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Showing papers in "The American review of respiratory disease in 1988"


Journal ArticleDOI
TL;DR: An expanded definition of ARDS is proposed that takes into account new knowledge about adult respiratory distress syndrome and its clinical features, physiologic disturbances, prognosis, and pathologic findings.
Abstract: More than twenty years ago, Ashbaugh and coworkers, (1), in a now classic article, described. 12 patients whose striking but uniform clinical, physiologic, roentgenographic,and pathologic abnormalities distinguished them from among 272adult patients who had received respiratory support in the intensive care units of Colorado General Hospital and Denver General Hospital. The 12patients all had severedyspnea, tachypnea, cyanosis that was refractory to oxygen therapy, decreased respiratory system compliance, and diffuse alveolar infiltrations on their chest radiographs. Pathologic examination in seven patients who died revealed atelectasis, vascular congestion and hemorrhage, severe pulmonary edema and hyaline membranes. Shortly afterward, Petty and coworkers (2), called this constellation of findings the adult respiratory distress syndrome (ARDS). Since then, ARDS has been recognized as an entity throughout the world and has been the subject of numerous conferences, hundreds of articles, and several books. As a result of this activity, much descriptive information has been obtained about ARDS, and we have learned a lot about its clinical features, physiologic disturbances, prognosis, and pathologic findings. And yet formidable problems remain: there is disagreement about exactly what ARDS is and on what causes it; more importantly, available empiric treatment is inadequate, and mortality remains unacceptably high (600/0 or more) (3). This appears to be one of the few points of agreement among investigators, but even that statement is arguable (4). We believe that much of the controversy concerning ARDS is explained by the lack of a satisfactory definition of this elusivesyndrome. How can you collect, much less compare, epidemiologicdata and mortality figures when there is no uniformly accepted (and used) definition? How can you study basic pathophysiologic mechanisms, understand natural history, and above all, evaluate new therapeutic approaches in what appears now to be an amalgam of many different disorders? The purpose of this article, therefore, is to propose an expanded definition of ARDS that takes into account new knowledge about

2,372 citations


Journal ArticleDOI
TL;DR: To the authors' knowledge, this constitutes the first example of a protective effect of PEEP during permeability edema, which was markedly reduced by PEEP and preserved the normal ultrastructural aspect of the alveolar epithelium.
Abstract: The respective roles of high pressure and high tidal volume to promote high airway pressure pulmonary edema are unclear. Positive end-expiratory pressure (PEEP) was shown to reduce lung water content in this type of edema, but its possible effects on cellular lesions were not documented. We compared the consequences of normal tidal volume ventilation in mechanically ventilated rats at a high airway pressure (HiP-LoV) with those of high tidal volume ventilation at a high (HiP-HiV) or low (LoP-HiV) airway pressure and the effects of PEEP (10 cm H2O) on both edema and lung ultrastructure. Pulmonary edema was assessed by extravascular lung water content and microvascular permeability by the dry lung weight and the distribution space of 125I-labeled albumin. HiP-LoV rat lungs were not different from those of controls (7 cm H2O peak pressure ventilation). By contrast, the lungs from the groups submitted to high volume ventilation had significant permeability type edema. This edema was more pronounced in LoP-HiV...

1,520 citations


Journal ArticleDOI
TL;DR: This study supports the hypothesis that bronchial hyperresponsiveness is secondary to epithelial cell damage mediated through eosinophil-derived granule products.
Abstract: We have performed bronchoalveolar lavage (BAL) on 17 subjects with mild atopic asthma (9 symptomatic, 8 asymptomatic) and 14 nonasthmatic control subjects (6 hay fever, 8 nonatopic). There was a significant increase in the percentage of mast cells in both groups of asthmatics although the counts were no different from those previously reported for a number of other respiratory diseases. Asthmatics with airway hyperreactivity (PC20 less than 4 mg/ml) had significant increases in spontaneous histamine release. There was a significant elevation in the eosinophil count and the concentration of major basic protein (MBP) in BAL fluid in the symptomatic asthmatics. Furthermore, there was a significant correlation between the amounts of MBP recovered and the percentage of eosinophils in the BAL. These changes were even more marked when asthmatics with airway hyperreactivity were compared with subjects with normoreactive airways. In addition, there was a significant increase in the percentage of epithelial cells in the hyperreactive asthmatics. There was an inverse correlation between the PC20 and the percentage of mast cells (p less than 0.01), eosinophils (p less than 0.05), and epithelial cells (p less than 0.05) and amount of MBP in BAL (p less than 0.01). This study supports the hypothesis that bronchial hyperresponsiveness is secondary to epithelial cell damage mediated through eosinophil-derived granule products.

912 citations


Journal ArticleDOI
TL;DR: It is concluded that patients with obstructive sleep apnea have a significantly higher frequency of auto accidents than do subjects without apnea.
Abstract: Although patients with obstructive sleep apnea often report falling asleep while driving, the frequency of auto accidents involving these patients has not been rigorously studied. Therefore, we compared the driving records of 29 patients with obstructive sleep apnea with those of 35 subjects without sleep apnea. The patients with sleep apnea had a sevenfold greater rate of automobile accidents than did the subjects without apnea (p < 0.01). The percentage of persons with one or more accidents was also greater in the patients with apnea than in the control subjects without apnea (31% versus 6%, p < 0.01). The percentage of persons having one or more accidents in which they were at fault was also greater in the patients with apnea than in the control subjects (24% versus 3%, p < 0.02). The automobile accident rate of the patients with sleep apnea was 2.6 times the accident rate of all licensed drivers in the state of Virginia (p < 0.02). In addition, 24% of patients with sleep apnea reported falling asleep ...

596 citations


Journal ArticleDOI
TL;DR: In this review, scientific developments on the study of cilia and mucus, and interactions between them, are drawn together to further understanding of mucociliary clearance mechanisms of the respiratory tract.
Abstract: The presence of cilia on epithelia of the respiratory tract was reported more than 150 yr ago, and the two-layer model of mucus transport was put forward more than 50 yr ago. However, it is only in the last 10 yr or so that the motion of mucus-propelling cilia of the mammalian respiratory system has been adequately described, and fluid dynamic studies have developed far enough to allow descriptions of the mechanisms by which ciliary movement is coupled to mucus transport. In this review, scientific developments on the study of cilia and mucus, and interactions between them, are drawn together to further understanding of mucociliary clearance mechanisms of the respiratory tract. The study of the cilia incorporates a discussion of the internal mechanics and biochemistry of the ciliary axoneme, the physical principles of the beat pattern, and the (weak) metachronal coordination of cilia in the lung. Mucus rheology plays a central role in mucociliary transport with the rheologic properties of the mucus determining the effective functioning of this clearance mechanism. Theoretical models provide information on the mechanical principles of the beat pattern as well as providing reliable estimates of the transport rates. Although airflow is not thought to contribute to mucus transport in the normal state, high frequency ventilation and coughing may make significant contributions.

554 citations



Journal ArticleDOI
TL;DR: A prospective, randomized, double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury, including the adult respiratory distress syndrome (ARDS), or improve mortality when administered early in septic shock.
Abstract: We conducted a prospective, randomized, double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury, including the adult respiratory distress syndrome (ARDS), or improve mortality when administered early in septic shock. All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1, 1983 and August 29, 1986 were eligible for admission to the study if they had either (1) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values (in already hospitalized patients), or (2) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg (in newly admitted patients). Patients meeting these criteria were excluded if they (1) had severe immunodeficiency, (2) were less than 18 or greater than 76 yr of age, (3) had multilobar roentgenographic infiltrates, or (4) were already receiving corticosteroids. Eighty-seven patients enrolled in the study received either methylprednisolone, 30 mg/kg per dose, or mannitol placebo for a total of 4 doses every 6 h, following the presumptive diagnosis of septic shock. Of these patients, 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry. Thirteen of the patients who received methylprednisolone developed ARDS, compared to 14 patients who received placebo. Lesser degrees of parenchymal lung injury did not differ between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

482 citations


Journal ArticleDOI
TL;DR: It is confirmed that hypopneas are clinically important and that the "sleep apnea syndrome" may occur in the absence of recurrent apneas.
Abstract: We have observed patients who clinically have the obstructive sleep apnea syndrome but have no apneas, instead having recurrent nocturnal hypoventilation. There is disagreement about the definition and significance of such sleep-related hypopneas. We have thus analyzed breathing patterns, oxygenation and sleep records of 50 consecutive patients referred with the clinical features of the sleep apnea syndrome and found to have abnormal breathing during sleep to determine: (1) the best definition of hypopnea, and (2) how frequently patients have the clinical features of the sleep apnea syndrome without recurrent apneas. Hypopnea definitions based on decreases in thoracoabdominal movement yielded hypopnea frequencies that were significantly closer to desaturation and arousal frequencies than hypopnea definitions based on flow reduction. The best hypopnea definition was that of a 50% reduction in thoracoabdominal movement lasting for 10 s. This was validated in 33 normal subjects, all of whom had fewer than 11 hypopneas/h, and fewer than 14 apneas plus hypopneas/h of sleep. Thirty-two of the 50 patients had 10 or more apneas/h, the remaining 18 having 9 to 98 hypopneas/h such that all patients had more than 16 apneas plus hypopneas/h. Patients with recurrent hypopneas were clinically indistinguishable from and had a similar frequency of 4% desaturations (zero to 104/h) and arousals (7 to 98/h) to the patients with frequent apneas. This study confirms that hypopneas are clinically important and that the "sleep apnea syndrome" may occur in the absence of recurrent apneas.

470 citations


Journal ArticleDOI
TL;DR: It is suggested that the appearance of pulmonary infiltrates and purulent tracheal secretions does not result from bacterial pneumonia in a majority of patients.
Abstract: To determine the usefulness of samples obtained by bronchoscopy using a protected specimen brush and evaluated by quantitative culture techniques in establishing the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation, we prospectively studied 147 ventilated patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. Positive cultures of protected brush specimens (greater than 10(3) cfu/ml) were found in only 45 patients (31%). Subsequent follow-up confirmed the diagnosis of pneumonia in 34 of 45 patients, and in only 4 of 45 patients was a positive culture firmly established to be a false positive result. No patient with less than 10(3) cfu/ml was subsequently shown to have had pneumonia, and the diagnosis was definitely excluded in 72 of 102 patients by the absence of pneumonia at autopsy or recovery without antibiotic therapy. In contrast, when 16 clinical variables were evaluated by stepwise logistic regression analysis, no combination could be identified that was useful in distinguishing patients with bacterial pneumonia. Furthermore, when the actual costs of evaluation and therapy of our patients were compared with the projected costs entailed in treating all patients suspected of having pneumonia with antibiotics, evaluation using the protected specimen brush and quantitative cultures was less expensive after only 6 days of treatment. These results suggest that the appearance of pulmonary infiltrates and purulent tracheal secretions does not result from bacterial pneumonia in a majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

422 citations


Journal ArticleDOI
TL;DR: High performance liquid chromatography indicated that NKA-LI consisted of several cross-reacting substances, presumably other peptides of the tachykinin family, which was the most potent one to contract tracheal smooth muscle of guinea pigs in vitro.
Abstract: Recent evidence suggests that activation of airway C-fibers, besides causing afferent transmission, also causes release of transmitters from peripheral endings, probably via local axon reflexes, resulting in effects on vascular and bronchial smooth muscle, i.e., vasodilatation, increase in vascular permeability, and bronchoconstriction. In the present study, the release of tachykinins was investigated in the perfused guinea pig lung by various ways of neuronal activation. Substance-P-like immunoreactivity (SP-LI) and neurokinin-A-like immunoreactivity (NKA-LI) was determined by radioimmunoassay in the perfusates. A significantly increased outflow of both SP-LI and NKA-LI was observed during perfusion of the lung with high potassium concentration (60 mM), the C-fiber activator capsaicin (1 µM), bradykinin (1 µM), histamine (100 µM), or the nicotinic agonist dimethylphenyl piperazinium (DMPP) (32 µM). Release of both SP-LI and NKA-LI could also be achieved by electrical stimulation of vagal nerves. The perc...

406 citations


Journal ArticleDOI
TL;DR: It is concluded that maintenance of alveolar volume is a key mechanism in the prevention of lung injury during mechanical ventilation of the atelectasis-prone lung.
Abstract: Controversy exists whether high frequency oscillatory ventilation with an active expiratory phase (HFO-A) should be used at low ventilator pressures or high alveolar volumes to minimize lung injury in the atelectasis-prone lung. We therefore ventilated 20 anesthetized, tracheostomized rabbits made surfactant-deficient by lung lavage in 1 of 3 ways: HFO-A at a high lung volume (HFO-A/HI), HFO-A at a low lung volume (HFO-A/LO), or conventional mechanical ventilation (CMV); all received 100% oxygen for 7 h. We examined oxygenation, lung mechanics, and lung pathology.Arterial oxygenation in the HFO-A/HI rabbits was kept > 350 mm Hg. Mean lung volume above FRC in these animals was 23.4 ml/kg. In rabbits ventilated with HFO-A/LO and CMV, arterial oxygen tensions were 70 to 100 mm Hg. Mean lung volumes were 7.8 and 4.3 ml/kg, respectively.Total respiratory system pressure-volume curves (P-V curves) showed no change from baseline in the HFO-A/HI group after 7 h of ventilation. The low lung volume groups (HFO-A/LO...


Journal ArticleDOI
TL;DR: In this paper, concentrations of tryptase and histamine in bronchoalveolar lavage fluid (BALF) were used as indicators of pulmonary mast cell activation.
Abstract: Human mast cells likely play a significant role in human asthma. In the present study, concentrations of tryptase and histamine in bronchoalveolar lavage fluid (BALF) were used as indicators of pulmonary mast cell activation. BALF was obtained before and after endobronchial allergen challenge and assessed for mediator content and cell composition in 4 subject groups: nonatopic nonasthmatics (Group 1, n = 7), nonatopic asthmatics (Group 2, n = 3), atopic nonasthmatics (Group 3, n = 7), and atopic asthmatics (Group 4, n = 7). Before challenge, histamine concentrations were not different between the 4 groups, whereas tryptase concentrations were significantly greater in the atopic asthmatics than in each of the other groups (p < 0.04). Allergen challenge in atopic asthmatics resulted in significant increases above baseline in mean ± SD histamine (0.7 ± 7.1 to 2.8 ± 2.0 ng/ml) and tryptase (2.0 ± 1.7 to 10.1 ± 8.2 ng/ml) concentrations in BALF (p < 0.03). Atopic nonasthmatics also had increases above baseline...

Journal ArticleDOI
TL;DR: The quantitative CT scan can diagnose, quantitate, and locate mild to moderate emphysema, in humans, in life, noninvasively.
Abstract: We used a computerized microscopic image analysis system to directly measure the surface area of distal air spaces in methacrylate-embedded blocks randomly selected from inflation-fixed lobes that were resected from 45 patients as treatment of their peripheral lung tumors. In 28 of these patients, a preoperative computer tomography (CT) scan, at 6 and 10 cm below the sternal notch, was used to generate frequency histograms of CT numbers (measured as EMI units), a measure of lung density, in pixels from the lung or lobe that was subsequently resected. A similar CT number histogram was also derived from the lateral two fifths of the area of lobe/lung that was to be resected. The EMI unit that defined the lowest fifth percentile of this latter histogram correlated (n = 28, r = -0.77, p less than 0.001) with the mean value of the surface area of the walls of distal airspaces per unit lung volume (AWUV) in the five 1 mm x 1 mm microscopic fields with the lowest AWUV values, out of the 20 to 35 such fields examined in each patient. In the 34 of the 45 patients in whom we also measured volume-corrected diffusing capacity (DLCO/VA), this also correlated (n = 34, r = 0.84, p less than 0.001) with this value of AWUV, which measures the surface area of airspaces distal to the terminal bronchioles--reflecting an increase in airspace size, a defining characteristic of emphysema. However, a low DLCO/VA is nonspecific, whereas an abnormally low regional lung density is more likely to be specific for emphysema. In addition, highlighting those pixels of the CT display with low CT numbers (i.e., EMI units -500 [air] to -450, where zero = water) can locate areas of macroscopic emphysema, as shown by subsequent pathologic examination. Thus the quantitative CT scan can diagnose, quantitate, and locate mild to moderate emphysema, in humans, in life, noninvasively.


Journal ArticleDOI
TL;DR: Early diagnosis, aggressive treatment, and prophylaxis of complications should increase survival in patients with acute respiratory failure.
Abstract: Acute respiratory failure is frequently fatal. Attempts to decrease mortality must include attention to pulmonary and extrapulmonary complications. Pulmonary complications include pulmonary emboli, barotrauma, fibrosis, and pneumonia. Swan-Ganz catheters, tracheal intubation, and mechanical ventilation can also result in pulmonary complications. Extra-pulmonary complications such as gastrointestinal hemorrhage, renal failure, infection, and thrombocytopenia may increase mortality. Early diagnosis, aggressive treatment, and prophylaxis of complications should increase survival.

Journal ArticleDOI
TL;DR: To study whether TNF could induce acute lung injury similar to that seen in gram-negative sepsis, recombinant human TNF (rHuTNF alpha) was injected into guinea pigs and monitored arterial blood gases, leukocyte counts, and left atrial (Pla), pulmonary artery (Ppa), and mean arterial pressures serially for 8 h.
Abstract: Tumor necrosis factor α (TNF), a monokine produced by mononuclear cells in response to bacterial endotoxin (LPS), creates a syndrome similar to septic shock in animal models. To study whether TNF could induce acute lung injury similar to that seen in gram-negative sepsis, we injected recombinant human TNF (rHuTNFα) into guinea pigs and monitored arterial blood gases, leukocyte counts, and left atrial (Pla), pulmonary artery (Ppa), and mean arterial pressures (MAP) serially for 8 h. Pulmonary histopathology was assessed microscopically, and cell counts and 125I-labeled albumin (125I-albumin) in bronchoalveolar lavage (BAL) fluid and lung wet/dry weight ratios were determined. Five groups of animals were studied; the 2 TNF groups received high (1.4 × 106 U/kg) or low (1.0 × 106 U/kg) doses of rHuTNFα, the sepsis group received 2 × 109 Escherichia coli/kg intravenously, and the control group received saline. An LPS control group receiving 40 ng/kg E. coli LPS was also included because the rHuTNFα contained a...

Journal ArticleDOI
TL;DR: Data presented here indicate that freshly fractured silica exhibits surface characteristics and biologic reactivity distinct from aged silica, and on this basis it is proposed that these surface features may lead to enhanced manifestations of lung injury.
Abstract: Data presented here indicate that freshly fractured silica exhibits surface characteristics and biologic reactivity distinct from aged silica, and on this basis we propose that these surface features may lead to enhanced manifestations of lung injury. Grinding of silica produces ∼1018 Ṡi and Si-Ȯ (silicon-based) radicals per gram of dust on the particulate surface which are characterized by an electron spin resonance (ESR) spectrum centered around g = 2.0015. These silicon-based radicals react with aqueous media to produce ȮH radicals, which are demonstrable using a DMPO spin trap. The concentration of silicon-based radicals in silica decreases with aging in air and exhibits a half-life of ∼30 h, whereas its ability to generate ȮH radicals in aqueous solution decreases with a half-life of ∼20 h. However, on storage in aqueous media, the concentration of silicon-based radicals and the dust's ability to generate ȮH radicals decrease significantly within a few minutes. Freshly ground silica is also more biol...

Journal ArticleDOI
TL;DR: The cumulative probability of survival of the patients with alpha 1AT deficiency and symptomatic emphysema indicated a significantly shortened lifespan with a mean survival of 16% at 60 yr of age compared with 85% for normal persons.
Abstract: Alpha-1-antitrypsin (alpha 1AT) deficiency is a hereditary disorder characterized in adults by a high risk for the development of severe destructive lung disease at an early age. The present study was designed to draw conclusions concerning the characteristics of a referral population of 124 patients with alpha 1AT deficiency and symptomatic emphysema. Typically, the alpha 1AT level was 30 mg/dl, and the alpha 1AT phenotype was almost always PiZZ. The individuals in this population were most often male, caucasian, and ex-smokers, and they had become dyspneic between 25 and 40 yr of age. Most routine blood tests were normal. The chest radiographs and ventilation-perfusion studies typically showed abnormalities with a lower zone distribution, and about one third of the study population had evidence suggestive of pulmonary hypertension. Lung function tests were typical for emphysema; the FEV1 and DLCO were the parameters most dramatically reduced, and the annual rate of decline of those parameters was greater than that of the general population. The cumulative probability of survival of this population indicated a significantly shortened lifespan with a mean survival of 16% at 60 yr of age compared with 85% for normal persons.

Journal ArticleDOI
TL;DR: BAL provides the best reflection of the lung's bacterial burden, both quantitatively and qualitatively, in the setting of prolonged intubation and ventilation.
Abstract: Cultures of tracheal secretions, bronchoalveolar lavage (BAL), protected specimen brushes (PSB), and direct lung aspirates were compared with cultures of lung homogenates and histologic findings in 35 baboons after 7 to 10 days of intubation and mechanical ventilation. Six animals received no antibiotics, while the remainder were treated with a variety of prophylactic regimens of intravenous and topical agents. Bacterial contamination at each culture site was expressed as a “bacterial index” (BI), obtained as the sum of the logarithmic concentrations of individual species. In the absence of antibiotics, pneumonias occurred in all animals and were polymicrobial; 56% of organisms in lung tissue were members of the normal upper respiratory tract flora, while 44% were gram-negative bacilli with a mean total bacterial index of 13.94/g. Lobar tissue BI values > 6.0/g were found in 77% of lobes containing pneumonias judged by histologic criteria to be moderate or severe in extent, whereas only 7% of lobes with l...

Journal ArticleDOI
TL;DR: After 3 months of supplementary oral nutrition, there was a significant improvement in the nutritional status of Group 1 patients, as evidenced by an increase in body weight, triceps skinfold thickness, and midarm muscle circumference.
Abstract: We carried out a prospective, randomized, controlled trial to investigate the effect of a 3-month period of supplementary oral nutrition in 14 poorly nourished outpatients with COPD. Seven patients were randomized into Group 1 who received their normal diet during Months 1 to 3, a supplemented diet during Months 4 to 6, and their original normal diet during Months 7 to 9. The other 7 patients received their normal diet for the entire 9-month study period (Group 2). Seven well-nourished patients (Group 3) matched for age and severity of air-flow obstruction served as control subjects; they received their normal diet for the 9-month study period. Measurements of nutritional status, respiratory muscle and handgrip strength, sternomastoid muscle function (including frequency/force curves, maximal relaxation rate, and a fatigability test), lung function, arterial blood gas tensions, general well-being and breathlessness scores, and 6-min walking distances were carried out monthly in all patients. At the start of the study, the poorly nourished patients had lower mean daily calorie and protein intakes than did the well-nourished patients. The poorly nourished patients had lower respiratory muscle and handgrip strength, and abnormal contractility and increased fatigability of the sternomastoid muscle compared with those in the well-nourished patients. After 3 months of supplementary oral nutrition, there was a significant improvement in the nutritional status of Group 1 patients, as evidenced by an increase in body weight, triceps skinfold thickness, and midarm muscle circumference. Respiratory muscle and handgrip strength increased in parallel with nutritional status, although there were no significant changes in lung function or arterial blood gas tensions.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: The data suggest that a major effect of cigarette smoking on lung function decline involves the premature onset of a "normal" rate of decline in function and, to a lesser extent, more rapid rates of decline later in life.
Abstract: Epidemiologic investigations into the natural history of airway obstructive disease have focused on both the growth and decline of lung function measurements. Although a general picture has emerged as to overall patterns of growth/decline, uncertainty remains with regard to important details of these patterns. Pulmonary function data from subjects aged 5 yr and and older who participated in any or all of the first 10 annual surveys of the East Boston population-based study have been used to investigate patterns of growth and decline of lung function derived from maximal forced expiratory maneuvers. At each annual survey, subjects completed a standardized respiratory illness and smoking questionnaire and provided forced expiratory volume-time curves from which forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were derived. A nonparametric curve smoothing method was used to provide an overall summary of growth and decline of each measure of function. Asymptomatic, nonsmoking males demonstrated a pattern of growth of FEV1 that included a prolonged plateau phase or period of slow, continued growth from ages 23 to 35 yr. Decline in lung function began after this period and occurred in two phases that averaged about -20 and -30 ml/yr. In contrast, no plateau phase was observed for male current smokers. In these smokers, decline in FEV1 began in the early part of the third decade at a rate only slightly greater than that observed for nonsmokers (-25 to -30 ml/yr). Similar patterns and rates of decline were observed for females, although the presence of a plateau phase was less clearly discernible. These data suggest that a major effect of cigarette smoking on lung function decline involves the premature onset of a "normal" rate of decline in function and, to a lesser extent, more rapid rates of decline later in life and that the pattern and magnitude of decline is similar in males and females.

Journal ArticleDOI
TL;DR: An inflammatory cell influx associated with the nasal late-phase response to antigen challenge is demonstrated and an important pathogenetic role for the eosinophil is suggested.
Abstract: Previous studies have demonstrated symptoms and mediator release occurring as long as 11 h after nasal challenge with antigen in selected allergic subjects. Pretreatment with systemic steroids reduced symptoms and mediators including histamine, TAME-esterase activity, and kinins. The aims of the present study were to characterize the cell influx during the late-phase response to antigen challenge and to determine the effect of pretreatment with systemic steroids on this response. We examined cytospin slides of nasal washings obtained before and hourly for 11 h after nasal antigen challenge in 10 asymptomatic allergic subjects with a history of seasonal rhinitis and 5 normal, nonallergic subjects. Allergic subjects received oral prednisone (20 mg 3 times a day) or placebo in a random, double-blind crossover manner for 2 days before each of 2 challenges 1 month apart. On placebo days, a mixed cell influx occurred in allergic subjects during the late response that was 50-fold greater than the cell influx in ...

Journal ArticleDOI
TL;DR: It is concluded that the 30% load was more effective than the 15% load in this sample of patients and improved the following: Plmax, endurance time, and 12MD.
Abstract: The inspiratory pressure load is an important variable in inspiratory muscle training (IMT), but previous studies with chronic obstructive pulmonary disease (COPD) patients have not controlled for this variable. We compared the effects of two months of IMT with a pressure threshold breathing device at inspiratory pressure loads equal to either 15 or 30% of each patient's maximal inspiratory pressure (Plmax). This study was double blind and patients were randomly assigned to the treatment groups, 12 in the 15% group and ten in the 30% group. Dependent variables were measured at baseline, and after one and two months of IMT. Patients who exercised with the 30% load improved the following: Plmax by a mean of -12 +/- 9 cm H2O (p less than 0.01), endurance time while breathing against an inspiratory pressure load equal to 66% of Plmax by 5 +/- 9 min (p less than 0.01), and 12-min distance walk (12MD) by 199 +/- 90 feet (p less than 0.01). Patients who exercised with the 15% load demonstrated no improvements in Plmax, endurance time, and 12MD. There were no changes in patients' report of functional impairment (Sickness Impact Profile), mood (Profile of Mood States), health status (Health Perceptions Questionnaire), and pulmonary symptoms (respiratory symptom log). We conclude that the 30% load was more effective than the 15% load in this sample.

Journal ArticleDOI
TL;DR: It is hypothesized that passive smoking, by increasing the frequency of BR and of atopy, may increase the risk of asthma in childhood and particularly in boys.
Abstract: We studied the relationship between parental smoking habits and atopy and bronchial responsiveness (BR) in 9-year-old, non-selected schoolchildren. A questionnaire on respiratory disease and maternal and paternal smoking habits was administered to one parent. Skin prick tests using the most common allergens present in central Italy, a flow-volume spirometric test, and a bronchial provocation test using carbachol in increasing doses were performed. Male children with smoking parents had significantly increased BR when compared to those whose parents did not smoke (Odds Ratio (OR) = 4.3, p = 0.009). No such significant increase in BR was found in female children of smoking parents (OR = 1.5, p = 0.4). The relationship between BR in children and smoking in parents was stronger in asthmatics (p = 0.02), but was still significant after controlling for asthma and atopy. Bronchial responsiveness was significantly correlated with atopy (p = 0.001). This was also true for nonasthmatic children and for both males a...

Journal ArticleDOI
TL;DR: A guinea pig model of asthma in which animals were sensitized and challenged by inhalation of aerosolized ovalbumin represents a useful animal model in which to study the mechanism of early and late bronchoconstriction responses.
Abstract: We describe a guinea pig model of asthma in which animals were sensitized and challenged by inhalation of aerosolized ovalbumin. Challenge was performed under cover of mepyramine (10 mg/kg) to allow a high enough concentration of ovalbumin to elicit consistent late responses. Airway resistance and thoracic gas volume of conscious guinea pigs was assessed by whole body plethysmography before and at regular intervals for as long as 72 h after challenge. At the same time points, cellular changes in the lung were assessed by both examination of cells recovered by bronchoalveolar lavage (BAL) and lung histology. There were no significant changes in specific airway conductance (SGaw), BAL cell content or lung histology in animals challenged with saline control. Challenge with 2% ovalbumin caused an early fall in SGaw, which peaked at 2 h and amounted to a 43.7 +/- 4.1% fall from baseline. This was followed by 2 late responses, the first reaching maximum at 17 h with a 46.9 +/- 4.5% decrease in SGaw from baseline and the second at 72 h with a 39.0 +/- 3.5% fall in SGaw. Examination of BAL fluid revealed a 7-fold increase in neutrophils at 6 h and a 17-fold increase at 17 h, after which numbers decreased to baseline. Eosinophilia developed more slowly, being insignificant at 6 h and 6-fold at 17 h; by 72 h, eosinophils constituted 48.9 +/- 6.9% of the total cells recovered. No changes in mononuclear cells or lymphocytes were observed. Histologic examination of the lung revealed a progressive eosinophil infiltration of the airways, but not alveoli or vascular bed. Electron microscopy showed degranulation of eosinophils recovered by BAL and discharge of mucus from goblet cells in the trachea. Because these changes are similar to those that occur after allergen challenge in human asthma, we suggest that this represents a useful animal model in which to study the mechanism of early and late bronchoconstriction responses.

Journal ArticleDOI
TL;DR: Right heart catheterization was performed in a series of 46 consecutive patients in whom OSAS was firmly diagnosed by whole-night polysomnography, and there was no significant correlation between Ppa and the apnea index, the lowest sleep SaO2, or the time spent in apnea.
Abstract: The frequency of daytime pulmonary hypertension (PH) in patients with obstructive sleep apnea syndrome (OSAS) has not been well established and its mechanisms are still under debate. We have thus performed right heart catheterization, in addition to standard spirography and arterial blood gas measurements, in a series of 46 consecutive patients in whom OSAS was firmly diagnosed by whole-night polysomnography. Only 9 of the 46 patients (20%) had PH defined by a mean resting pulmonary arterial pressure (Ppa) ⩾ 20 mm Hg. Among the patients withoutresting PH, 14 had exercising PH (defined by a Ppa > 30 mm Hg during 40-watt, steady-state exercise). Patients with resting PH differed from the others by a lower daytime PaO2 (60.8 ± 7.6 versus 76.2 ± 9.4 mm Hg; p < 0.001), a higher daytime PaCO2 (44.6 ± 4.2 versus 38.0 ± 4.0 mm Hg; p < 0.001), and lower VC and FEV1 (p < 0.001). There was no difference between the 2 groups with regard to apnea index (62 ± 34 versus 65 ± 40) or the lowest sleep SaO2 (59 ± 21 versus ...

Journal ArticleDOI
TL;DR: It is concluded that Pi and WA are constant in airways whether the smooth muscle is relaxed or contracted and that Pi can be used as a marker of airway size and, under controlled conditions, can beused to calculate the smooth Muscle Shortening present in a given airway.
Abstract: Previous studies from our laboratory suggest that the internal airway perimeter (Pi) defined by the folded epithelial surface remains constant as the airways narrow. To test this hypothesis, we treated adjacent slices of resected lung lobes with either theophylline or carbachol and determined the dimensions of the airways in these lung slices. Transverse sections of contracted (n = 58) and relaxed (n = 55) airways were used to measure the Pi defined by the epithelial surface, lumen area (Ai), external perimeter (Pe) defined by the outer edge of the smooth muscle layer, and the external area (Ae). Wall area (WA = Ae − Ai) was calculated. The frequency distribution of internal perimeters was not significantly different for the contracted and relaxed airways, and when the square root of wall area was plotted against Pi, the regression lines for the contracted and relaxed airways were almost identical. The “relaxed” external perimeter was calculated Per = , and the percentage of muscle shortening (PMS) was de...


Journal ArticleDOI
TL;DR: The data demonstrate that LTC4 and histamine are released into nasal secretions of aspirin-sensitive asthmatics with naso-ocular and bronchospastic reactions after ingestion of low doses of aspirin without a decrease in the levels of PGE2 and suggest that L TC4 and Histamine contribute to the naso,ocular and Bronchospastics symptoms characteristic of reactions to aspirin.
Abstract: The levels of leukotriene C4 (LTC4), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and histamine were measured in nasal lavage fluids obtained from aspirin-sensitive, desensitized aspirin-sensitive, and aspirin-insensitive asthmatics and normal volunteers before and after ingestion of aspirin. Increased levels of LTC4 and histamine were associated with significant decreases in the FEV1 for 3 of 4 aspirin-sensitive asthmatics who had both naso-ocular and bronchospastic reactions to aspirin. In contrast, no increase in LTC4 or histamine release was detected in aspirin-sensitive asthmatics who had only bronchospastic reactions to aspirin. No significant decreases in PGE2 levels or increases in LTB4 levels were detected during these reactions to relatively low doses of aspirin regardless of the clinical symptoms, nor was any increase in mediator release apparent in lavage fluids from normal donors, aspirin-insensitive asthmatics, and desensitized aspirin-sensitive subjects before or after various doses of aspirin. Levels of PGE2 decreased in nasal secretions from normal volunteers, aspirin-insensitive asthmatics, and desensitized aspirin-sensitive subjects after ingestion of 650 mg of aspirin. These decreases were not associated with increased LTC4 or LTB4 or with histamine release, decreased FEV1, or naso-ocular symptoms. In addition, reductions of PGE2 release were similar for normal and desensitized aspirin-sensitive volunteers (63 +/- 11 versus 61 +/- 10%, respectively). The data demonstrate that LTC4 and histamine are released into nasal secretions of aspirin-sensitive asthmatics with naso-ocular and bronchospastic reactions after ingestion of low doses of aspirin without a decrease in the levels of PGE2 and suggest that LTC4 and histamine contribute to the naso-ocular and bronchospastic symptoms characteristic of reactions to aspirin.