Showing papers in "The American review of respiratory disease in 1987"

Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study.

Abstract: To investigate the relationship between lung anatomy and pulmonary mechanics in acute respiratory failure (ARF), 20 patients with ARF underwent computerized tomography (CT) at 3 levels of positive end-expiratory pressure (PEEP) (5, 10, and 15 cm H2O). The static pressure-volume curve of the total respiratory system and the lung volumes (helium dilution method) were also measured. By knowing the lung volumes and analyzing the CT number frequency distribution, a quantitative estimate of normally aerated, poorly aerated, and nonaerated lung tissue was obtained at each level of PEEP. The recruitment was defined as the percent increase of normally aerated tissue from 5 to 15 cm H2O. We found that the different compliances (starting compliance, inflation compliance, and deflation compliance) were correlated only with the amount of normally aerated tissue present in the range of pressures explored by a given compliance (5 cm H2O for starting compliance and 15 cm H2O for inflation and deflation compliances). No relationship was found between the compliances and the poorly aerated and nonaerated tissue. The specific compliance was in the normal range, whereas the amount of recruitment was related to the ratio of inflation compliance to starting compliance. Our data suggest that (1) the pressure-volume curve parameters in ARF investigate only the residual healthy zones of the lung and do not directly estimate the "amount" of disease (poorly or nonaerated tissue), (2) the pressure-volume curve may allow an estimate of the anatomic recruitment, and (3) the residual normally aerated zones of the ARF lung seem to maintain a normal intrinsic elasticity.

Epidemiology of Infection by Nontuberculous Mycobacteria

Abstract: Organisms of the Mycobacterium avium, M. intracellular, and M. scrofulaceum (MAIS) group were recovered in significant numbers from 63 soil samples collected from the floodplains of 4 major rivers in the eastern United States: Hudson (NY), James (VA), Savannah (GA, SC), and Tombigbee (AL, MS). The mean numbers of M. avium intracellulars, M. scrofulaceum, and MAIS-intermediate biovars recovered increased significantly from the Hudson to the James to the Tombigbee and Savannah soil samples, agreeing reasonably well with previous findings on MAIS distribution in eastern U.S. waters and with the geographic distribution of naval recruits reacting to PPD-B and PPD-G, which is higher in the southeastern United States. From the Savannah and Tombigbee rivers, soils were collected throughout their lengths. The number of total MAIS and biovars recovered from the different soil sites varied widely and showed no obvious trends. However, statistical analysis revealed a highly significant correlation between high number...

Health Effects and Sources of Indoor Air Pollution. Part I

Abstract: Since the early 1970s, the health effects of indoor air pollution have been investigated with increasing intensity. Consequently, a large body of literature is now available on diverse aspects of indoor air pollution: sources, concentrations, health effects, engineering, and policy. This review begins with a review of the principal pollutants found in indoor environments and their sources. Subsequently, exposure to indoor air pollutants and health effects are considered, with an emphasis on those indoor air quality problems of greatest concern at present: passive exposure to tobacco smoke, nitrogen dioxide from gas-fueled cooking stoves, formaldehyde exposure, radon daughter exposure, and the diverse health problems encountered by workers in newer sealed office buildings. The review concludes by briefly addressing assessment of indoor air quality, control technology, research needs, and clinical implications.

Analysis of dose-response curves to methacholine. An approach suitable for population studies.

Abstract: Dose-response curves to methacholine were examined in 9 normal and 10 asthmatic volunteers to determine whether the relationship between dose and response can be adequately summarized by means of a single, continuous measure that is not censored at lower levels of bronchial responsiveness. Subjects underwent a standard methacholine challenge test. There was a strong linear relationship between percent decline FEV1 and cumulative dose methacholine. We summarized each dose-response curve by the slope of a line extending from the origin to the last data point obtained. This summary dose-response slope effectively separated asthmatic from normal subjects, and there was a greater than 3,000-fold difference between the least and most responsive subjects. There was a high degree of correlation between the dose-response slope determined by the standard methacholine challenge protocol and that determined by an abbreviated protocol currently being used to examine nonspecific airway responsiveness in a large, longit...

Bronchoalveolar Cell Profiles of Asthmatic and Nonasthmatic Subjects

Abstract: Asthma is associated with increased airway responsiveness to pharmacologic agents such as methacholine. Increases in airway responsiveness after exposure to allergen or ozone are associated with increased inflammatory cells in bronchoalveolar lavage both in human and in animal studies. We studied the total and differential cell counts in 10 stable atopic asthmatics who had airway hyperresponsiveness but no clinical features of airway inflammation and 10 nonasthmatic subjects, using a conventional 100-ml lavage and a 20-ml washing. Metachromatic cell numbers and eosinophils were increased in both the lavage (p < 0.01 for metachromatic cells; p = 0.05 for eosinophils) and washing (p < 0.025 for metachromatic cells and p = 0.03 for eosinophils) compared with those in nonasthmatics. In asthmatics, metachromatic cell numbers in the lavage and washing, and total cell count and, to a lesser extent, eosinophils in lavage were significantly correlated with measurements of airway responsiveness. Major basic protein...

Tuberculosis in patients with the acquired immunodeficiency syndrome. Clinical features, response to therapy, and survival.

Abstract: Tuberculosis has been reported previously in patients with acquired immunodeficiency syndrome who are at increased risk of prior infection with Mycobacterium tuberculosis. We performed a population-based study of AIDS and tuberculosis in San Francisco using the Tuberculosis and AIDS Registries of the San Francisco Department of Public Health. Of 287 cases of tuberculosis in non-Asian-born males 15 to 60 yr of age reported from 1981 through 1985, 35 (12%) also had AIDS, including 23 American-born whites. Patients with tuberculosis and AIDS were more likely to be nonwhite and heterosexual intravenous drug users than were AIDS patients without tuberculosis. Fifty-one percent had tuberculosis diagnosed before AIDS, and 37 percent had AIDS diagnosed at least 1 month prior to the diagnosis of tuberculosis. Although the lungs were the most frequent site of tuberculosis in both AIDS and non-AIDS patients, 60% of the AIDS group had at least 1 extrapulmonary site of disease compared to 28% of the non-AIDS group (p less than 0.001). Nonsignificant tuberculin skin tests were more common in AIDS patients (14 of 23 patients tested) than in non-AIDS patients (12 of 129 patients tested; p less than 0.0001). Chest radiographs in AIDS patients showed predominantly diffuse or miliary infiltrates (60%), whereas non-AIDS patients had predominantly focal infiltrates and/or cavitation (68%). Response to antituberculosis therapy was favorable in AIDS patients, although adverse drug reactions occurred more frequently than in non-AIDS patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

The epidemiology of nontuberculous mycobacterial diseases in the United States. Results from a national survey.

Abstract: During the 2-yr period 1981-83, demographic, clinical, and laboratory information was collected for 5,469 patients from whom nontuberculous mycobacteria (NTM) had been isolated. Among the potential NTM pathogens, isolates of Mycobacterium avium complex were most frequent, followed by M. kansasii, M. fortuitum, M. scrofulaceum, and M. chelonae. Almost 90% of the isolates were obtained from respiratory specimens. Prevalence rates for NTM disease, as calculated by a diagnostic algorithm, were highest for M. avium complex (1.3/10(5)), M. fortuitum-M. chelonae (0.2/10(5)). The data suggest a changing epidemiologic picture of NTM disease due perhaps to the decreasing incidence of tuberculosis, the increasing prevalence of chronic lung disease, and increased culturing of diagnostic specimens, as well as possibly a change in the ecology of these organisms.

Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation : an experimental study

Abstract: We explored the pulmonary effects of continuous mechanical ventilation (MV) at a peak inspiratory pressure of 50 cm H2O in healthy, paralyzed, and anesthetized adult sheep during a period of 48 h. The 9 control sheep (Group A) were ventilated with 40% oxygen at a tidal volume of about 10 ml/kg and a peak inspiratory pressure of 15 to 20 cm H2O. All these animals remained stable throughout the 48 h of MV with no change in lung function. The 7 sheep in Group B were ventilated with 40% oxygen using a pressure-controlled ventilator at 50 cm H2O peak inspiratory pressure, at a VT of 50 to 70 ml/kg. All sheep in Group B developed severe respiratory failure and died or were killed within 2 to 35 h, and showed parenchymal consolidation at autopsy. The 9 sheep in Group C were ventilated as in Group B, except that 3.8% CO2 was added to the inspired gases: the Group C animals deteriorated more slowly, with little change in PaO2 but with a severely reduced FRC, VT, total static lung compliance, and grossly abnormal lungs at autopsy. We conclude that in this model, mechanical ventilation at peak airway pressure of 50 cm H2O will lead to progressive impairment in pulmonary mechanics, lung function, acute respiratory failure, and alveolar cellular dysfunction, as demonstrated by highly abnormal minimal surface tension values of saline lung lavage fluid in both study groups.

Metabolism and Turnover of Lung Surfactant

Abstract: Despite the grave difficulties that beset researchers who are trying to isolate and characterize the various intracellular and extracellular forms of lung surfactant; despite the serious ambiguities of interpretation of experimental data caused by the multicomponent nature of the surfactant; despite the inaccessibility for diagnostic purposes of this material, which functions deep in the lungs; despite the fact that incisive methods of protein chemistry and molecular biology have only recently been brought to bear on lung surfactant; despite all these problems, our knowledge and understanding of lung surfactant are rapidly increasing. We know now that it is a dynamic system with many parts, and that the reserves of these are normally not large and are recycled. We believe that tight metabolic control must exist to maintain these reserves, and we already have experimental techniques to raise or lower the reserves. Heroic methods of surfactant substitution are now being tested in patients whose deficiency or risk thereof is sufficiently desperate, and the results of these clinical trials, if they are carefully documented with lung function data, will add a new dimension to our knowledge of surfactant dynamics. We may expect in the future that more subtle alterations in surfactant function will become detectable and more sophisticated methods to manipulate the system will be invented. Essential to these will be a deeper understanding of surfactant forms, pathways, kinetics, and controls. Fortunately, research on surfactant structure, metabolism, and turnover intrigues many investigators. They, we may hope, will soon provide the necessary information.

Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation.

Abstract: The local mechanisms that result in the cellular inflammation and bronchial airway hyperreactivity that characterize allergic bronchial asthma are poorly defined. In order to study these processes, we developed a method for local allergen challenge using a fiberoptic bronchoscope and direct observation and bronchoalveolar lavage (BAL) to assess the airway responses to allergen. In these studies, 11 allergic asthmatics (all of whom had previously demonstrated a late-phase asthmatic response to aeroallergen challenge) and 6 healthy, asymptomatic subjects volunteered to undergo bronchoalveolar lavage after local airway challenge via a bronchoscope wedged into subsegmental airways. These studies revealed that asthmatic airways respond to allergen with an immediate pallor followed by reactive hyperemia, edema, and bronchial narrowing. This site and a control site were relavaged at 48 or 96 h after the immediate response. Neutrophils and eosinophils increased significantly at 48 h after challenge, as did helper T-lymphocytes. Characteristically, at 96 h, neutrophil counts returned to normal values, whereas eosinophiles and helper T-cells remained elevated. Peroxidase-staining cells were also elevated at 48 h after local allergen challenge. Electron microscopy revealed degranulation of mast cells and eosinophils, both immediately and later (48 and 96 h) after local allergen challenge. Macrophages were highly activated and had phagocytized, partially intact granules from both eosinophils and mast cells. There was a significant correlation (p less than 0.001) between the concentration of allergen required to produce a visible airway response and a positive end-point skin titration in the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Neutrophilia during Late Asthmatic Reactions Induced by Toluene Diisocyanate

Abstract: The mechanism by which late asthmatic reactions are induced by toluene diisocyanate (TDI), a low molecular weight chemical that causes occupational asthma in exposed subjects, is unknown. We investigated whether early and late asthmatic reactions induced by TDI are associated with changes in airway responsiveness to methacholine and airway inflammation as determined by bronchoalveolar lavage. We measured FEV1 before and at regular intervals after exposure to TDI, and performed dose-response curves to methacholine and bronchoalveolar lavage at 8 h after TDI in a group of 6 subjects with late asthmatic reactions and in 6 subjects with only early asthmatic reactions. The same procedure was followed 2 h after TDI in a group of 6 subjects with previously documented late asthmatic reactions and in a group of 6 subjects without any previously documented asthmatic reaction after TDI. In subjects with late asthmatic reactions, neutrophils were increased at both 2 and 8 h, and eosinophils and airway responsiveness ...

The Effects of Ventilatory Pattern on Hyperinflation, Airway Pressures, and Circulation in Mechanical Ventilation of Patients with Severe Air-Flow Obstruction

Abstract: Patients with severe air-flow obstruction receiving mechanical ventilation are at risk of inadvertent pulmonary hyperinflation with morbidity and mortality caused by pneumothorax and circulatory depression. Nine patients with severe air-flow obstruction (5 asthma, 4 chronic air-flow obstruction) requiring mechanical ventilation were studied while sedated and therapeutically paralyzed. Pulmonary hyperinflation during steady-state ventilation was quantified by measuring total exhaled volume during 20- to 40-s apnea (end-inspiratory lung volume, VEI). Patients were studied at 3 levels of minute ventilation (VE) (10, 16, and 26 L/min) and at each VE, 3 levels of tidal volume (VT) (0.6, 1.0, and 1.6 L) and 3 levels of inspiratory flow (VI) (40, 70, and 100 L/min for VT = 1.0 L). There were progressive increases in VEI when VT was increased or when expiratory time (TE) was decreased either by an increase in rate (and hence VE) or by a decrease in VI (at a constant VE) reaching lung volumes as high as 3.6 +/- 0.4 L above FRC. Alveolar, central venous, and esophageal pressure rose in parallel with lung volumes, and hypotension was seen in most patients at highest lung volumes. Peak airway pressure (Ppk) was predominantly related to inspiratory flow and did not reflect changes in lung volume. Levels of ventilation required for normocapnia prior to paralysis (15.7 +/- 2.3 L/min) were associated with hypotension in 7 patients and probable hyperinflation in excess of 1.96 +/- 0.17 L above FRC. VEI is a simple, reproducible measurement of pulmonary hyperinflation and may be more important than Ppk in the causation of barotrauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory bronchiolitis causing interstitial lung disease. A clinicopathologic study of six cases.

Abstract: We describe 6 patients with chronic interstitial lung disease in whom open lung biopsies showed respiratory bronchiolitis. The patients ranged from 28 to 46 yr of age (mean, 36 yr) and included 5 men and 1 woman. All were heavy cigarette smokers. Five had respiratory symptoms, most commonly cough and dyspnea. Diffuse interstitial infiltrates were seen on chest radiographs in 5 and bibasilar atelectasis in 1. Pulmonary function tests showed mild to moderate restriction in 4 and decreased diffusing capacity in 4. The initial pathologic interpretation in 3 patients suggested a variant of idiopathic pulmonary fibrosis, and these patients received corticosteroids because of this diagnosis. All patients have remained stable or improved after a mean follow-up of 3.2 yr. Respiratory bronchiolitis should be recognized as an uncommon cause of chronic interstitial lung disease. It must be separated from the other diseases in this category because of marked differences in treatment and prognosis.

Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.

Abstract: Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Fluid balance and the adult respiratory distress syndrome

Abstract: This study examined the effect of fluid balance on survival in ARDS. Of the 213 patients entered into a prospective data collection study, we evaluated 113 patients who met strict criteria for ARDS. Multiple variables were analyzed for as long as 14 days after intubation including cardiac output, pulmonary capillary wedge pressure, mean blood pressure, intake minus output (I-O), cumulative intake minus output (cum I-O), and change in weight (Δwt). We found significant differences in cum I-O and Δwt between survivors and nonsurvivors on almost every day. Survivors lost weight and had a significantly lower cum I-O compared with nonsurvivors. Logistic regression was used to determine if Δwt and cum I-O could predict survival. Patients who lost 3 kg or more weight had a much higher survival than did those who gained 3 kg or more weight (67 and 0%, respectively, on Day 14). Similiar results were obtained using comparably low and high values for cum I-O. The logistic regression equations demonstrated that weigh...

Characterization of the lower respiratory tract inflammation of nonsmoking individuals with interstitial lung disease associated with chronic inhalation of inorganic dusts.

Abstract: The pneumoconioses, interstitial lung disorders resulting from the inhalation of inorganic dusts, are associated with chronic inflammatory processes in the lower respiratory tract. To characterize these inflammatory processes in relation to the pathogenesis of these disorders, we studied 39 nonsmoking individuals with long-term occupational exposures to inorganic dust and functional evidence of interstitial disease (asbestosis, n = 18; coal workers' pneumoconiosis, n = 15; silicosis, n = 6). In all 3 disorders, the inflammation was dominated by alveolar macrophages. Because a common feature of these interstitial lung diseases is concurrent injury and fibrosis of alveolar walls, we assessed whether these alveolar macrophages were spontaneously releasing mediators capable of giving rise to these changes. Alveolar macrophages from the study population were spontaneously releasing increased amounts of superoxide anion and hydrogen peroxide (both p < 0.01 compared to normals), oxidants capable of injuring lung...

Bradykinin-induced bronchoconstriction in humans. Mode of action.

Abstract: The effect of bradykinin was studied by inhalation in normal and asthmatic human subjects, as well as on human bronchial smooth muscle in vitro. Bradykinin caused cough and retrosternal discomfort in all subjects and bronchoconstriction in asthmatic subjects. Bradykinin was approximately 10 times more potent than histamine and methacholine, and there was a significant correlation between the subjects' sensitivity to histamine and bradykinin. Bradykinin-induced bronchoconstriction was prolonged when compared with that of histamine and the C-fiber stimulant capsaicin. This bronchoconstriction was subject to tachyphylaxis, which was also associated with desensitization of the subjects to inhaled histamine. The provocative dose causing a 35% fall in specific airway conductance (PD35) was unaffected by aspirin (1 g orally). However, ipratropium bromide (0.25 mg by nebulizer) significantly inhibited the effect of bradykinin, the PD35 being 0.8 mumol (range, 0.16 to 3.4) and 0.15 mumol (range, 0.047 to 1.15) after active dose and placebo, respectively (p less than 0.05). Likewise, cromolyn sodium (40 mg dry powder) also significantly reduced response to bradykinin, with a PD35 of 0.04 mumol (range, 0.13 to 0.31) after placebo and 0.39 mumol (range, 0.05 to 4.45) after SCG (p less than 0.05). Bradykinin only weakly constricted human bronchial smooth muscle in vitro. Bradykinin at 10(-4) caused only 21.5 +/- 5.5% of the maximal carbamylcholine contraction in 11 of 18 airways. Captopril did not enhance the effect of bradykinin. Bradykinin is a potent bronchoconstrictor of human airways in vivo, acting in part through cholinergic mechanisms but not because of the formation of prostaglandins.

Improved Efficacy of Spontaneous Breathing with Inspiratory Pressure Support

Abstract: During inspiratory pressure support (IPS) ventilation, first a negative airway pressure is produced by the patient to open a demand valve and then a constant positive airway pressure is maintained at a preset level while the patient inhales. The aim of this study was to assess the ability of 10 cm H2O IPS to improve the efficacy of spontaneous ventilation. We studied 8 intubated patients recovering from acute respiratory failure, all were breathing spontaneously via 3 different systems: (1) a Servo 900 C ventilator (SVC) without IPS, (2) a Servo 900 C ventilator with 10 cm H2O IPS, and (3) a continuous flow system (CFS). Compared with the CFS, breathing with the SVC without IPS resulted in an increased respiratory rate (RR), increased tidal Volume (Vt), increased transdiaphragmatic pressure (Pdi), and no significant change in PaO2 or PaCO2. Ventilation with IPS resulted in significant improvements in Vt, PaO2, and PaCO2 with a decreased RR and Pdi when compared with both the other modes of spontaneous ven...

Treatment of respiratory failure during sleep in patients with neuromuscular disease. Positive-pressure ventilation through a nose mask.

Abstract: Severe nocturnal hypoxemia may occur in patients with respiratory muscle weakness caused by neuromuscular disorders. Negative pressure ventilators may be partially effective in these patients but can cause upper airway obstructive apneas. We examined the effectiveness of positive pressure ventilation through a nose mask in preventing nocturnal hypoxemia and compared it with negative pressure systems. We reasoned that nasal positive pressure would provide stability for the upper airway. Five patients with neuromuscular disorders underwent a series of all-night sleep studies under control conditions, negative pressure ventilation, and positive pressure ventilation through a comfortable nose mask. Sleep staging and respiratory variables were monitored during all studies. Daytime awake lung function, respiratory muscle strength, and arterial blood gases were also measured. The severe hypoxemia and hypercapnia that occurred under control conditions were prevented by positive pressure ventilation through a nose mask. Negative pressure ventilation improved NREM ventilation in all patients, but did not prevent severe oxyhemoglobin desaturation, which occurred during REM sleep. Negative pressure ventilation appears to contribute to upper airways obstruction during REM sleep as evidenced by cessation of air flow, reduced chest wall movements, falls in arterial oxyhemoglobin saturation, and hypercapnia. With treatment, daytime PaO2 improved from a mean of 70 to 83 mm Hg, and PaCO2 decreased from a mean of 61 to 46 mm Hg. We conclude that nasally applied positive pressure ventilation is a highly effective method of providing nocturnal assisted ventilation because it stabilizes the oropharyngeal airway.

Diagnosis of nosocomial pneumonia in intubated, intensive care unit patients.

Abstract: The clinical distinction between bacterial colonization of the tracheobronchial tree and nosocomial pneumonia is difficult, especially in intubated patients We studied 51 intubated, intensive care unit patients prospectively by serial examinations of tracheal aspirates for elastin fibers, graded Gram's stains, and quantitative bacterial cultures in conjunction with clinical and radiologic observations in an attempt to develop criteria for the early detection of pulmonary infection Patients with infection had new or progressive pulmonary infiltrates plus 1 of the following: positive blood culture results, radiographic evidence of cavitation, or histologic evidence of pneumonia, or 2 or more of the following: new fever, new leukocytosis, or grossly purulent tracheal aspirates Twenty-one patients developed infection, 22 remained colonized, and 8 had an uncertain status Infiltrates developed in 34 patients (21 infected, 8 colonized, 5 uncertain status) Gram-negative bacilli were most commonly isolated and were more frequent in infected patients (81 versus 47%, p less than 005); Pseudomonas aeruginosa and Serratia marcescens were most often associated with infection No differences were observed between infected and colonized patients in demographic features, smoking history, underlying disease, previous antibiotic therapy, days in hospital before intubation, preexisting pneumonia upon intubation, or highest temperature or leukocyte count during course By univariate analysis, infected patients had a longer duration of intubation (p less than 005), higher Gram's stain grading for neutrophils (p less than 005) or bacteria (p less than 0005), higher bacterial colony counts (p less than 005), and more frequent detection of elastin fibers in tracheal aspirates (p less than 002)(ABSTRACT TRUNCATED AT 250 WORDS)

Cold facial stimulation reduces breathlessness induced in normal subjects.

Abstract: Patients with breathlessness commonly describe subjective relief when seated near an open window or in front of a fan. Previous studies suggest that a flow of air or application of cold solutions to the face, nasal mucosa, or pharynx may alter ventilation. We hypothesized that a flow of cold air directed against the cheek would reduce the sensation of breathlessness associated with loaded breathing. Sixteen subjects breathed on a device with an inspiratory resistive load (63 cm H2O/L/s) while PCO2 was maintained at 55 torr for 5 min. All studies were performed 4 times with each subject, twice with cold air directed against the cheek (4 degrees to 10 degrees C, 4 km/h) and twice with no flow on the subject. Subjects were asked to rate their breathlessness using a modified Borg scale. Cold air directed on the face reduced breathlessness induced by an inspiratory resistive load and hypercapnia (6.2 +/- 1.7 Borg scale units with no flow, 5.1 +/- 1.7 with cold air; p less than 0.002) without causing a significant reduction in ventilation. This effect was not observed when cold air was directed to the leg and does not appear to be associated with a reduction in the ventilatory response to hypercapnia or with initiation of the diving reflex. We conclude that cold air directed against the cheek significantly reduces dyspnea associated with the combination of hypercapnia and an inspiratory resistive load.

Neutrophil-mediated pulmonary vascular injury. Synergistic effect of trace amounts of lipopolysaccharide and neutrophil stimuli on vascular permeability and neutrophil sequestration in the lung.

Abstract: The pathogenesis of acute lung injury in humans is obscure, but lipopolysaccharide (LPS), complement activation, and neutrophils have been implicated. We investigated in rabbits the interaction of small amounts of intravascularly administered LPS (100 ng) with neutrophil chemotactic factors, the synthetic chemotactic peptide formyl-norleucyl-leucyl-phenylalanine (FNLP), and the biologically relevant chemotactic fragments of C5 (C5f). These neutrophil stimuli produce neutropenia when injected intravascularly in rabbits, reflecting neutrophil adherence to vascular endothelium. When LPS was injected with FNLP, the duration of neutropenia was enhanced. Studies with radiolabeled neutrophils infused in vivo demonstrated prolonged neutrophil sequestration within the lung in rabbits that were given FNLP plus LPS, an effect that was visible for 4 h after injection. Morphometric analysis of tissue sections 4 h after infusion confirmed the presence of greater numbers of neutrophils in the lungs of animals receiving LPS and FNLP. When a combination of LPS and chemotactic factors was infused at both zero and 6 h, we found a marked enhancement of lung vascular permeability at 24 h (as assessed by radiolabeled albumin accumulation), an effect not seen with either LPS or chemotactic factor alone. Ultrastructural studies revealed neutrophil sequestration and alteration in endothelial cells in the animals that received the combination of LPS and chemotactic factors. Neutrophil depletion with nitrogen mustard completely abolished the increased vascular permeability seen in animals that received LPS and chemotactic factors. This study suggests that small amounts of intravascularly administered LPS enhance the sequestration of neutrophils within the lung and increase lung vascular permeability and endothelial injury caused by neutrophils stimulated by intravascularly administered chemotactic factors. This mechanism may be relevant to the production of acute lung injury in human beings.

Quantitative deposition of aerosolized gentamicin in cystic fibrosis.

Abstract: In cystic fibrosis (CF), the clinical effectiveness of aerosolized antibiotics is controversial. Previous investigators have not considered the type of nebulizer, droplet size, and dose to the lung in assessing the results of aerosol therapy. The present study tests the importance of these factors by standardizing an aerosol system for delivery of antibiotics and other agents to patients with CF. Particle size, distribution, and output from a commercially available nebulizer were measured. Thirteen patients with CF inhaled aerosol (MMAD = 1.1 micron) containing gentamicin (160 mg in nebulizer) and 99mTc-labeled human serum albumin. Patients' sputum and serum were analyzed for gentamicin levels by immunoenzymatic assay (Emit; Syva Corp., Palo Alto, CA). Using a gamma camera and suitable filters, central versus peripheral deposition (C/P ratio) and whole lung deposition were measured and related to sputum gentamicin levels. Gentamicin deposit averaged 12.3 mg +/- 5.9 (SD) or 7.69% of the original amount placed in the nebulizer. Peak sputum levels averaged 376.6 micrograms/ml +/- 275, whereas serum levels were undetectable in all patients. When peak sputum levels were normalized for the amount deposited, a close correlation with C/P ratio was obtained (r = 0.88, p less than 0.05). Furthermore, an inverse relationship was found between the C/P ratio and the %FEV1 (r = 0.76, p less than 0.05). Finally, a bell-shaped relationship between deposited dose and minute ventilation was seen in the patients (r = 0.88, p less than 0.05), i.e., an optimal minute ventilation was shown. These relationships may be important when designing future clinical studies.

High resolution computed tomography of inflation-fixed lungs. Pathologic-radiologic correlation of centrilobular emphysema.

Abstract: Centrllobular emphysema (CLE) is a disease defined pathologically. Assessment of the accuracy of high resolution computed tomography (CT) in the diagnosis of centrilobular emphysema has been hampered by a lack of pathologic correlation. We applied high resolution computed tomography to 20 postmortem lung specimens fixed by a method that allows for direct one-to-one pathologic-radiologic correlation. The degree of centrilobuler emphysema was assessed radiologically on a visual grading system based on nonperipheral low-attenuation areas. The lungs were then sectioned along the plane of the CT image, and the degree of centrilobular emphysema was graded pathologically by scoring against a panel of standards. A significant correlation (r = 0.91, p < 0.005) was found between the pathologic grade and the in vitro CT score.