80% of the condensate samples were contaminated at a median level of 2 X 10(5) organisms/ml. The bacteria isolated from the condensate usually correlated with organisms previously isolated from the patient's sputum, suggesting that the patient's oropharyngeal flora is the primary source of circuit colonization. Highly contaminated condensate in the ventilator circuit may be a significant risk factor for nosocomial pneumonia. We suggest that circuit condensate be emptied regularly, handled as infectious waste, and that special efforts be taken to prevent contaminated condensate from inadvertently washing into the patient's tracheobronchial tree.

Neutrophil depletion inhibits airway hyperresponsiveness induced by ozone exposure.

Abstract: We studied whether ozone-induced hyperresponsiveness could be inhibited by neutrophil depletion in dogs. Responsiveness was assessed with dose-response curves of acetylcholine aerosol versus pulmonary resistance; depletion was assessed by counting neutrophils in venous blood and in biopsies of the airway epithelium. Responsiveness and neutrophil numbers were determined 5 days and 1 day before ozone and 1 h after ozone (3.0 ppm, 2 h) in 6 untreated dogs and in 6 dogs treated with hydroxyurea (200 mg/kg daily for 5 days starting 5 days before ozone). In untreated dogs, responsiveness and neutrophil numbers 5 days and 1 day before ozone did not change, but responsiveness and epithelial neutrophils increased markedly after ozone. In treated dogs, circulating neutrophils decreased from 8.9 +/- 2.2 to 0.6 +/- 0.01 X 10(3) per mm3 (mean +/- SEM), and responsiveness before ozone did not change. Furthermore, increases in responsiveness and epithelial neutrophils did not occur after ozone. Six wk after stopping hydroxyurea, responsiveness and epithelial neutrophils increased markedly after ozone. The results suggest that ozone-induced hyperresponsiveness may depend on the mobilization of neutrophils into the airways.

Bacteremic nosocomial pneumonia. Analysis of 172 episodes from a single metropolitan area.

Abstract: We studied 172 episodes of bacteremia attributed to nosocomial pneumonia in 168 patients, observed in the 4 major hospitals of a single metropolitan area over a 5-yr period. Overall mortality for these patients was 58%. Deaths attributed directly to nosocomial pneumonia occurred almost exclusively in patients with serious and largely irreversible underlying diseases. These data confirm the high mortality associated with endemic hospital-acquired pneumonia. Although some deaths appear to be preventable, primarily by measures designed to reduce the risk of aspiration, analysis of the data herein raises doubts whether overall mortality can be significantly reduced by currently available measures.

Accurate quantification of cells recovered by bronchoalveolar lavage.

Abstract: Quantification of the differential cell count and total number of cells recovered from the lower respiratory tract by bronchoalveolar lavage is a valuable technique for evaluating the alveolitis of patients with inflammatory disorders of the lower respiratory tract. The most commonly used technique for the evaluation of cells recovered by lavage has been to concentrate cells by centrifugation and then to determine total cell number using a hemocytometer and differential cell count from a Wright-Glemsa-stained cytocentrifuge preparation. However, we have noted that the percentage of small cells present in the original cell suspension recovered by lavage is greater than the percentage of lymphocytes identified on cytocentrifuge preparations. Therefore, we developed procedures for determining differential cell counts on lavage cells collected on Millipore filters and stained with hematoxylin-eosin (filter preparations) and compared the results of differential cell counts performed on filter preparations with those obtained using cytocentrifuge preparations. When cells recovered by lavage were collected on filter preparations, accurate differential cell counts were obtained, as confirmed by performing differential cell counts on cell mixtures of known composition, and by comparing differential cell counts obtained using filter preparations stained with hematoxylin-eosin with those obtained using filter preparations stained with a peroxidase cytochemical stain. The morphology of cells displayed on filter preparations was excellent, and interobserver variability in quantitating cell types recovered by lavage was less than 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Chest wall mechanics during exercise in patients with severe chronic air-flow obstruction.

Abstract: We studied the dynamic mechanical properties of the chest wall in 7 patients with severe chronic air-flow obstruction (CAO) Measurements were made during quiet breathing at rest and during exercise on a bicycle ergometer at work rates equivalent to 50 and 100% of their maximal work rate (Ẇmax) The peak inspiratory pleural pressure relative to the chest wall relaxation curve (Pmus) increased from 135 ± 15 cm H2O at rest to 224 ± 17 cm H2O at Wmax, while the coincident transdiaphragmatic pressure increased from 97 ± 21 cm H2O at rest to 165 ± 23 cm H2O at Ẇmax Consequently, the coincident gastric pressure relative to its value during relaxation (Pab) was negative at rest (−45 ± 17 cm H2O) and became even more negative (−63 ± 23 cm H2O) at Ẇmax Yet the increase in ventilation with increasing exercise was associated with an increase in the passive outward displacement of the abdomen (ΔVab) relative to the total volume change (ΔVab + ΔVrc), such that the ratio ΔVab/(ΔVab + ΔVrc) increased from

Neonatal lung neutrophils and elastase/proteinase inhibitor imbalance

Abstract: Serial bronchoalveolar lavage (BAL) was performed prospectively on 10 normal control subjects, 20 Respiratory Distress Syndrome (RDS), and 11 Bronchopulmonary Dysplasia (BPD) newborn infants to evaluate the role of pulmonary inflammation in neonatal lung disease. Minimal inflammation was found in BAL at less than 24 h of life in all groups, but significant pulmonary polymorphonuclear leukocyte (PMN) influxes were noted at 96 h in RDS and BPD compared with control subjects. By 1 wk of life, BAL PMN counts returned to normal in RDS, but counts remained significantly elevated through 5 wk in BPD. Alveolar macrophage (AM) counts were significantly elevated at 96 h in RDS (p less than 0.05), but were significantly depressed in BPD at 4 and 5 wk (p less than 0.05). The BAL elastase/alpha 1-proteinase inhibitor (alpha 1Pi) ratios in RDS did not differ from those of normal control subjects; however, these ratios were significantly elevated from 1 through 4 wk of life in BPD, placing these infants at risk for proteolytic lung damage. Lavage elastase levels were elevated in both RDS and BPD, associated with a parallel increase in BAL alpha 1Pi in RDS and depressed BAL alpha 1Pi in BPD. These findings suggest that pulmonary inflammation, associated with a prolonged PMN influx and an imbalance between elastase and alpha 1Pi, may contribute to the development of the neonatal chronic lung disease, BPD.

Passive respiratory mechanics in newborns and children.

Abstract: When the Hering-Breuer reflex is used to relax the respiratory muscles, the passive compliance (Crs), resistance (Rrs), and time constant (Trs) of the respiratory system can be measured from the subsequent expiration. We used this method to assess 22 newborns with respiratory illness. Passive expirations were also recorded in 6 paralyzed, ventilated children. Using a simple slide valve, airway occlusion pressure was measured from a face mask or endotracheal tube, and expiratory flow was measured from a pneumotachygraph. In all subjects, there was a linear function of expiratory flow versus its integral, volume; by extrapolating the linear function to zero flow and zero volume (i.e., initial volume at time zero) Crs, Rrs, and Trs could be calculated; Crs was significantly reduced in mechanically ventilated versus spontaneously breathing infants, and Rrs was significantly higher in intubated versus extubated infants. During passive expiration in newborns, inspiration occurred at a volume above passive functional residual capacity. The passive expiratory flow-volume technique is simple, noninvasive, and appears to provide accurate measurements of respiratory mechanics in the newborn and in paralyzed children.

Mast cells in bronchoalveolar lumen of patients with bronchial asthma.

Abstract: Bronchoalveolar lavage was performed on patients with stable bronchial asthma to elucidate the existence and significance of mast cells in human bronchoalveolar lumen. The percentage of total mast cell population, in which 2 different types of mast cells could be identified morphologically in lavage fluids, was 0.25 +/- 0.19% (mean +/- SD) in asthmatic patients and 0.08 +/- 0.02% in control subjects. The number of mast cells in asthmatic patients was greater than in control subjects (p less than 0.05). The histamine content per mast cell in bronchoalveolar lumen was calculated to be 8.2 +/- 6.0 pg/cell in asthmatic patients and 15.3 +/- 10.8 pg/cell in control subjects, which suggests that the " releasability " of histamine is greater in asthmatic patients during asymptomatic periods than it is in control subjects, although the differences were not statistically significant. Our results suggest that an increase in the mast cell population of bronchoalveolar lumen is significant in the pathogenesis of bronchial asthma.

Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury.

Abstract: Neutrophil-mediated injury to lung parenchymal cells has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. As an in vitro model off neutrophil-mediate...

Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis.

Abstract: Activated T-lymphocytes play a central role in the alveolitis of pulmonary sarcoidosis by recruiting monocytes, the building blocks of granulomata, to the alveolar structures. The present study suggests that the lung mononuclear phagocyte population, which is derived from blood monocytes, may play a critical role in the pathogenesis of sarcoidosis by modulating local T-cell activation. In this regard, alveolar macrophages from sarcoid patients with high-intensity alveolitis released significantly greater amounts of lymphocyte-activating factor (interleukin-1), in vitro, than did macrophages from sarcoid patients with low-intensity alveolitis, patients with idiopathic pulmonary fibrosis, or normal control subjects (p less than 0.001, each comparison). Consistent with the concept that the lungs of sarcoid patients with low-intensity alveolitis may have a low level of inflammation present, alveolar macrophages from this group released more interleukin-1 than did macrophages from the normal group (p less than 0.05). These observations suggest that in pulmonary sarcoidosis: (1) mononuclear phagocytes are activated, and this state of activation correlates with the activity of the lung disease; (2) activated lung mononuclear phagocytes may modulate lung lymphocyte function, and thus play a critical role in the pathogenesis of this disease.

Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung.

Abstract: Leukotriene B4 (LTB4) is a lipoxygenase product of arachidonic acid that has potent chemotactic activity for blood leukocytes. To assess the potential role of LTB4 in lung inflammatory responses, we investigated the production of LTB4 by human alveolar macrophages and determined its chemotactic activity for lung and blood phagocytes in vitro and in vivo. Human alveolar macrophages were stimulated with the calcium ionophore A23187 (10 micrograms/ml), and lipoxygenase products in the supernatants were isolated by high-performance liquid chromatography. Leukotriene B4 was the predominant arachidonate lipoxygenase product from the alveolar macrophages of 2 nonsmokers (17.3 +/- 2.7 ng/10(6) cells) and 3 of 4 smokers (23.4 +/- 14.8 ng/10(6) cells). Alveolar macrophages produced more LTB4 than did similarly treated peripheral blood neutrophils. Stimulated alveolar macrophages also produced 5-hydroxyeicosatetraenoic acid (HETE) and 2 isomers of LTB4: 5-(S),12-(R)-6-trans-LTB4 and 5-(S),12-(S)-6-trans-LTB4. Leukotriene B4 showed little chemotactic activity for alveolar macrophages in vitro and was a more potent chemoattractant for peripheral blood neutrophils than for monocytes (p less than 0.05). When instilled into the airways of anesthetized rats, LTB4 was less potent as an attractant for neutrophils and mononuclear cells than either zymosan-activated serum or bacterial-derived chemotactic factors. Leukotriene B4 production by alveolar macrophages may provide a mechanism by which phagocytes are recruited to the human lung during inflammatory processes.

Streptococcus pneumoniae infections and bacteremia in patients with acquired immune deficiency syndrome, with report of a pneumococcal vaccine failure.

Abstract: Five patients had Streptococcus pneumoniae infections among the 35 hospitalized with acquired immune deficiency syndrome (AIDS) at the New York Veterans Administration Medical Center between January 1, 1982, and June 30, 1983. Three of these patients had pneumococcal bacteremia and 2 had pneumonia without bacteremia. Twenty-seven bacteremic S. pneumoniae infections occurred among 5,143 patients without AIDS admitted to the Medical Service of this hospital during the same period. Thus, pneumococcal bacteremia was more likely to occur in patients with AIDS than in the general hospitalized population (x2 = 26, p = < 0.001). Two of the bacteremic infections were caused by S. pneumoniae type 4. One of these occurred in a patient who had been inoculated with the 14 valent pneumococcal vaccine 5 months earlier. There were no significant differences in concentrations of radioimmunoassay antibody to type 4 pneumococcal polysaccharide in sequential serum samples collected from this patient, and opsonic titers to th...

Interaction between hyperosmolar and IgE-mediated histamine release from basophils and mast cells.

Abstract: Because both hyperosmolar and IgE-dependent stimuli may be encountered in the airway, and because hyperosmolarity causes histamine release in basophils, we examined the effects of the 2 stimuli on human lung mast cells. Mast cells prepared by enzymatic digestion of human lung were suspended in buffers made hyperosmolar with mannitol. Significant histamine release was seen above 360 mOsm/kg H2O, increasing to 11.9 +/- 1.0% at 770 mOsm/kg H2O, and release was synergistically enhanced by anti-IgE. Cells that had been rendered unresponsive to IgE-dependent stimuli by exposure to anti-IgE in the absence of Ca++ became markedly more responsive to hyperosmolar stimulation, and released as much as 32 +/- 2% histamine in hyperosmolar buffers alone. Antigen-induced histamine release from the basophils of allergic donors was also synergistically enhanced in buffers above 460 mOsm/kg H2O. These data show that immunologic and nonimmunologic stimuli may interact, and that human lung mast cells are capable of mediator release when exposed to osmolarities that may occur in the airway, especially during hyperventilation. Hyperosmolar mediator release is a plausible mechanism by which exercise-induced hyperventilation might induce asthma.

Biologically active products of complement and acute lung injury in patients with the sepsis syndrome.

Abstract: To determine if biologically active products of complement appear during sepsis and to establish the relationship of these components to the respiratory and hemodynamic complications of sepsis, we measured C5a des Arg and C3a des Arg (radioimmunoassay), neutrophil chemotaxis, and neutrophil-aggregating activity in plasma obtained from 40 patients at the time sepsis was suspected clinically. Levels of C3a des Arg and C5a des Arg were elevated in 35 and 38 patients, respectively, and in all 25 with positive blood cultures. Highest C5a des Arg levels occurred in patients with hypotension (less than 90 mmHg) and/or acidemia. The C5a des Arg concentrations were significantly higher in patients with than in those without neutrophil-chemotactic activity. Neutrophil-aggregating activity was less sensitive an index of complement activation, as it was positive in only 8 patients and correlated poorly with C5a des Arg and C3a des Arg values. Using a composite scoring system to quantify sepsis-related pulmonary abnormalities, we found that neither biologic nor immunologic assays of complement activation products correlated with the initial severity nor predicted the development or worsening of associated acute lung injury.

Long-term course of pulmonary arterial pressure in chronic obstructive pulmonary disease

Abstract: Ninety-three patients with severe chronic obstructive pulmonary disease (COPD) of the bronchitic (n = 74) or emphysematous type (n = 19), who all had arterial hypoxemia, underwent 2 right cardiac catheterizations in a clinical steady state, with a delay of 5 yr or more between the first and the last catheterization. No patients received long-term O2 therapy or pulmonary vasodilator drugs. Patients were divided into 2 groups according to the initial level of mean pulmonary artery pressure (Pap). Group 1 included 61 patients without initial pulmonary arterial hypertension (PAH), Pap being less than 20 mmHg; the average delay between the 2 catheterizations was 93.4 +/- 26.8 months. Group 2 included 32 patients with initial PAH (Pap greater than or equal to 20 mmHg), and the average delay was 85.0 +/- 26.0 months. The changes in Pap were small. They ranged from 15.5 +/- 2.4 to 19.6 +/- 7.0 mmHg in Group 1 (p less than 0.001) and from 25.8 +/- 5.6 to 27.8 +/- 9.5 mmHg in Group 2 (NS). The average increase in Pap was 0.65 mmHg/yr in Group 1 and 0.39 mmHg/yr in Group 2 (no statistical difference between the 2 groups). The other hemodynamic parameters (pulmonary capillary wedge pressure, right ventricle filling pressure, cardiac output) did not change. Hemodynamic "worsening," which was defined by an increase in Pap by greater than or equal to 5 mm Hg, was observed in 29% of the patients (n = 27). In these patients, there was a marked worsening of hypoxemia, which was not observed in the remaining 66 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Night-to-night consistency of apneas during sleep.

Abstract: The consistency of apneas from night to night was examined in 2 groups of patients. The first group had more than 100 apneas per night (frequent apnea) and the second group had less than 100 apneas per night (infrequent apnea). All patients underwent clinical polysomnography for 2 nights, with no significant weight change or treatment occurring between recordings. The frequent apnea group showed a consistent number of apneas on the 2 nights (r = 0.92, p less than 0.01), whereas the infrequent apnea group showed a highly variable number of apneas (r = 0.35, p greater than 0.10). The correlations on apnea index (apneas per hours of sleep) showed a similar result. Apnea duration and type were consistent in both groups of patients.

Airway hyperresponsiveness and changes in cell counts in bronchoalveolar lavage after ozone exposure in dogs.

Abstract: We studied whether airway hyperresponsiveness induced by ozone exposure is associated with changes in the numbers of different types of cells in bronchoalveolar lavage in dogs. Airway responsiveness to acetylcholine and the numbers of cells in lavage fluid were determined 1 wk before and then 1 h and 1 wk after 2-h exposures to filtered air and to ozone (3.0 ppm) in each of 5 dogs. Airway responsiveness and the numbers of cells in lavage fluid did not change after exposure to filtered air. By contrast, airway responsiveness increased markedly 1 h after exposure to ozone and returned to control levels 1 wk later. In addition, the numbers of neutrophils and of ciliated epithelial cells in lavage increased markedly 1 h after ozone and returned to control levels 1 wk later. Our previous study showed that airway hyperresponsiveness induced by ozone is associated with an influx of neutrophils into the most central airways (1); the present results suggest that the hyperresponsiveness is also accompanied by an influx of neutrophils into more distal airways and by desquamation of airway epithelial cells.

Selective reduction of genioglossal muscle activity by alcohol in normal human subjects.

Abstract: We recorded ventilation and genioglossal electromyographic activity in 12 awake, normal subjects before and after they drank 1 ml of ethyl alcohol per kg of body weight. Measurements were made during quiet room air breathing and during hypercapnic rebreathing. Alcohol did not alter minute ventilation, the pattern of breathing, or the ventilatory response to CO2, but it significantly reduced genioglossal activity in both quiet breathing and hypercapnia. The effect was more consistent in male than in female subjects. These results indicate that the neural mechanisms underlying the respiratory activity of the genioglossus are more susceptible to depression by alcohol than those serving the muscles of the ventilatory pump. This susceptibility may be important in the exacerbation by alcohol of obstructive apnea during sleep.

Acid-fast bacilli in sputum smears of patients with pulmonary tuberculosis. Prevalence and significance of negative smears pretreatment and positive smears post-treatment.

Abstract: We studied 977 patients with culture-proved pulmonary tuberculosis retrospectively to determine the frequency with which patients were sputum smear negative but culture positive (S-C+) prior to treatment, the frequency with which patients developed the smear positive but culture negative (S+C-) status during treatment, and the implication of these 2 phenomena to the success of treatment. One fourth (25.6%) of the patients were repeatedly S-C+ prior to treatment; the frequency of this phenomenon was inversely proportional to the extent of disease and the presence of cavities. Patients who were S-C+ prior to treatment, and whose organisms were drug-sensitive, had the fastest sputum culture conversion rate. Patients who were S+C+ without far-advanced cavitary disease had a significantly slower conversion rate after 1 month of treatment, and those with far-advanced cavitary disease had the slowest conversion rate. Patients with drug-resistant organisms had slower conversion rates than did their counterparts with drug-sensitive organisms, but in all but 4 of these, sputum smears and cultures ultimately converted to negative. The S+C- phenomenon was observed in 20.4% of patients; its frequency was related to the extent of disease and to treatment regimens that contained rifampin. In all patients who exhibited the S+C- phenomenon, sputum smears converted to negative with continuation of the same treatment regimen.