Showing papers in "The American review of respiratory disease in 1985"

Damage of the airway epithelium and bronchial reactivity in patients with asthma.

Abstract: We measured bronchial reactivity to inhaled histamine and prepared electron micrographs from bronchial biopsies from 8 asthmatic patients who never smoked (2 females, 6 males, 18 to 62 yr of age). Judging from their clinical histories and the need for medication and long-term follow-up of PEF values, 2 of them had mild asthma, 3 moderately severe, and 3 severe asthma. They had not experienced respiratory infections for at least 2 months prior to the study. The result, obtained from the cumulative dose-response curve, was expressed as the provocative dose (PD20) of histamine producing a 20% fall in forced expiratory volume in one second (FEV1). In 5 patients, the PD20 varied from 0.049 mg to 2.234 mg. In the sixth patient, only PD15 could be measured (5.187 mg). In 2 patients, the low initial FEV1 values, because of severe, partly irreversible obstruction, prevented the measurement of bronchial reactivity. Bronchial biopsies were taken with rigid tube bronchoscopy from 3 levels: (1) at the carina of the right upper lobe, (2) at the opening of the right middle or lower lobe, and (3) inside the right lower lobe. The specimens were prepared for both light and electron microscopy. Fresh biopsies showed that asthma patients can have epithelial destruction at all levels of the airways. The ciliated cells appeared to be the most destroyed cell type in the epithelium. Intraepithelial nerves and mast cells were seen. Epithelial destruction in the respiratory tract of the asthma patients with mild to severe bronchial hyperresponsiveness was prominent enough to expose the epithelial nerves for specific or nonspecific stimuli.

Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions.

Abstract: In order to obtain information about the nature of the local inflammatory process during late asthmatic reactions after house dust mite inhalation, bronchoalveolar lavage (BAL) was performed in 19 asthmatic patients and in 5 control subjects. In 16 of the patients and in all of the control subjects, BAL was performed 6 to 7 h after allergen inhalation. Six of the patients showed early and late asthmatic reactions (LAR), 5 showed early reactions, and 5 showed no reactions. Bronchoalveolar lavage was also performed shortly after the early reaction in 5 patients with documented combined early and late reactions. In the BAL fluid of the patients with LAR, a significant eosinophilia (0.01 less than p less than 0.05) was found compared with that in all other patient groups and with that in the control subjects. This bronchoalveolar eosinophilia was accompanied by elevated eosinophil cationic protein/albumin ratio in the BAL fluid (0.01 less than p less than 0.05). These observations suggest that eosinophils and their mediators might be involved in the development of LAR after allergen inhalation.

Causes of mortality in patients with the adult respiratory distress syndrome.

Abstract: This study analyzed the factors causing and contributing to death in patients with the adult respiratory distress syndrome (ARDS). Two hundred seven patients were prospectively identified as being at risk for development of ARDS. Forty-seven patients developed ARDS, and the remaining 160 patients were used as a comparison control group. The severity of dysfunction in 8 organ systems and the presence of sepsis syndrome were determined by chart review after discharge or death. Sepsis syndrome was specifically defined by signs and laboratory tests reflecting infection or inflammation plus evidence of a deleterious systemic effect (hypotension, reduced systemic vascular resistance, or unexplained metabolic acidosis). Mortality was 68% in the ARDS group compared to 34% in the control group (p less than 0.005). Only 16% (5 of 32) of deaths in the ARDS group were from irreversible respiratory failure. Most deaths in the first 3 days after entry into the study could be attributed to the underlying illness or injury. The majority of late deaths were related to sepsis syndrome. Of the 22 patients with ARDS who died after 3 days, 16 (73%) met our criteria for sepsis syndrome. There was a sixfold increase in sepsis syndrome after ARDS compared with that in the control group (p less than 0.001). When sepsis syndrome preceded the ARDS, the abdomen was the predominant source, but when sepsis syndrome occurred after the onset of ARDS there was usually a pulmonary source. Our findings indicate that sepsis syndrome, rather than respiratory failure, is the leading cause of death in patients with ARDS.

Normal standards for an incremental progressive cycle ergometer test.

Abstract: One hundred healthy subjects (50 male and 50 female), selected to provide an even distribution of age (15 to 71 yr) and height (165 to 194 cm in males and 152 to 176 cm in females), underwent a progressively incremental (100 kpm/min each min) exercise test to a symptom-limited maximum. Measurements were made of O2 intake and CO2 output, ventilation and breathing pattern, heart rate and blood pressure, and rating of perceived exertion. The ventilatory anaerobic threshold was identified. Predictive data were derived for measurements at maximal and submaximal exercise. Maximal power output (Wmax) and oxygen intake (VO2max) varied with sex (0, male; 1, female), age (yr), and height (Ht, cm): Wmax = 20.4 (Ht) - 8.74 (Age) - 288 (Sex) - 1,909 kpm/min (SEE, 216; r, 0.858); VO2max = 0.046 (Ht) - 0.021 (Age) - 0.62 (Sex) - 4.31 L/min (SEE, 0.458; r, 0.869). The extent of leisure time activity exerted a positive influence on VO2max (r, 0.47; p less than 0.001); VO2max was also related to lean thigh volume (r, 0.79). Maximal heart rate (HR) declined as a function of age: HRmax = 202 - 0.72 (Age) beats/min (SEE, 10.3; r, 0.72). Maximal O2 pulse (O2Pmax) was related to height and was systematically higher in males than in females: O2Pmax = 0.28 (Ht) - 3.3 (Sex) - 26.7 ml/beat (SEE, 2.8; r, 0.86). Ventilation was closely related to CO2 output, and the maximal tidal volume was related to vital capacity. The VO2 increased linearly with power throughout the test; in an individual subject, the intercept of this relationship was positively influenced by weight and height.(ABSTRACT TRUNCATED AT 250 WORDS)

Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis.

Abstract: Many studies have been carried out in the past 10 yr dealing with the possible role of elastase in the pathogenesis of pulmonary emphysema. These include newer observations in animal models revealing augmentation of elastase-induced lesions by lathyrogens or by exposure to cigarette smoke. In general, the animal model experiments have focussed attention on repair-processes in the lung and shown that such processes may exert a major influence on the outcome of the initial proteolytic insult. Human studies exploring correlations between elastase levels in neutrophils or serum and development of disease have provided conflicting data; however, measurement of enzymes in pulmonary secretions have yielded more suggestive results. Assessments of lung elastase inhibitors in humans continue to support the importance of alpha-1-proteinase inhibitor in the protection of the lower respiratory tract, but newer information on locally produced, low molecular weight elastase inhibitors indicates that these, too, may play a significant role. Attempts have been made to link cigarette smoking to the development of emphysema at the chemical and cellular levels. These studies have focussed on: (1) the recruitment of elastase-producing leukocytes to smokers' lungs, (2) inactivation of lung elastase-inhibitors by tobacco products or by metabolites released from tobacco-stimulated lung cells, and (3) interference with elastin neosynthesis (repair) in the smoker. Additional information is also available concerning the biochemical properties of neutrophil and macrophage elastases, although it is still unclear which of these enzymes plays the predominant role in chronic lung injury associated with smoking. Perhaps the greatest advance in the emphysema field in recent years involves new discoveries concerning the structure and function of the alpha-1-proteinase (elastase) inhibitor. Applications of recombinant DNA technology and genetic engineering have made it possible to design modified inhibitors with striking new properties. These agents may enjoy significant clinical application in the not too distant future.

Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Abstract: Sixteen patients with severe chronic obstructive pulmonary disease (COPD) (average values at the onset of O2 therapy: FEV1, 891 +/- 284 ml; PaO2, 50.2 +/- 6.6 mmHg; PaCO2, 51.0 +/- 6.4 mmHg) underwent 3 consecutive right heart catheterizations. The first was performed 47 +/- 28 months (T0) before the onset of long-term O2 therapy (LTO2). The second was performed just before the onset of LTO2 (T1). The third was performed after 31 +/- 19 months of LTO2 (T2). Oxygen therapy (15 to 18 h/day) was prescribed on the basis of usual criteria. From T0 to T1, PaO2 decreased from 59.3 +/- 9.4 to 50.2 +/- 6.6 mmHg, and mean pulmonary arterial pressure (Ppa) worsened from 23.3 +/- 6.8 to 28.0 +/- 7.4 mmHg (p less than 0.005). From T1 to T2, PaO2 was stable, whereas Ppa decreased from 28.0 +/- 7.4 to 23.9 +/- 6.6 mmHg (p less than 0.05). Pulmonary hypertension improved in 12 of the 16 patients. Before the onset of LTO2 (from T0 to T1), there was a yearly increase in Ppa of 1.47 +/- 2.3 mmHg, whereas during LTO2 a yearly decrease of 2.15 +/- 4.4 mmHg was observed, and the difference between these 2 values was highly significant. The changes in Ppa either from T0 to T1 or from T1 to T2 were not associated with concomitant changes in cardiac output or pulmonary capillary wedge pressure but were related to changes in pulmonary vascular resistance. These results suggest that LTO2 for 15 to 18 h/day can reverse the progression of pulmonary hypertension in a high percentage of patients with severe COPD, but that normalization of Ppa is rarely observed.

Lung biopsy in rheumatoid arthritis.

Abstract: Forty open lung biopsies from patients with rheumatoid arthritis and possible "rheumatoid lung disease" were reviewed in an attempt to correlate histology with radiologic, physiologic, and prognostic variables. A wide variety of histopathologic features was seen, and primary and secondary patterns of injury were recognized. Five different groups based on histologic patterns were identified: pulmonary rheumatoid nodules, usual interstitial pneumonia (UIP), bronchiolitis obliterans with patchy organizing pneumonia (BOOP), lymphoid hyperplasia, and cellular interstitial infiltrates. The finding of rheumatoid nodules as the primary pattern imparted a uniformly good prognosis, whereas the pattern of UIP indicated a poor one. Patients with BOOP had a more favorable prognosis than did patients with UIP, as did patients with lymphoid hyperplasia and/or nonspecific cellular interstitial infiltrates. Consistent correlations between pulmonary function testing and roentgenographic and histologic findings were not found. The term "rheumatoid lung disease" is of no use as a histologic diagnosis because it encompasses a broad spectrum of morphologic changes that carry significantly different prognoses.

Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome.

Abstract: Although right heart failure is a recognized complication of obstructive sleep apnea, the incidence and pathogenesis of this complication have not been established. We therefore studied 50 consecutive patients with obstructive sleep apnea to determine the incidence of right heart failure and the factors involved in its development. Six patients (12%) were found to have right heart failure. There were no differences in the number of apneas between those with right heart failure (mean ± SE, 30 ± 10 per h sleep) and those without right heart failure (33 ± 4 per h sleep). In contrast, mean nocturnal oxygen saturation was lower in patients with right heart failure (76 ± 3%) than in those without right heart failure (90 ± 1%; p < 0.001). Furthermore, patients with right heart failure also had a substantially lower awake arterial PO2 (52 ± 4 mmHg versus 75 ± 2 mmHg; p < 0.001) and a higher Pco2 (51 ± 2 mmHg versus 36 ± 1 mmHg; p < 0.001) than those without right heart failure. Severe nocturnal hypoxemia in the a...

Autoradiographic visualization of beta-adrenoceptor subtypes in human lung.

Abstract: Adrenoceptor subtypes have been localized in human lung by an autoradiographic method, using [125I]iodocyanopindolol (ICYP) to label beta-receptors in tissue sections. The ICYP was incubated with cryostat sections of microscopically normal human lung method on microscope slides for 2 h at 37 degrees C. Nonspecific binding was determined by incubating adjacent serial sections in the presence of 200 microM (-)-isoproterenol. Specific binding, which accounted for greater than 90% of total counts bound to the sections, was saturable, of high affinity, and stereoselective, having the same pharmacologic characteristics as binding to homogenates prepared from the same lungs. Competition with selective beta-receptor antagonists ICI 118,551 (beta 2-selective) and betaxolol (beta 1-selective) showed that the ratio of beta 2 to beta 1-receptors in the sections was approximately 3:1. Autoradiography revealed that beta-receptors were widely distributed, with dense labeling over airway epithelium, alveolar walls, and submucosal glands, and a lower density of grains over airway and vascular smooth muscle. The beta-receptors of airway smooth muscle from large and small airways were entirely of the beta 2-receptor subtype, which is consistent with functional studies. Similarly, beta-receptors of airway epithelium and vascular smooth muscle were also entirely of the beta 2-receptor subtype. In bronchial submucosal glands and alveolar walls, both receptor subtypes appeared to coexist with beta 2-receptors, making up 10% of the total in glands and 30% in alveoli. The significance of beta 1- and beta 2-receptors in alveolar walls (which account for greater than 90% of total beta-receptors in human lung) remains to be determined.

The radiographic appearance of tuberculosis in patients with the acquired immune deficiency syndrome (AIDS) and pre-AIDS.

Abstract: We reviewed the medical records and chest radiographs of 23 adult patients with culture-proved tuberculosis and verified acquired immune deficiency syndrome. Seventeen patients, including 8 with disseminated tuberculosis, had positive sputum or bronchial washing cultures for Mycobacterium tuberculosis. Their initial pretreatment radiographs revealed hilar and/or mediastinal adenopathy in 10 patients (59%), localized pulmonary infiltrates limited to the middle or lower lung fields in 5 patients (29%), localized pulmonary infiltrates involving an upper lobe in 3 patients (18%), diffuse miliary or interstitial infiltrates in 3 patients (18%), no pulmonary infiltrates in 6 patients (35%), and no abnormalities in 2 patients (12%). Pulmonary cavitation was not seen. Only 1 patient (6%) had a chest radiograph typical of adult onset reactivation tuberculosis (i.e., localized pulmonary infiltrate involving the upper lung fields without hilar or mediastinal adenopathy). Six patients (35%) had pulmonary infiltrates ...

Evidence for chronic inflammation as a component of the interstitial lung disease associated with progressive systemic sclerosis.

Abstract: Progressive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS have held it to be a “pure” f ibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis is associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, gallium-67 scanning, and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS is clearly associated with the presence of macrophages, lymphocytes, and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. Gallium-67 scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lav...

Measurement of static compliance of the total respiratory system in patients with acute respiratory failure during mechanical ventilation. The effect of intrinsic positive end-expiratory pressure.

Abstract: In mechanically ventilated patients with acute respiratory failure, the static compliance of the total respiratory system is conventionally obtained by dividing the tidal volume by the difference between the "plateau" pressure measured at the airway opening (PaO) during an occlusion at end-inspiration and positive end-expiratory pressure (PEEP) set by the ventilator. This analysis is valid only if the elastic recoil pressure of the respiratory system is zero at the end of expiration, indicating that the system has reached its elastic equilibrium point. To test if this is always the case, in 14 mechanically ventilated patients with acute respiratory failure, measurements were made of PaO and of flow and volume changes. In only 4 of the patients did expiratory flow become nil before end-expiration and inspiratory flow started synchronously with the onset of the positive-pressure swing delivered by the ventilator, indicating that in these 4 patients the end-expiratory elastic recoil pressure was indeed zero. By contrast, in the remaining 10 subjects, expiratory flow was still present when the ventilator had already begun to increase PaO, indicating that the end-expiratory elastic recoil pressure was not zero. Indeed, in all these 10 patients, a positive delta PaO (as much as 7.5 cm H2O) had to be applied by the ventilator before the actual onset of inspiratory flow. This delta PaO represents the pressure required to counterbalance the end-expiratory elastic recoil before inspiratory flow will begin, and can be termed intrinsic PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Neutral metalloendopeptidase in human lung tissue and cultured cells.

Abstract: The distribution of a neutral metalloendopeptidase (NEP), or “enkephalinase,” in human lung tissue and cultured cells was compared with that of angiotensin I converting enzyme (ACE). The specific activities of NEP and ACE were measured in homogenates of fetal lung tissue and in isolated airways and pulmonary vessels. NEP activity was highest in airway tissue, and ACE activity was highest in isolated vessels. Human endothelial cells from either umbilical veins or pulmonary arteries had high ACE activity (80 to 90 nmol/h/106 cells) but only a trace of NEP activity (0.5 to 0.6 nmol/h/106 cells). Fibroblasts cultured from human lungs were low in ACE but richer in NEP than cultured endothelial cells. Fibroblasts from human foreskins or caesarean section skin were the richest source of NEP activity (60 to 80 nmol/h/106 cells). Immunohistochemical studies confirmed the biochemical assays. As expected, ACE was localized on the luminal surface of blood vessels, with a distribution similar to that of factor VIII an...

Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum

Abstract: We studied sputum tobramycin concentrations after intravenous administration in 10 cystic fibrosis patients. Tobramycin concentrations were determined by a bioassay and a radioenzymatic assay (REA). The bacterial density of Pseudomonas aeruginosa in sputum was examined serially during therapy. Bioactivity of tobramycin in the sputum was low and increased little during treatment. In contrast, tobramycin content (as assayed by REA) showed a progressive accumulation of the drug to high concentrations: a mean of 82 micrograms/g sputum after 3 wk of therapy in 4 patients. Pseudomonas aeruginosa was eradicated from the sputum in 3 of 4 patients receiving antibiotic therapy for 3 wk. Eradication correlated with tobramycin sputum concentrations measured by REA, which were 20-fold greater than the apparent tobramycin inhibitory concentration. A bactericidal effect of aminoglycosides in the presence of sputum in vitro could only be reliably produced with concentrations 25-fold the MIC. We conclude that tobramycin penetrates cystic fibrosis (CF) sputum and accumulates over time. Although CF sputum antagonized the bioactivity of aminoglycosides, 3 wk of intravenous therapy combined with an antipseudomonal beta-lactam antibiotic may be effective in eradication of P. aeruginosa from sputum of certain CF patients.

Fluid loading increases oxygen consumption in septic patients with lactic acidosis.

Abstract: We prospectively evaluated 20 patients with systemic sepsis and signs of circulatory failure to determine if fluid loading was associated with increases in systemic oxygen delivery (DO2) and consumption (VO2). Fluid loading led to an increase in DO2 in 14 patients (70%). Patients who demonstrated increased DO2 with a corresponding increase in VO2 (Group A, n = 8) had significantly higher (p less than 0.05) initial blood lactate levels (4.9 +/- 2.9 mmol/L, mean +/- SD) than did patients without an increase in VO2 (Group B, n = 6, 1.9 +/- 1.0 mmol/L). A decrease in DO2 that was attributed to hemodilution was noted in the remaining 6 patients (Group C). Group C exhibited elevated lactate levels (5.1 +/- 2.4 mmol/L) and no significant changes in VO2. We conclude that lactic acidosis, a marker of anaerobic metabolism, predicts increases in VO2 in septic patients who respond to fluid loading with an increase in DO2.

Adult respiratory distress syndrome. Prognosis after onset.

Abstract: In 88 patients with the adult respiratory distress syndrome, clinical, laboratory, cardiopulmonary, and demographic data collected on the day of onset of the syndrome were used to identify predictors of survivorship and mortality. Variables that individually were associated with mortality were then analyzed simultaneously by the Cox proportional hazards function and by multiple discriminant function using a step-up procedure. Four variables taken singly were significantly associated with mortality. These were the presence of less than 10% band forms on the initial peripheral blood smear, persistent acidemia with arterial pH less than 7.40, calculated HCO-3 less than 20 mg/dl, and blood urea nitrogen greater than 65 mg/dl. After eliminating those variables that did not contribute significantly to mortality in the presence of the others, only low band forms, low pH, and low HCO-3 were significantly associated with increased mortality. These findings illustrate the continued high mortality rate in the syndrome and indicate possible systemic aberrations that contribute to its severity.

Distribution of forced expiratory volume in one second and forced vital capacity in healthy, white, adult never-smokers in six U.S. cities.

Abstract: As part of a longitudinal study of the respiratory health effects of air pollution, we measured the lung function of 2,454 white adults 25 to 74 yr of age who had never smoked and who reported no respiratory symptoms These measurements were analyzed to develop a simple model for the cross-sectional dependence of pulmonary function on height, sex, and age Both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) can be effectively standardized for body size by dividing each pulmonary function measurement by the square of the standing height (HT2) The age-specific distribution of these standardized measurements is approximately Gaussian, with variance that is independent of age Plots of FEV1/HT2 and FVC/HT2 against age showed a nonlinear relationship consistent with an increase in the rate of pulmonary function loss with age On the basis of these graphic analyses, both pulmonary function measurements were fitted to a four-parameter normative model including sex and linear and quadratic terms in age as dependent variables This model gave predictions that were very close to those from more complicated models currently in use Predicted percentile levels were calculated for each sex and age, and shown to describe the observations well The estimated annual change in height-standardized lung function based on the cross-sectional model was compared with the observed change between the first and second examinations of these adults 3 yr later The observed changes were close to predicted values, except for subjects younger than 35 yr of age at their first examination The observed change was larger for men than for women Such simple longitudinal comparisons are subject to selection bias In this study, subjects in the lowest quartile of FEV1/HT2 for their age and sex at the first examination had a lower probability of providing a lung function measurement 3 yr later

Increased numbers of hypodense eosinophils in the blood of patients with bronchial asthma.

Abstract: We investigated the density of blood eosinophils from patients with asthma using polyvinylpyrrolidone-coated silica gel (Percoll) discontinuous density gradient centrifugation of peripheral blood leukocytes. Ten patients with allergic asthma, 10 normal subjects, and 2 patients with the hypereosinophilic syndrome (HES) were studied. The density distribution profiles of eosinophils from normal subjects showed: (1) peaks at densities of 1.085 to 1.090 g/ml and (2) inflection points or nadirs near 1.082 g/ml, below which only 10% of eosinophils were found. On the basis of these results, we divided eosinophils into 2 subpopulations: normodense (> 1.082 g/ml) and hypodense (< 1.082 g/ml). Densities of eosinophils from patients with asthma and HES peaked at 1.083 and 1.076 g/ml (mean values), respectively, significantly lighter than eosinophils from normal donors (p < 0.005 and p < 0.001, respectively). The proportions of hypodense eosinophils in patients with asthma and HES were 35 and 95%, respectively, and we...

Extracellular matrix in normal and fibrotic human lungs.

Abstract: Polyclonal affinity-purified antibodies to human collagen types I, III, and IV, and laminin were used to compare the extracellular matrix (ECM) in 10 normal and 32 abnormal lungs by indirect immunofluorescence. In normal lungs, type IV collagen and laminin codistributed in a uniform linear pattern along the epithelial and endothelial basement membranes. Type III collagen was found within the alveolar septa and interstitium in an interrupted ribbonlike pattern and was aggregated at the entrance rings of the alveoli. Type I collagen was distributed irregularly within the alveolar wall and was less prominent than type III collagen. In patients with pulmonary disease not characterized by interstitial fibrosis (n = 15), the distribution of ECM components studied was essentially normal. In pulmonary disease in which interstitial fibrosis was the characteristic feature, such as idiopathic pulmonary fibrosis (IPF) and adult respiratory distress syndrome (ARDS) (n = 17), collagen types I and III accumulated in the expanded interstitium. Type III collagen was initially predominant in the thickened alveolar septa and interstitium, whereas type I collagen appeared to be the principal collagen at later stages in the disease course. The basement membrane was disrupted early in the disease course with invasion of the alveolar spaces by interstitial collagens similar in type to those present in the adjacent interstitium.

Noninvasive determination of respiratory system mechanics during mechanical ventilation for acute respiratory failure.

Abstract: In 10 acutely ill patients mechanically ventilated for management of acute respiratory failure, respiratory system mechanics were determined with the interrupter technique as described recently (J Appl Physiol 1984; 56:681–690). Flow, volume, and tracheal pressure were measured throughout a series of brief expiratory interruptions. A plateau in tracheal pressure during interruption was observed in all patients, indicating respiratory muscle relaxation as well as equilibration between alveolar and tracheal pressure. Measurement of the plateau in postinterruption tracheal pressure, corresponding volume, and preceding flow enabled determination of the passive elastic and flow-resistive properties of the total respiratory system. In general, the volume-pressure relationship was linear over the expired volume examined and did not necessarily pass through the origin, indicating deviation of the end-expiratory lung volume during mechanical ventilation from the equilibrium position of the respiratory system. Elas...

Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma

Abstract: The effect of pharmacologic agents on mast cell mediator release was investigated in vivo. Eight atopic asthmatic subjects with airways relatively unreactive to nonspecific stimuli (geometric mean PC20 methacholine, 4.0 mg/ml) underwent single-concentration allergen challenge before (control) or after inhaling albuterol 200 µg, cromolyn sodium 20 mg, or 0.9% sodium chloride placebo. Six of the same subjects also underwent allergen challenge after pretreatment with ipratropium bromide, 1 mg. Airway responses to pharmacologic agents and bronchial challenge were measured by change in both specific airway conductance (SGaw) and FEV1, Mast cell mediator release was monitored by serial change in plasma histamine and, in addition, serum neutrophil chemotactic factor (NCF) on the placebo, albuterol, and cromolyn sodium challenge days. Control and placebo allergen challenges were associated with repeatable mean maximal falls in SGaw (48.5 versus 49.6%) and FEV1 (25.7 versus 25.5%). The mean increments in plasma hi...

The relationship of respiratory infections in early childhood to the occurrence of increased levels of bronchial responsiveness and atopy.

Abstract: We assessed the relationship of antecedent acute respiratory illness to the occurrence of airway responsiveness and atopy in a population-based cohort of 194 children 12 to 16 yr of age from East Boston, Massachusetts. A history of croup or bronchiolitis as reported by their parents was determined at study onset when the children were 5 to 9 yr of age. During the second and third years of the study, acute respiratory illness was assessed. Five years after the prospective respiratory illness assessment, airway responsiveness was evaluated with eucapneic hyperpnea to subfreezing air, and atopy was evaluated with skin tests to 4 environmental antigens. Both a prior history of croup of bronchiolitis (OR = 2.29, p = 0.04) and greater than 2 acute lower respiratory illnesses (OR = 3.72, p = 0.012) were associated with increased levels of airway responsiveness. Neither index of respiratory illness experience was related to the presence of atopy. However, maternal cigarette smoking was significantly associated wi...

Endotoxin in cotton dust and respiratory function decrement among cotton workers in an experimental cardroom.

Abstract: To study the various reactions of gram-negative bacteria and their endotoxins observed in workers exposed to cotton dust, experiments were undertaken where cotton mill workers carded cottons from different geographic locations, each containing different amounts of bacterial endotoxins. Exposure was determined as the vertical elutriator dust and endotoxin levels. Measurements were made of the forced expiratory volume in one second (FEV1) and the number of blood neutrophils before and after work, and the prevalence of symptoms of byssinosis was recorded. There was a significant correlation between the vertical elutriator endotoxin levels and the group mean changes in FEV1 (p < 0.01) but no correlation between vertical elutriator dust levels and changes in FEV1. There was also a dose-response relationship between the endotoxin levels and the presence of symptoms of byssinosis in the exposed workers as well as between endotoxin levels and an increase in blood neutrophils. This observation supports findings fr...

Biochemical and pathologic evidence for proteolytic destruction of lung connective tissue in cystic fibrosis.

Abstract: The risk for proteolysis of lung connective tissue was evaluated in patients with cystic fibrosis (CF) with chronic, severe lung infections by measuring uninhibited elastase activity in sputum samples and urinary excretion of desmosines (cross-linking amino acids in elastin). Of the 16 patients included in the study, 11 were infected with Pseudomonas aeruginosa, 2 with Pseudomonas cepacia, and 2 with both P. aeruginosa and P. cepacia. Uninhibited elastase activity (0.34 to 20.2 micrograms elastin degraded/mg protein/30 min) was detected in the sputum samples from each of 13 patients tested. Serine elastase activity was detected in the sputum of each of 12 patients, and metalloelastase (P. aeruginosa elastase and possibly macrophage elastase) activity was detected in the sputum of 11 of 12 patients tested. Male patients with CF excreted significantly more elastin cross-links (desmosines) in their urine than did control male subjects (3.6 +/- 1.7 micrograms/kg/24 h versus 1.5 +/- 0.6 micrograms/kg/24 h; p less than 0.01), and there was a significant correlation (p less than 0.05) between urine desmosine excretion and the severity of lung disease in the patients with CF as indicated by chest roentgenogram score. In 3 autopsied patients, abnormal elastin fibers were seen by light microscopy in all lung compartments. Fragmented and exfoliated elastin, evidence of active elastolysis, was noted in bronchial ulcers and abscesses. The results of this study suggest that proteolytic destruction of lung connective tissue is an ongoing process in the chronically infected CF lung and that this proteolysis contributes to the pathologic changes observed in airways and alveolar parenchyma.

Loss of alveolar attachments in smokers. A morphometric correlate of lung function impairment.

Abstract: We studied post-mortem 9 nonsmokers' lungs and 9 smokers' lungs as well as 14 surgical smokers' lungs to examine the possible relationship of the number of alveolar attachments with airways inflammation and with lung function. Alveolar attachments are the alveolar walls radially attached to the small airways, and any discontinuity or rupture of these alveolar walls was considered abnormal. Normal and abnormal attachments were counted in nonsmokers and smokers and expressed as number of attachments, distance between attachments, and percentage of abnormal attachments. Although internal small airways diameter and mean linear intercept were not significantly different between smokers of either group and nonsmokers, significant differences in number of attachments (p less than 0.001), distance between attachments (p less than 0.01), and percentage of abnormal attachments (p less than 0.01) were found. The 3 indexes of alveolar attachments correlated significantly with the score for airways inflammation and with the elastic recoil pressure in smokers. No significant correlation with any other lung function test was found. We conclude that smokers have fewer alveolar attachments than do nonsmokers, and that the loss of alveolar attachments represents an early stage in the destruction of lung parenchyma, and is probably linked to inflammation of the small airways. Because of the strategic situation of this lesion, it could be responsible in part for the loss of elastic recoil seen in the initial stages of chronic obstructive pulmonary disease.

Cigarette smoking and health

Abstract: Cigarette smoking is the major preventable cause of increased mortality and premature disability in the United States. Smoking is a proven cause of coronary heart disease, chronic bronchitis and emphysema, and lung and other cancers. Maternal smoking is associated with low infant birth weight, increased perinatal mortality, and several complications of pregnancy. Passive smoking is associated with increased incidence of lower respiratory tract infections in very young children and may increase the risk of lung cancer in the nonsmoker. Smoking cessation is difficult because of nicotine addiction and psychological and social factors. Physicians and other health professions must be active both in helping people quit smoking and in preventing nonsmokers from starting. We recommend a national effort focused on preventing young people from starting to smoke.

Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma.

Abstract: We studied 40 patients with acute exacerbations of asthma to determine the efficacy of a 3-h intravenous infusion of aminophylline in patients who were already being treated with an inhaled beta-adrenergic agonist (metaproterenol). Each patient was treated with inhaled metaproterenol at hourly intervals for 3 h. In addition, patients were randomly assigned to therapy with either intravenous aminophylline or placebo. Neither the patient nor the house officers and nurses caring for the patient knew whether aminophylline or placebo was given. The FEV1 improved continually throughout the study to a similar extent in both treatment groups, but the patients treated with aminophylline had significantly more adverse effects (p less than 0.025, Mann-Whitney). There was no apparent benefit from aminophylline even in patients who presented to the emergency room with severe airway obstruction (FEV1 less than 0.8L) or with plasma theophylline levels less than 10 mg/L. We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled metaproterenol in the treatment of acute exacerbations of asthma.

The effect of inhaled leukotriene D4 in humans.

Abstract: Leukotriene D4 (LTD4) is a potent bronchoconstrictor that may play an important role in asthma. To better characterize the effect of LTD4 on human airways, normal, rhinitic, and asthmatic subjects underwent inhalation challenge tests with LTD4 and methacholine. In all subjects increasing concentrations of LTD4 produced a parallel decrease in specific airway conductance and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (). These changes occurred independent of any decrease in FEV1 or increase in functional residual capacity. The airway response to LTD4 was maximal within 2 to 3 min, persisted for approximately 30 min, and resolved over 1 to 3 h. Late effects were not seen. Rhinitic subjects were 3 to 5 times (p < 0.01) and asthmatic subjects were 25 to 100 times (p < 0.001) more sensitive than were normal subjects to LTD4. All 3 groups of subjects were 250 to 850 times more sensitive to LTD4 than to methacholine. Significant correlations were found between the concentrati...

The effects of chronic bronchitis and chronic air-flow obstruction on lung cell populations recovered by bronchoalveolar lavage

Abstract: Bronchoalveolar lavage is used to evaluate parenchymal inflammation in patients with diffuse lung disease. Normal values for lavage cell counts and proteins are derived primarily from young subjects who are free from lung disease; however, older patients who undergo bronchoalveolar lavage often have used cigarettes for long periods of time and have developed variable degrees of chronic bronchitis and/or chronic air-flow obstruction. Therefore, we evaluated the effects of cigarette use, chronic bronchitis, and chronic air-flow obstruction on lavage cell populations by performing bronchoalveolar lavage in 48 male patients who were undergoing diagnostic fiberoptic bronchoscopy. Sixteen patients (33%) had elevated percentages of neutrophils (greater than or equal to 10%) in lavage fluid. Fourteen of these (87.5%) had chronic cough and/or phlegm production, but only 9 (64.3%) met criteria for definite chronic bronchitis. Patients with moderate or severe air-flow obstruction, defined spirometrically, had significantly greater percentages of lavage neutrophils and lower percentages of macrophages than did patients with mild or no air-flow obstruction. The first lavage aliquot contained the greatest proportion of neutrophils and the smallest proportion of macrophages. The percentage of neutrophils declined and the percentage of macrophages increased in sequential aliquots. The data indicate that patients with chronic cough and/or phlegm production and chronic air-flow obstruction may have increased proportions of neutrophils in bronchoalveolar lavage fluid in the absence of diffuse parenchymal lung disease or infections. These variables must be taken into account when interpreting lavage cellular analyses.(ABSTRACT TRUNCATED AT 250 WORDS)