Showing papers in "The American review of respiratory disease in 1989"
TL;DR: It is concluded that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.
Abstract: We have undertaken detailed cellular and ultrastructural examination of bronchial biopsies and bronchial lavage fluid from allergic asthmatic patients in order to determine the nature and degree of the inflammatory processes in mild allergic asthma. Eight atopic asthmatic patients (mean PC20 histamine, 0.90 mg/ml) and four nonasthmatic control subjects underwent fiberoptic bronchoscopy. All asthmatic subjects were clinically stable for 2 wk prior to bronchoscopy and required either no treatment or inhaled albuterol alone. A single 50-ml bronchial wash was undertaken, followed by endobronchial biopsy of subcarinae. These procedures were repeated in the asthmatic subjects 18 h after bronchial provocation with allergen or methacholine. Subsequently, all subjects underwent bronchial reactivity testing with inhaled histamine. The clinical and physiologic data were not revealed to the pathologist interpreting the specimens. The asthmatic subjects shed a significantly greater number of epithelial cells into the ...
1,142 citations
TL;DR: The light and electron microscopic structure of lobar bronchial biopsies taken at fiberoptic bronchoscopy from 11 atopic asthmatics, four of which were symptomatic and seven of whom were asymptomatic, was studied to study the structural changes in mild asthma.
Abstract: Little is known of the structural changes in mild asthma We have studied the light and electron microscopic structure of lobar bronchial biopsies taken at fiberoptic bronchoscopy from 11 atopic asthmatics, four of whom were symptomatic and seven of whom were asymptomatic The former and three of the latter had bronchial hyperresponsiveness to methacholine (PC20 < 4 mg/ml) Quantitative comparisons were made with biopsies from ten control subjects with normal airway reactivity; five had hay fever and five were nonatopic healthy volunteers Complete absence of surface epithelium was found in three cases of symptomatic asthma, and stratified squamous epithelium was present in the fourth A biopsy from one of the healthy control subjects had also lost its surface epithelium The degree of epithelial loss in all subjects correlated with the degree of airway reactivity (rs = 067, p < 0001) The reticular lamina of the epithelial basement membrane showed a trend toward thickening in the seven hyperreactive as
998 citations
TL;DR: It is concluded that the walls of the airways of patients with asthma are thickened by chronic inflammation and that this thickening could be as important as smooth muscle shortening in determining the airway responsiveness of these patients.
Abstract: This study was designed to determine the potential importance of airway wall thickening in the pathogenesis of the excess airways narrowing of asthma. The airways in postmortem specimens of lung obtained from 18 patients who suffered from asthma were compared to similar airways from 23 patients without asthma. Each airway was projected onto a digitizing board of a microcomputer to trace the internal and external perimeter of the airway and to calculate the submucosal and mucosal thicknesses. The relaxed length of the airway smooth muscle and the shortening required to occlude the airway lumen were calculated. These data show that the wall area was greater (p less than 0.001) in the membranous and cartilaginous airways of asthmatic patients and the airway smooth muscle shortening required to occlude the lumen was less in asthmatic than nonasthmatic airways (p less than 0.001). The increased wall area was due to increased areas of epithelium, muscle, and submucosa. We conclude that the walls of the airways of patients with asthma are thickened by chronic inflammation and that this thickening could be as important as smooth muscle shortening in determining the airway responsiveness of these patients.
828 citations
TL;DR: To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, 567 patients who had been receiving mechanical ventilation for more than 3 days in a unit were prospectively studied.
Abstract: Epidemiologic studies of nosocomial bacterial pneumonia in patients requiring mechanical ventilation have been limited because of the poor reliability of diagnosis procedures in this setting. To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, we prospectively studied 567 patients who had been receiving mechanical ventilation for more than 3 days in our unit. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. The diagnosis of V-A pneumonia was retained only if PSB specimens yielded > 103 cfu/ml of at least one microorganism, unless this result was established to be a false positive result on follow-up. V-A pneumonia developed in 49 patients for a total of 52 episodes (9%). The actuarial risk of V-A pneumonia was 6.5% at 10 days, 19% at 20 days, and 28% at 30 days of ventilation. Patients with pneumonia were sig...
811 citations
TL;DR: Examination of data from a second cross-sectional assessment of the association of air pollution with chronic respiratory health of children participating in the Six Cities Study of Air Pollution and Health suggests that children with hyperreactive airways may be particularly susceptible to other respiratory symptoms when exposed to these pollutants.
Abstract: Results are presented from a second cross-sectional assessment of the association of air pollution with chronic respiratory health of children participating in the Six Cities Study of Air Pollution and Health. Air pollution measurements collected at quality-controlled monitoring stations included total suspended particulates (TSP), particulate matter less than 15 microns (PM15) and 2.5 microns (PM2.5) aerodynamic diameter, fine fraction aerosol sulfate (FSO4), SO2, O3, and No2. Reported rates of chronic cough, bronchitis, and chest illness during the 1980-1981 school year were positively associated with all measures of particulate pollution (TSP, PM15, PM2.5, and FSO4) and positively but less strongly associated with concentrations of two of the gases (SO2 and NO2). Frequency of earache also tended to be associated with particulate concentrations, but no associations were found with asthma, persistent wheeze, hay fever, or nonrespiratory illness. No associations were found between pollutant concentrations and any of the pulmonary function measures considered (FVC, FEV1, FEV0.75, and MMEF). Children with a history of wheeze or asthma had a much higher prevalence of respiratory symptoms, and there was some evidence that the association between air pollutant concentrations and symptom rates was stronger among children with these markers for hyperreactive airways. These data provide further evidence that rates of respiratory illnesses and symptoms are elevated among children living in cities with high particulate pollution. They also suggest that children with hyperreactive airways may be particularly susceptible to other respiratory symptoms when exposed to these pollutants.(ABSTRACT TRUNCATED AT 250 WORDS)
681 citations
555 citations
TL;DR: Pressure support ventilation can assist spontaneous breathing and avoid diaphragmatic fatigue in patients demonstrating difficulties in weaning from the ventilator and clinical monitoring of sternocleidomastoid muscle activity allows the required level of pressure support to be determined to prevent fatigue.
Abstract: Persistent inability to tolerate discontinuation from mechanical ventilation is frequently encountered in patients recovering from acute respiratory failure. We studied the ability of inspiratory pressure support, a new mode of ventilatory assistance, to promote a nonfatiguing respiratory muscle activity in eight patients unsuccessful at weaning from mechanical ventilation. During spontaneous breathing, seven of the eight patients demonstrated electromyographic signs of incipient diaphragmatic fatigue. During ventilation with pressure support at increasing levels, the work of breathing gradually decreased (p less than 0.02) as well as the oxygen consumption of the respiratory muscles (p less than 0.01), and electrical signs suggestive of diaphragmatic fatigue were no longer present. In addition, intrinsic positive end-expiratory pressure was progressively reduced. For each patient an optimal level of pressure support was found (as much as 20 cm H2O), identified as the lowest level maintaining diaphragmatic activity without fatigue. Above this level, diaphragmatic activity was further reduced and untoward effects such as hyperinflation and apnea occurred. When electrical diaphragmatic fatigue occurred, the activity of the sternocleidomastoid muscle was markedly increased, whereas it was minimal when the optimal level was reached. We conclude that in patients demonstrating difficulties in weaning from the ventilator: (1) pressure support ventilation can assist spontaneous breathing and avoid diaphragmatic fatigue (pressure support allows adjustment of the work of each breath to provide an optimal muscle load); (2) clinical monitoring of sternocleidomastoid muscle activity allows the required level of pressure support to be determined to prevent fatigue.
517 citations
TL;DR: The hypothesis that factors related to nutritional status are an independent influence on the course of COPD is supported, as body weight was a powerful predictor of diffusing capacity in patients with the same FEV1.
Abstract: This study reviews the relationship between body weight, pulmonary function, and survival in the recent clinical trial of intermittent positive pressure breathing (IPPB). We related body weight, expressed as a percent of the ideal (%IBW), to the numerous other features of the disease recorded in this data set. Body weight was directly related to FEV1 (p = 0.0001), so that all subsequent analyses of body weight had to first consider FEV1. Mortality appeared to be influenced by body weight independent of FEV1. In patients with %FEV1 less than 35, mortality increased with decreasing body weight (p = 0.093), and this relationship was stronger in patients with %FEV1 35 to 47 (p = 0.048) and even stronger in patients with %FEV1 greater than 47 (p = 0.007). After adjusting for FEV1, body weight was a powerful positive correlate with exercise capacity (p = 0.0001). Body weight was also inversely related to %TLC (p = 0.0408) after adjusting for FEV1. Body weight was a powerful predictor of diffusing capacity (p = 0.0001) in patients with the same FEV1. These results support the hypothesis that factors related to nutritional status are an independent influence on the course of COPD.
498 citations
TL;DR: There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the Percentage of macrophages after exposure to O3, suggesting increased vascular permeability of the lung.
Abstract: Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 254 +/- 35), were exposed once to 04 ppm O3 and once to filtered air for 2 h with intermittent exercise Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation There was an 82-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3 Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 38-fold in the fluid while its activity increased 206-fold in the lavaged cells A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF) The level of complement fragment C3 alpha was increased by 17-fold The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells In addition, the amounts of fibrogenic-related molecules were assessed in BALF(ABSTRACT TRUNCATED AT 250 WORDS)
484 citations
TL;DR: Observations of a "GSH deficiency" in IPF ELF suggest that there is a marked oxidant-antioxidant imbalance at the alveolar surface of these persons, thus increasing the susceptibility to the severe epithelial cell damage characteristic of this disease.
Abstract: Glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH), a sulfhydryl-containing tripeptide produced by most mammalian cells, is an efficient scavenger of toxic oxidants, including hydrogen peroxide, an oxidant that plays a major role in the oxidant burden placed on the epithelial surface of the lower respiratory tract in chronic inflammatory states. GSH is present in the epithelial lining fluid of the normal lower respiratory tract, where it is thought to play a major role in providing antioxidant protection to the epithelial cells. In this regard, we hypothesized that the lower respiratory tract of patients with IPF may be chronically depleted of this antioxidant, thus leading to an increased susceptibility of lung epithelial cells to oxidant injury. To evaluate this concept, the concentration of glutathione was determined in the epithelial lining fluid of the lower respiratory tract of 15 patients with IPF and compared to that of 19 normal subjects. Strikingly, whereas ELF glutathione concentrations were high in normal subjects (429 +/- 34 microM), a fourfold decrease was found in patients with IPF (97 +/- 18 microM, p less than 0.001). In the context of the known oxidant burden present in the lower respiratory tract of patients with IPF, these observations of a "GSH deficiency" in IPF ELF suggest that there is a marked oxidant-antioxidant imbalance at the alveolar surface of these persons, thus increasing the susceptibility to the severe epithelial cell damage characteristic of this disease.
449 citations
TL;DR: Fibrosis in chronic idiopathic pulmonary fibrosis results mainly from organization of exudate within airspaces, just as it does after acute lung injury, and during this process, fibroblasts increase their synthesis of collagen and fibronectin coordinately.
Abstract: Fibroblasts in healthy adult lung are quiescent, synthesizing little collagen. We studied lung biopsies from 30 patients with pulmonary fibrosis, using immunohistochemistry with monoclonal antibodies against the propeptides of type I collagen to localize fibroblasts actively synthesizing collagen. Adjacent sections were stained with antibodies to type III and IV collagen, fibrin, cytokeratin, plasma fibronectin, or EDIIIa-containing "cellular" fibronectin (cFN). In rapid pulmonary fibrosis, including the proliferative phase of diffuse alveolar damage, organizing pneumonia, and subacute idiopathic fibrosis, collagen-synthesizing cells were numerous in organizing exudate filling airspaces but were also seen in the interstitium of the alveolar walls, interlobular septa, and walls of blood vessels. The new matrix deposited in the airspaces also contained type III collagen and EDIIIa-containing fibronectin. In chronic pulmonary fibrosis, more than half of the biopsies showed foci of collagen synthesis and cFN deposition near the air-tissue interface. The foci were consistently localized outside remnants of basal lamina and therefore within airspaces. The results indicate that (1) fibrosis in chronic idiopathic pulmonary fibrosis results mainly from organization of exudate within airspaces, just as it does after acute lung injury, and (2) during this process, fibroblasts increase their synthesis of collagen and fibronectin coordinately. Foci of active matrix deposition provide evidence for the progressive nature of chronic pulmonary fibrosis.
TL;DR: Results confirm prior observations showing the toxicity of MBP to tracheal epithelium and indicate that ECP and EPO alone, as well as EPO + GO + halide, cause damage, indicating that several eosinophil granule proteins are able to damage respiratory epithelia.
Abstract: We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 µg/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 µg/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2-producing enzyme glucose oxidase (GO), Cl−, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3....
TL;DR: It is concluded that DNTM is acquired by unpreventable environmental exposures that adversely affects survival of AIDS patients and effective therapeutic agents must be vigorously sought.
Abstract: We analyzed cases of disseminated nontuberculous mycobacterial infection (DNTM) in patients with AIDS reported to the Centers for Disease Control. Between 1981 and 1987, 2,269 cases were reported. In 96% of cases, infection was caused by M. avium complex (MAC). The number of cases has risen steadily since 1981, but the rate as a percentage of AIDS cases has remained stable at 5.5%. DNTM was seen less frequently in AIDS cases with Kaposi's sarcoma than in other AIDS cases (p less than 0.01). Rates of DNTM were lower in Hispanics and declined with age but were not significantly different by patient sex or means of acquiring HIV infection. Rates of disseminated MAC varied by geographic region from 3.9% to 7.8% (p less than 0.0001). As assessed by helper/suppressor T-cell ratios, AIDS patients with DNTM were not more immunologically impaired than those with other opportunistic infections. Life table analysis revealed that AIDS patients with DNTM survived a shorter time (median, 7.4 months) than did other AIDS patients (median, 13.3 months; p less than 0.0001). We conclude that DNTM is acquired by unpreventable environmental exposures. Because DNTM adversely affects survival of AIDS patients, effective therapeutic agents must be vigorously sought.
TL;DR: It is suggested that lung inflammation contributes substantially to respiratory impairment in patients with P. carinii pneumonia and increased lavage neutrophils (rather than parasite number) correlate with poorer oxygenation and poorer patient survival.
Abstract: Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS To determine differences in P carinii pneumonia in patients with and without AIDS, the P carinii parasite numbers, lung inflammatory cell populations, gas exchange, and survival were assessed in a series of 75 consecutive patients with P carinii pneumonia Bronchoalveolar lavage was used to quantify the parasite and inflammatory cell numbers in these patients The data from this study indicate: (1) patients with P carinii pneumonia and AIDS have significantly greater numbers of P carinii per ml of lavage compared to other immunocompromised patients with P carinii pneumonia (p < 00001); (2) patients with P carinii pneumonia and AIDS also have significantly fewer neutrophils recovered in the lavage compared to other immunocompromised patients with P carinii pneumonia (p = 00001); (3) patients with AIDS and P carinii pneumonia have higher arterial oxygen
TL;DR: To refine the functional guidelines for operability for lung resection, 55 consecutive patients with suspected lung malignancy thought to be surgically resectable were studied and the predictions of postoperative function correlated well with the measured values at 3 months.
Abstract: To refine the functional guidelines for operability for lung resection, we prospectively studied 55 consecutive patients with suspected lung malignancy thought to be surgically resectable. Lung function and exercise capacity were measured preoperatively and at 3 and 12 months postoperatively. Preoperative pulmonary scintigraphy was used to calculate the contribution to overall function by the affected lung or lobe and to predict postoperative lung function. Pneumonectomy was performed in 18 patients, lobectomy in 29, and thoracotomy without resection in six. No surgery was attempted in two patients who were considered functionally inoperable. Cardiopulmonary complications developed in 16 patients within 30 days of surgery, including three deaths. The predictions of postoperative function correlated well with the measured values at 3 months. For FEV1, r = 0.51 in pneumonectomy (p less than 0.05) and 0.89 in lobectomy (p less than 0.001). Predicted postoperative FEV1 (FEV1-ppo), diffusing capacity (DLCO), predicted postoperative DLCO (DLCO-ppo) and exercise-induced arterial O2 desaturation (delta SaO2) were predictive of postoperative complications including death and respiratory failure. In patients who underwent pneumonectomy, the best predictor of death was FEV1-ppo. The predictions were enhanced by expressing the value as a percentage of the predicted normal value (% pred) rather than in absolute units. For the entire surgical group a FEV1-ppo greater than or equal to 40% pred was associated with no postoperative mortality (n = 47), whereas a value less than 40% pred was associated with a 50% mortality (n = 6), suggesting that resection is feasible when FEV1-ppo is greater than or equal to 40% pred.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Visual inspection of the airways, as quantified by the bronchitis index, demonstrated significantly more evidence for inflammation in the chronic bronchitics than in either the asymptomatic smokers or the normal subjects.
Abstract: In order to characterize intraluminal airway inflammation in subjects with chronic bronchitis, bronchoscopy and bronchoalveolar lavage were performed in 28 subjects with chronic bronchitis with fixed airway obstruction and, for comparison, 15 asymptomatic smokers and 25 normal nonsmoking volunteers. The chronic bronchitics had a cough productive of sputum on most days of the month for 6 months in the preceding 2 yr, had at least one exacerbation requiring medical intervention in each of the previous 2 yr, and had an FEV1 less than 76% of predicted without response to bronchodilator. During bronchoscopy the airways were assessed for visual evidence of inflammation by assigning them a score, the bronchitis index, that graded the airways according to the apparent severity of airway edema, erythema, friability, and secretions. Bronchoalveolar lavage was performed by sequentially instilling and retrieving with gentle suction five 20-ml aliquots of sterile normal saline into each of three separate lobes. The first aliquots, the "bronchial" sample, were pooled and processed separately from the final four aliquots, the "distal" sample. Cell counts, cell differentials, and albumin were determined for both the bronchial and distal samples. In order to correlate inflammation with clinical parameters, sputum was collected for 24 h prior to bronchoscopy; spirometry was performed just prior to bronchoscopy, and smoking histories were obtained. Visual inspection of the airways, as quantified by the bronchitis index, demonstrated significantly more evidence for inflammation in the chronic bronchitics than in either the asymptomatic smokers or the normal subjects. The bronchial sample lavage fluids from the chronic bronchitics tended to contain more cells (6.1 +/- 2.2 x 10(6) cells) than the bronchial sample fluids from the asymptomatic smokers (3.6 +/- 0.6 x 10(6) cells) or normal subjects (3.7 +/- 0.5 x 10(6) cells). Furthermore, the chronic bronchitics had a higher percentage of neutrophils in their bronchial lavage fluid (35.8 +/- 5.6%) than did either the asymptomatic smokers (20.7 +/- 2.6%, p = 0.0001) or the normal subjects (10.3 +/- 5.6%). The distal sample lavage fluid also recovered more neutrophils from both the chronic bronchitics (15.0 +/- 4.2%, p = 0.0012) and asymptomatic smokers (5.7 +/- 1.3%, p = 0.002) than from the normal subjects (2.8 +/- 0.4%). The chronic bronchitics were divided into two groups: those with low (less than 20%) and those with high (greater than 20%) bronchial sample neutrophils. Those with higher bronchial sample neutrophils had significantly more sputum production and lower FEV1, FEV1/FVC, and FEF25-75 than did the subjects with lower bronchial sample neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: It is concluded that dampness in the home is common in many areas of the United States and that home dampness is a strong predictor of symptoms of respiratory and other illness symptoms among 8- to 12-yr-old children.
Abstract: This study examined the relationship between measures of home dampness and respiratory illness and symptoms in a cohort of 4,625 eight- to 12-yr-old children living in six U.S. cities. Home dampness was characterized from questionnaire reports of mold or mildew inside the home, water damage to the home, and the occurrence of water on the basement floor. Symptoms of respiratory and other illness were collected by questionnaire. Pulmonary function was measured by spirometry. Signs of home dampness were reported in a large proportion of the homes. In five of the six cities, one or more of the dampness indicators were reported in more than 50% of the homes. The association between measures of home dampness and both respiratory symptoms and other non-chest illness was both strong and consistent. Odds ratios for molds varied from 1.27 to 2.12, and for dampness from 1.23 to 2.16 after adjustment for maternal smoking, age, gender, city of residence, and parental education. The relationship between home dampness and pulmonary function was weak, with an estimated mean reduction of 1.0% in FEF25-75 associated with dampness and 1.6% with molds. We conclude that dampness in the home is common in many areas of the United States and that home dampness is a strong predictor of symptoms of respiratory and other illness symptoms among 8- to 12-yr-old children.
TL;DR: It is shown that all intraembryonic mesodermal tissues, except the prechordal plate, contain angiogenic precursors and that the control over vascular assembly resides within the connective-tissue-forming mesenchyme of the embryo.
Abstract: Embryonic blood vessels develop in two ways: angiogenesis, which is growth by budding, branching, and elongation of existing vessels, and in situ formation of endothelial vesicles that coalesce with elongating vessels. It is assumed that the former is more prevalent, with the latter restricted to vessels that form near the endoderm:mesoderm interface. Neither the relative contributions of each of these processes in the formation of specific blood vessels nor the origins of precursors (angioblasts) of these intraembryonic endothelial populations are known. Antibodies that recognize quail endothelial cells can be used to follow the movements and differentiation of endothelial cell precursors after the transplantation of putative precursor populations from quail into chick embryos. Using this method, it has been shown that all intraembryonic mesodermal tissues, except the prechordal plate, contain angiogenic precursors. After transplantation some angioblasts move in all directions away from the site of implantation, invading surrounding mesenchyme and contributing to the formation of arteries, veins, and capillaries in a wide area. Although it is clear that these invasive angioblasts, which behave unlike any other embryonic mesenchymal cell type, are found throughout the embryo, it is not known whether they represent a unique endothelial cell type in mature blood vessels. Irrespective of their original location in the donor embryo, transplanted angioblasts will form vascular channels that are appropriate for the tissues surrounding their site of implantation. These results indicate that the control over vascular assembly resides within the connective-tissue-forming mesenchyme of the embryo.
TL;DR: The results suggest that SP15 and SP35 have an important function in the structural organization of lipid membranes to form lattices.
Abstract: To analyze the mechanism of formation of tubular myelin (TM), we reconstituted TM from synthetic lipids and two surfactant-associated proteins (SP15 and SP35). SP15 was extracted from lyophilized pig pulmonary surfactant with 5% Triton X-100 and purified by DEAE-cellulose, CM-cellulose, and affinity chromatography with a specific antibody. SP35 was extracted from the precipitate of the 5% Triton X-100 extraction with pH 10 borate buffer and purified by DEAE-cellulose column chromatography. Lipid-SP15 complex was formed by a detergent dialysis method using octylglucopyranoside, and to this complex were added various concentrations of SP35 at 37° C. Structures similar to TM were formed when lipid-SP15 complex containing dipalmitoylphosphatidylcholine:phosphatidylglycerol from egg lecithin (2:1) and SP15 (lipid/protein, 5:1) was incubated with SP35 at concentrations of 0.15 to 0.22 mg/ml in CaCl2-containing buffer. At higher concentrations of SP35, many six-sided lattices were formed; the addition of EDTA ab...
TL;DR: The hypothesis that eosinophils and their products play a role in tissue injury in LPR and that eOSinophil infiltration may be associated with macrophage activation is supported.
Abstract: We have measured the total and differential cell counts, histamine, leukotriene (LT) B4 and LTC4, immunoglobulins, complement (C3), eosinophil-derived basic proteins, and monocyte complement rosettes in bronchoalveolar lavage (BAL) 6 h after challenge with either antigen or diluent control in seven patients with antigen-induced single early reactions, and seven with dual (early and late phase) reactions. In both groups, the total cell counts in BAL were similar, irrespective of whether they were challenged with antigen or diluent. However, in the late-phase responders (LPR), there were significant increases in lymphocytes, neutrophils, and eosinophils (p < 0.05), and significant decreases in the percentage of lung mast cells (p < 0.05). The eosinophil major basic protein and eosinophil-derived neurotoxin increased in four of five subjects with dual responses and in the majority of single early responders (SER). BAL histamine concentrations increased in five of seven patients with dual responses. There wer...
TL;DR: It is left little doubt that occupational exposure to dust and/or to Dust and fumes may be causally implicated in the genesis of COPD, according to accepted criteria for establishing causality.
Abstract: The increase in morbidity and mortality attributable to chronic obstructive pulmonary disease (COPD) has focused attention on environmental and host factors causally associated with the clinical entities included under the rubric of this term with a view to early preventive intervention. Despite the biologic plausibility of inhaled agents being causally implicated, only the role of tobacco smoke has been accepted beyond doubt. However, evidence implicating occupational exposures has accumulated, in particular over the last 2 yr, from: (1) community-based studies (in which larger study populations provide greater power than the usually smaller workforce based studies); (2) longitudinal studies of lung function (which enhance the signal of interest, namely the effects of the occupational exposures, and diminish the noise due to between-individual differences); (3) pathology studies (in which the outcome of interest is the quantitative measurement of emphysema), and (4) cohort mortality studies of all or specific causes of death. This evidence, reviewed here according to accepted criteria for establishing causality, leaves little doubt that occupational exposure to dust and/or to dust and fumes may be causally implicated in the genesis of COPD. As with tobacco exposure, both bronchitis (mucus hypersecretion) and airflow limitation are recognized as causally related to exposure, but not necessarily to each other. As with tobacco exposure, though effects are in general dose related to exposure, there is evidence for individual susceptibility. As with tobacco exposure, a possible host factor is the reactivity of airways to inhaled materials.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The results further support the conclusions from epidemiologic and experimental studies that the bacterial endotoxin is responsible for the acute reactions seen after exposure to many organic dusts, including that derived from cotton.
Abstract: In previous experiments, a good relationship was demonstrated between the amount of airborne bacterial endotoxin and acute reactions after exposure to organic dusts. In the present study, 77 naive subjects were exposed to isolated endotoxin (IE) or endotoxin attached to bacterial cells (CE). Both preparations were obtained from Enterobacter agglomerans, which is a major bacterial species in many organic dusts. The major physiologic effect caused was a dose-related decrease in transfer factor, as measured by carbon monoxide diffusion. Half of the subjects reported fever and about one-third a subjective feeling of chest tightness. The exposure also caused a dose-related but small decrease in FEV1. A slightly increased bronchial reactivity was demonstrated at 4 h after endotoxin exposure. The minute volume after CO2 exposure was marginally affected. The results further support the conclusions from epidemiologic and experimental studies that the bacterial endotoxin is responsible for the acute reactions seen after exposure to many organic dusts, including that derived from cotton.
TL;DR: The presence of PA is demonstrated at the location where physiologic damage in CF is most severe--the small bronchioles--strengthening the association between PA and pulmonary deterioration in CF and localize Pseudomonas aeruginosa in situ.
Abstract: Despite studies of the pathologic and microbiologic aspects of the lung in cystic fibrosis (CF), there is a lack of information on the lung localization of bacterial pathogens. Bacteriologic data come from cultures of sputum or accessible lung effluent from bronchoscopy. Our objective was to localize Pseudomonas aeruginosa (PA) in situ in order to provide descriptive data on the relationship between the presence of PA and disease of the surrounding tissue. Using stored, uncut blocks of preserved lung, we deparaffinized, cut, mounted, and reacted them with high-titer rabbit sera made to a mucoid strain of PA. The tissues were then reacted with a second antibody, biotinylated goat antirabbit immunoglobulin, developed using a peroxidase technique and counterstained with hematoxylin. PA organisms stained with heavy brown deposits and this was species-specific. In five patients with CF chronically colonized with PA, the organisms could easily be localized in multiple sections. Microscopic study demonstrated that location was generally endobronchiolar and associated with bronchiolar obliterative changes, mainly in small (less than 1 mm) airways. Extraluminal PA organisms were rare even when there was chronic interstitial inflammation. This study demonstrated the presence of PA at the location where physiologic damage in CF is most severe--the small bronchioles--strengthening the association between PA and pulmonary deterioration in CF.
TL;DR: It is demonstrated that BAL and TPC diagnose bacterial pneumonia in MV patients with similar accuracy and culture results from both techniques showed excellent qualitative and reasonable quantitative agreement.
Abstract: We compared the diagnostic value of quantitative cultures of bronchoalveolar lavage (BAL) and telescoping plugged catheter (TPC) samples in 34 nonimmunocompromised, mechanically ventilated (MV) patients with suspected bacterial pneumonia. A control group of seven “noninfected” MV patients was also studied. In 92% of patients with bacterial pneumonia (32 of 34), simple endotracheal aspiration samples recovered one or more microorganisms. Both BAL and TPC samples cultured colony-forming units (cfu) ⩾ 103/ml of one or more microorganisms in 56% (19 of 34) of patients. TPC and BAL culture results agreed on 88.5% (54 of 61) of the recovered microorganisms. Sterile TPC and BAL cultures agreed on 80% (4 of 5) of the cases. Microorganisms cultured from blood samples were also cultured from BAL and TPC specimens. Culture results from the two techniques completely disagreed in only one case (3%). In the control group, one TPC and two BAL cultures yielded microorganisms in cfu ⩾ 103/ml. Specificities of BAL and TPC ...
TL;DR: The term breathlessness may encompass multiple sensations, and, therefore, may not be explainable by a single physiologic mechanism.
Abstract: Various theories about the genesis of dyspnea have often assumed that the sensation is similar from patient to patient and is generated by a single underlying mechanism. To investigate whether breathlessness induced in normal volunteers by different stimuli represents one or more than one sensation, we studied 30 subjects in whom breathlessness was induced by each of 8 different stimuli: breath-holding, CO2 inhalation, inhalation of CO2, with ventilation voluntarily targeted below the level dictated by chemical drive, breathing with a resistive load, breathing with an elastic load, voluntary elevation of functional residual capacity, voluntary limitation of tidal volume, and exercise. For each stimulus, subjects were asked to choose description of their sensation(s) of breathlessness from a questionnaire listing 19 descriptors. The responses from this questionnaire were evaluated using cluster analysis to search for relationships among descriptors and to identify natural groupings. We found that distinct groups of descriptors emerged, i.e., subjects could distinguish different sensations of breathlessness. In addition, we found an association between certain descriptor groups and stimuli. We conclude that the term breathlessness may encompass multiple sensations, and, therefore, may not be explainable by a single physiologic mechanism.
TL;DR: The results suggest that the cough reflex will be increased in the presence of PGE2 in the airway, which may cause hyperresponsiveness to bronchoconstrictor agents in the lung and hyperalgesia in the skin.
Abstract: Prostaglandins may cause hyperresponsiveness to bronchoconstrictor agents in the lung and hyperalgesia in the skin. Increased airway concentration of both prostaglandins and bradykinin has been suggested as the possible cause of the increased cough sensitivity sometimes found in patients with cough associated with taking drugs that inhibit angiotensin-converting enzyme. We have therefore investigated the effect of prostaglandin E2 (PGE2), bradykinin (BK), histamine (H), and citric acid (C) on capsaicin-induced cough and increase in respiratory resistance (Rrs). Capsaicin-induced changes in Rrs and dose-cough response were measured before and after inhaling 0.76 mumol of PGE2, BK, H, and C. All the test substances caused cough, which was subject to tachyphylaxis, but no significant change in Rrs. Neither BK, H, nor C altered the capsaicin cough or Rrs response. However, PGE2 significantly increased both responses to capsaicin, the geometric mean (95% Cl) for the dose of capsaicin causing 5 or more coughs being 16.2 (14.3 to 18.3) nmol before and 4.4 (2.4 to 7.9) nmol after PGE2 (p less than 0.05). The percent increase (95% Cl) in Rrs after capsaicin was 20 (16.5 to 23.5)% before and 37.2 (32.2 to 43.2)% after PGE2 (p less than 0.05). The results suggest that the cough reflex will be increased in the presence of PGE2 in the airway.
TL;DR: It is concluded that nonspecific bronchial reactivity is only one mechanism underlying airflow obstruction in asthma, and that its relationship to the clinical state of asthma is not sufficiently close to be of practical clinical use.
Abstract: The contribution of nonspecific bronchial reactivity to the day-to-day clinical expression of asthma is uncertain. We have examined this relationship in a longitudinal study of eight children and 12 adults. Measurements of reactivity to methacholine were made every 2 to 3 wk over a period of 12 to 18 months, deriving the dose that caused a 20% fall in FEV1 (PD20). Throughout the study, all patients kept a daily record of symptoms and treatment and twice daily measurements of peak expiratory flow (PEF). A significant relationship was found between subjects' overall reactivity (median PD20) and both their average day-to-day variation in morning PEF (Spearman's rho = -0.53, p = 0.016) and diurnal variation in PEF (Spearman's rho = -0.60, p = 0.004). However, examining the temporal relationship between reactivity and asthma within subjects, individual PD20 measurements were not consistently related to concurrent asthma severity: in only six subjects did changes in PD20 generally reflect simultaneous trends in symptoms or PEF. In several patients, exacerbations of asthma occurred in the absence of bronchial hyperreactivity (PD20 greater than 12.8 mumol). We conclude that nonspecific bronchial reactivity is only one mechanism underlying airflow obstruction in asthma, and that its relationship to the clinical state of asthma is not sufficiently close to be of practical clinical use.
TL;DR: It is concluded that ET tubes contribute significantly to total airflow resistance and that RET is often significantly greater than indicated by in vitro studies.
Abstract: The mechanics of gas flow in endotracheal (ET) tubes have been evaluated extensively in vitro under static and dynamic conditions. Previous bedside determinations of respiratory system mechanics in patients with acute respiratory failure have been based on assumptions derived from in vitro measurements without direct measurement of in vivo ET tube resistance (Ret). We hypothesized that the Ret measured in vivo would be greater than those values obtained in vitro when peak flow rates and ET tube size were held constant. We measured airflow, volume (pneumotachograph), esophageal pressure (nasogastric-esophageal balloon), and airway pressure (airway catheter) in 10 patients intubated with no. 8.0 orotracheal tubes. We also studied the static and dynamic flow-pressure relationships for five different sizes of ET tubes in vitro (artificial lung) (6.0, 7.0, 7.5, 8.0, and 8.5). The static and dynamic values of Ret and the Rohrer coefficients of linear and nonlinear resistance (K1 and K2) were similar to values p...