Showing papers in "The American review of respiratory disease in 1993"

Objective Measurement of Patterns of Nasal CPAP Use by Patients with Obstructive Sleep Apnea

Abstract: Obstruction of the upper airway during sleep (OSAS) is widely treated by having patients self-administer nasal continuous positive airway pressure (CPAP). To obtain objective evidence of the patterns of CPAP use, information was gathered from two urban sites on 35 OSAS patients who were prescribed CPAP for a total of 3,743 days. Patients were given CPAP machines that contained a microprocessor and monitor that measured actual pressure at the mask for every minute of each 24-h day for an average of 106 days per patient. They were not aware of the monitor inside the CPAP machines. Monitor output was compared with patients' diagnostic status, pretreatment clinical and demographic characteristics, and follow-up self-reports of CPAP use, problems, side effects, and aspects of daytime fatigue and sleepiness. Patients attempted to use CPAP an average of 66 +/- 37% of the days monitored. When CPAP was used, the mean duration of use was 4.88 +/- 1.97 h. However, patients' reports of the duration of CPAP use overestimated actual use by 69 +/- 110 min (p < 0.002). Both frequency and duration of CPAP use in the first month reliably predicted use in the third month (p < 0.0001). Although the majority (60%) of patients claimed to use CPAP nightly, only 16 of 35 (46%) met criteria for regular use, defined by at least 4 h of CPAP administered on 70% of the days monitored. Relative to less regular users, these 16 patients had more years of education (p = 0.05), and were more likely to work in professional occupations.(ABSTRACT TRUNCATED AT 250 WORDS)

Measuring Quality of Life in Asthma

Abstract: The aim of this study was to evaluate the measurement properties of an Asthma Quality of Life Questionnaire. The study design was an 8-wk unblinded single cohort with assessments at 0, 4, and 8 wk. Thirty-nine adults with symptomatic asthma and a wide range of airway responsiveness and medication requirements were enrolled from previous studies and through notices in the local media. Those with inadequately controlled asthma were offered an inhaled steroid (budesonide). Asthma Quality of Life Questionnaire, spirometry, a clinical asthma control questionnaire, medication requirements, airway responsiveness to methacholine, the Sickness Impact Profile, and the Rand questionnaire were recorded at each visit. Patients kept daily diaries of peak flow rates and medications. The Asthma Quality of Life Questionnaire was able to detect changes in patients who responded to treatment or who had natural fluctuations in their asthma (p < 0.001) and to differentiate these patients from those who remained stable (p < 0.001). The Questionnaire was reproducible in patients who were stable (intraclass correlation coefficient = 0.92). There were significant longitudinal and cross-sectional correlations between asthma quality of life and other measures of both clinical asthma and generic quality of life. We conclude that the Asthma Quality of Life Questionnaire has good measurement properties and that it is valid as both an evaluative and a discriminative instrument. It measures the component of asthma most important to patients, and it should be considered for inclusion in all asthma studies.

The structure of large and small airways in nonfatal and fatal asthma

Abstract: Asthma is characterized by excessive airway narrowing and airway wall inflammation. In cases of fatal asthma, increased thickness of the airway wall is observed and may account for excessive airway narrowing when smooth muscle contracts. This study was undertaken to examine airway dimensions in large and small airways in both fatal and nonfatal cases of asthma. Airway wall areas (total, inner, and outer relative to smooth muscle layer), epithelial integrity, smooth muscle shortening, and the areas of smooth muscle, cartilage, and mucous glands were compared in transverse sections of large and small airways of subjects dying of asthma (fatal asthma, n = 11), those dying suddenly of nonrespiratory diseases and having a definite history of asthma (nonfatal asthma, n = 13), and those dying suddenly without any history of respiratory illness (control, n = 11). Airways were grouped by size using the basement membrane perimeter for comparison. All areas were expressed as areas per millimeter of basement membrane...

Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation.

Abstract: Prevalence and characteristics of nutritional depletion were established by body composition measurements in 255 COPD patients in stable clinical condition admitted to a pulmonary rehabilitation center. Depletion of body weight, fat-free mass (using bioelectrical resistance measurements), and muscle mass [from creatinine height index (CHI) and midarm muscle circumference] was most pronounced (40 to 50%) in patients suffering from chronic hypoxemia and in normoxemic patients with severe airflow obstruction (FEV1 < 35%) but also occurred in +/- 25% of patients with moderate airflow obstruction. Classification of the patients in four groups by body weight and fat-free mass revealed that depletion of fat-free mass may occur in normal-weight COPD patients (Group 3). These patients also exhibit a decreased CHI (61 +/- 21%, mean +/- SD) and suffer from physical impairment (12-min walking distance, WD, 532 +/- 152 m) to an even greater degree than underweight patients with relative preservation of fat-free mass (Group 2) (CHI = 73 +/- 16%; WD = 744 +/- 233 m). No systematic differences were established between the four groups in serum protein concentrations or medication use. We conclude that fat-free mass is a better indicator of body mass depletion than body weight. Classification of COPD patients by body weight and fat-free mass may have consequences for planning and interpretation of intervention strategies, particularly in Group 2 and 3 patients.

Particulate Air Pollution and Hospital Emergency Room Visits for Asthma in Seattle

Abstract: Recent studies have associated short-term exposure to respirable particulate matter (PM10) exposure with peak flow decrements, increased symptoms of respiratory irritation, increased use of asthma medications, and increased hospitalization for asthma. Increased mortality from chronic respiratory disease has also been reported. To help confirm whether PM10 exposure is a risk factor for the exacerbation of asthma, we compiled daily records of asthma emergency room visits from eight hospitals in the Seattle area. In Poisson regressions controlling for weather, season, time trends, age, hospital, and day of the week, the daily counts of emergency room visits for persons under age 65 were significantly associated with PM10 exposure on the previous day. The mean of the previous 4 days' PM10 was a better predictor (p < 0.005). The relative risk for a 30 µg/m3 increase in PM10 was 1.12 (95% confidence interval 1.20 to 1.04). Daily PM10 concentrations never exceeded 70% of the current ambient air quality standards...

Cellular Hypertrophy and Hyperplasia of Airway Smooth Muscles Underlying Bronchial Asthma: A 3-D Morphometric Study

Abstract: In order to study whether hyperplasia or hypertrophy of cells is responsible for the thickening of airway muscles, 3-D morphometry of airway muscle cells was performed on resin-embedded semithin serial sections of autopsied lungs from 10 asthmatics and five control subjects. There were five Type I and five Type II asthmatic lungs, as defined in an earlier study, thickened muscles being found only in the central bronchi in Type I and distributed over the whole airway tree in Type II. The analysis was based on "unbiased" 3-D morphometry to obtain the numerical density NV of muscle cells using a "disector," a spatial probe introduced by Sterio in 1984, which we modified into a stack of serial sections. The mean number NL of cells per unit airway length and the mean volume Vc of a single muscle cell were also determined. In Type I asthmatics, the number of cells increased in the larger bronchi unaccompanied by cellular hypertrophy at any level of the airway tree. In contrast, in Type II asthmatics, hypertrophy was shown to prevail over the whole airway, but it was most remarkable in the bronchioles, whereas hyperplasia was mild and localized only in the bronchi. The two types of asthmatic lungs may therefore result from different pathogeneses.

Small airways dimensions in asthma and in chronic obstructive pulmonary disease.

Abstract: The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of the Manifestations of Tuberculosis to CD4 Cell Counts in Patients with Human Immunodeficiency Virus Infection

Abstract: To evaluate the relationship between the clinical presentation of tuberculosis and the CD4 cell count in patients with human immunodeficiency virus (HIV) infection, we evaluated clinical and laboratory features of 97 HIV-infected patients with tuberculosis in whom CD4 cell counts were available. Extrapulmonary tuberculosis was found in 30 (70%) of 43 patients with 300 CD4 cells/microL (p = 0.02). Mycobacteremia was found in 18 (49%) of 37 patients with 300 CD4 cells/microL (p = 0.002). Acid-fast smears were more often positive in patients with low CD4 cell counts. Positive tuberculin skin tests were more common in patients with high CD4 counts. On chest roentgenograms, mediastinal adenopathy was noted in 20 (34%) of 58 patients with 200 CD4 cells/microL (p = 0.04). Pleural effusions were noted in six (10%) of 58 patients with 200 CD4 cells/microL (p = 0.04). The CD8 cell counts did not correlate with the manifestations of tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sudden-Onset Fatal Asthma: A Distinct Entity with Few Eosinophils and Relatively More Neutrophils in the Airway Submucosa?

Abstract: To determine the histologic differences in the airways of patients who died from sudden-onset asthma and the more common slow-onset asthma, we studied seven cases of fatal asthma. The numbers of eosinophils and neutrophils, as well as extracellular deposition of their respective granule contents in the airway mucosa and submucosa, were determined and statistically analyzed. Four of the seven patients had slow-onset asthma attacks in which the time interval between onset of asthma and death was more than 2.5 h. In contrast, three patients had sudden-onset asthma in which the time interval between onset of asthma attack and death was less than 1 h. The four patients with slow-onset fatal asthma had more eosinophils (34.1 +/- 6.3 in slow-onset; 9.7 +/- 3.5 in sudden-onset; p = 0.002) and fewer neutrophils (4.8 +/- 2.0 in slow-onset; 16.8 +/- 5.4 in sudden-onset; p = 0.008) in the airway submucosa than did patients with sudden-onset fatal asthma. In addition, within the slow-onset fatal asthma group, eosinophils exceeded neutrophils in the airway submucosa (eosinophils > neutrophils, p = 0.002). By contrast, within the sudden-onset fatal asthma group, neutrophils exceeded eosinophils (neutrophils > eosinophils, p = 0.04). We suggest that sudden-onset fatal asthma is immunohistologically distinct from slow-onset fatal asthma and that it is characterized by a relative paucity of eosinophils in the face of an excess of neutrophils in the airway submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Surfactant and the Adult Respiratory Distress Syndrome

Abstract: ARDS includes a complex series of events leading to alveolar damage, high permeability pulmonary edema, and respiratory failure. The endogenous pulmonary surfactant system is crucial to maintaining normal lung function, and only recently has it been appreciated that alterations in the surfactant system significantly contributed to the pathophysiology of the lung injury of patients with ARDS. Through a combination of analyzing BAL samples from patients with ARDS and extensive animal studies, there have been significant insights into the variety of surfactant abnormalities that can occur in injured lungs. These include altered surfactant composition and pool sizes, abnormal surfactant metabolism, and inactivation of alveolar surfactant by serum proteins present within the airspace. Positive effects of exogenous surfactant administration on acute lung injury have been reported. There is now a prospective, randomized clinical trial evaluating the efficacy of aerosolized exogenous surfactant in patients with ARDS. This trial has demonstrated improvements in gas exchange and a trend toward decreased mortality in response to the surfactant. Despite these encouraging results, there are multiple factors requiring further investigation in the development of optimal surfactant treatment strategies for patients with ARDS. Such factors include the development of optimal surfactant delivery techniques, determining the ideal time for surfactant administration during the course of injury, and the development of optimal exogenous surfactant preparations that will be used to treat these patients. With further clinical trials and continued research efforts, exogenous surfactant administration should play a useful role in the future therapeutic approach to patients with ARDS.

Airway Mucosal Inflammation Even in Patients with Newly Diagnosed Asthma

Abstract: We have studied bronchial biopsies from 14 patients with newly diagnosed asthma (four men and 10 women), who had had asthma symptoms, on average, 74 months (range, 2 to 12 months) and from four control subjects The patients had not received corticosteroids, disodium cromoglycate, or theophylline before the study The bronchial biopsies were taken, using a rigid-tube bronchoscope under local anaesthesia, from two different airway levels: (1) inside the right upper lobe bronchus, and (2) at the opening of the right middle lobe The specimens were prepared for both light and electron microscopy The use of Slot grids 1 x 2 mm enabled a large area of the thin sections to be photographed and analyzed by applying a graphic Autocad program There was an increase in the numbers of mast cells (p < 0001), eosinophils (p < 005), lymphocytes (p < 005), and macrophages (p < 005) in the epithelium of patients with newly diagnosed asthma as compared with those in control subjects In the lamina propria, these asthmatic patients had more eosinophils (p < 0001), lymphocytes (p < 0001), macrophages (p < 0001), and plasma cells (p < 0001) than did the control subjects We conclude that, in asthma, an airway inflammatory process is present even at a clinically early stage of the disease In the asthmatic airways, there are signs of a general inflammatory response caused by more than one cell type

Exertional Breathlessness in Patients with Chronic Airflow Limitation The Role of Lung Hyperinflation

Abstract: There is considerable intersubject variability in the perceived intensity of breathlessness for a given level of activity among patients with chronic airflow limitation (CAL). To examine possible factors contributing to this variability we compared breathing pattern parameters, dynamic operational lung volumes, and Borg dyspnea ratings in 23 patients with severe CAL and in 10 healthy age-matched normal subjects during cycle ergometry to symptom-limitation. Patients with CAL had significantly (p < 0.01) higher levels of ventilation (% maximal voluntary ventilation) for a given work rate (slope of VE(%MVV)/WR(% pred max) = 1.51 +/- 0.18 versus 0.63 +/- 0.10; mean +/- SEM) and greater dynamic lung hyperinflation (DH) (change [delta] in end-expiratory lung volume [EELVdyn] = +0.31 +/- 0.11 L versus -0.16 +/- 0.22 L). Compared with normal subjects at a standardized VE (30 L/min), the CAL group was more breathless Borg = 4 +/- 1 versus 2 +/- 1, p < 0.01) and hyperinflated (EELVdyn = 75 +/- 3 versus 46 +/- 6% TLC, p < 0.001; end-inspiratory lung volume [EILVdyn] = 85 +/- 3 versus 67 +/- 5% TLC, p < 0.01). Within the CAL group, change in Borg ratings correlated with delta VE(%MVV) (r = 0.77, p < 0.001) and with slope of VE(%MVV)/WR(% pred max) (r = 0.48, p < 0.01). Regression analysis selected delta EILVdyn (or delta inspiratory reserve volume [delta IRVdyn]) from various dynamic ventilatory parameters as the strongest predictor of delta Borg (r = 0.63, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Tidal Volume, FRC, and End-inspiratory Volume in the Development of Pulmonary Edema following Mechanical Ventilation

Abstract: Mechanical ventilation with high peak inspiratory pressure and large tidal volume (VT) produces permeability pulmonary edema. Whether it is mean or peak inspiratory pressure (i.e., mean or end-inspiratory volume) that is the major determinant of ventilation-induced lung injury is unsettled. Rats were ventilated with increasing tidal volumes starting from different degrees of FRC that were set by increasing end-expiratory pressure during positive-pressure ventilation. Pulmonary edema was assessed by the measurement of extravascular lung water content. The importance of permeability alterations was evaluated by measurement of dry lung weight and determination of albumin distribution space. Pulmonary edema with permeability alterations occurred regardless of the value of positive end-expiratory pressure (PEEP), provided the increase in VT was large enough. Similarly, edema occurred even during normal VT ventilation provided the increase in PEEP was large enough. Furthermore, moderate increases in VT or PEEP that were innocuous when applied alone, produced edema when combined. The effect of PEEP was not the consequence of raised airway pressure but of the increase in FRC since similar observations were made in animals ventilated with negative inspiratory pressure. However, although permeability alterations were similar, edema was less marked in animals ventilated with PEEP than in those ventilated with zero end-expiratory pressure (ZEEP) with the same end-inspiratory pressure. This "beneficial" effect of PEEP was probably the consequence of hemodynamic alterations. Indeed, infusion of dopamine to correct the drop in systemic arterial pressure that occurred during PEEP ventilation resulted in a significant increase in pulmonary edema. In conclusion, rather than VT or FRC value, the end-inspiratory volume is probably the main determinant of ventilation-induced edema. Hemodynamic status plays an important role in modulating the amount of edema during lung overinflation but does not fundamentally modify the characteristics of this edema which is consistently associated with major permeability alterations. These results may be relevant for ventilatory strategies during acute respiratory failure.

Clinical features of pulmonary disease caused by rapidly growing mycobacteria. An analysis of 154 patients

Abstract: The role of rapidly growing mycobacteria (RGM) as pulmonary pathogens has been unclear. We identified 154 cases of lung disease caused by RGM using the microbiologic and radiographic criteria of the American Thoracic Society (ATS) and availability of the causative organism for study. More than one third of patients had positive lung biopsy cultures. Patients were predominately white (83%), female (65%) nonsmokers (66%), and they had prolonged periods from onset of symptoms to diagnosis of their disease. Cough was an almost universal presenting symptom, whereas constitutional symptoms became more important with progression of disease. Upper lobe infiltrates were most common (88%), with 77% of patients developing bilateral disease. Cavitation was present in only 16% of the patients. Specific underlying diseases were infrequent, but they included previously treated mycobacterial disease (18%), coexistent Mycobacterium avium complex (8%), cystic fibrosis (6%), and gastroesophageal disorders with chronic vomit...

Dynamic Upper Airway Imaging during Awake Respiration in Normal Subjects and Patients with Sleep Disordered Breathing

Abstract: The effects of respiration on upper airway caliber were studied using cine computed tomography (CT) in 15 normal subjects, 14 snorer/mildly apneic subjects, and 13 patients with obstructive sleep apnea. All subjects were scanned in the supine position during awake nasal breathing. Eight-millimeter-thick axial slices were obtained at four anatomic levels from the nasopharynx to the retroglossal region every 0.4 s during a respiratory cycle. Tidal volume measured from an integrated pneumotachograph signal was correlated with slice acquisition during inspiration and expiration to generate loops comparing upper airway area and tidal volume. In all three subject groups and at all anatomic levels studied, there were significant dimensional changes in upper airway caliber during the respiratory cycle. The major findings in this investigation include: (1) the upper airway was significantly smaller in apneic than normal subjects, especially at the retropalatal low and retroglossal anatomic levels; in apneic patients the airway had an anterior-posterior configuration unlike the normal airway, which had a horizontal configuration with the major axis in the lateral direction; (2) in all three subject groups, little airway narrowing occurred in inspiration, suggesting that the action of the upper airway dilator muscles balanced the effects of negative intraluminal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitization and Exposure to Indoor Allergens as Risk Factors for Asthma among Patients Presenting to Hospital

Abstract: To investigate the role of indoor allergens in adult patients with acute asthma, we conducted a case-controlled study on patients presenting to an emergency room One hundred and fourteen patients and 114 control subjects were enrolled over a 1-yr period in Wilmington, Delaware Sera were assayed for total IgE, and for IgE antibodies to dust mites, cat dander, cockroach, grass pollen, and ragweed pollen Dust was obtained from 186 homes and assayed for dust mite, cat, and cockroach allergens IgE antibodies to mite, cat, and cockroach were each significantly associated with asthma, and this association was very strong among participants without medical insurance and among African Americans Among 99 uninsured participants, sensitization to one of the indoor allergens (> 200 RAST units) was present in 28 of 57 asthmatics and in one of 42 control subjects (odds ratio, 39; confidence interval, 94 to 166) For cat and cockroach the combination of sensitization and presence of allergen in the house was significantly associated with asthma Furthermore, there was a strong inverse relationship between IgE antibodies to cat and to cockroach, and the risk of this sensitization was in large part restricted to homes or areas with high levels of allergen Thirty-eight percent of the asthmatics, but only 8% of the control subjects, were allergic to one of the three indoor allergens, and had high levels of the relevant allergen in their houses (odds ratio, 74; confidence interval, 33 to 165)(ABSTRACT TRUNCATED AT 250 WORDS)

When tuberculosis treatment fails : a social behavioral account of patient adherence

Abstract: Several conclusions about measuring adherence can be drawn. Probably the best approach is to use multiple measures, including some combination of urine assays, pill counts, and detailed patient interviews. Careful monitoring of patient behavior early in the regimen will help predict whether adherence is likely to be a problem. Microelectronic devices in pill boxes or bottle caps have been used for measuring adherence among patients with tuberculosis, but their effectiveness has not been established. The use of these devices may be particularly troublesome for some groups such as the elderly, or precluded for those whose life styles might interfere with their use such as the homeless or migrant farm workers. Carefully designed patient interviews should be tested to determine whether they can be used to predict adherence. Probably the best predictor of adherence is the patient's previous history of adherence. However, adherence is not a personality trait, but a task-specific behavior. For example, someone who misses many doses of antituberculosis medication may successfully use prescribed eye drops or follow dietary recommendations. Providers need to monitor adherence to antituberculosis medications early in treatment in order to anticipate future problems and to ask patients about specific adherence tasks. Ongoing monitoring is essential for patients taking medicine for active tuberculosis. These patients typically feel well after a few weeks and either may believe that the drugs are no longer necessary or may forget to take medication because there are no longer physical cues of illness. Demographic factors, though easy to measure, do not predict adherence well. Tending to be surrogates for other causal factors, they are not amenable to interventions for behavior change. Placing emphasis on demographic characteristics may lead to discriminatory practices. Patients with social support networks have been more adherent in some studies, and patients who believe in the seriousness of their problems with tuberculosis are more likely to be adherent. Additional research on adherence predictors is needed, but it should reflect the complexity of the problem. This research requires a theory-based approach, which has been essentially missing from studies on adherence and tuberculosis. Research also needs to target predictors for specific groups of patients. There is clear evidence of the effect on adherence of culturally influenced beliefs and attitudes about tuberculosis and its treatment. Cultural factors are associated with misinformation about the medical aspects of the disease and the stigmatization of persons with tuberculosis. Culturally sensitive, targeted information is needed, and some has been developed by local tuberculosis programs.(ABSTRACT TRUNCATED AT 400 WORDS)

Cellular and Biochemical Analysis of Induced Sputum from Asthmatic and from Healthy Subjects

Abstract: To determine the feasibility of cellular and biochemical analysis of sputum induced after inhalation of hypertonic (3%) saline, we analyzed sputum induced in 10 healthy and in 18 asthmatic subjects. We also analyzed saliva samples from all subjects. The entire sputum sample and the saliva sample were reduced using dithiothreitol, and cell counts and differentials were determined. Biochemical analysis was performed on sputum and saliva supernatants obtained after centrifugation. We found that induced sputum from asthmatic subjects had a higher percentage of eosinophils [8.1 +/- 3.43 (mean +/- SEM) versus 0.03 +/- 0.02%, p < 0.009] (after excluding squamous cells) and also had higher levels of albumin (232.3 +/- 54.8 versus 79.5 +/- 9.7 micrograms/ml, p < 0.02), fibrinogen (44.2 +/- 11.6 versus 11.9 +/- 2.5 micrograms/ml, p < 0.008) and eosinophil cationic protein (ECP) (142.6 +/- 34.2 versus 26.1 +/- 4.7 ng/ml, p < 0.006) but not of histamine or tryptase. In saliva, squamous cells made up more than 99% of the cells in both groups, and protein concentrations were not significantly different. We conclude that cellular and biochemical analysis of induced sputum is feasible in healthy and in asthmatic subjects and that it reveals differences similar to those reported from analyses of bronchial lavage fluid.

Pharyngeal Fat in Obstructive Sleep Apnea

Abstract: Although most patients with obstructive sleep apnea (OSA) are obese, it is not known how obesity contributes to airway collapse during sleep. The purpose of this study was to determine whether the volume of adipose tissue adjacent to the pharyngeal airway in humans is related to the degree of OSA. We studied 30 subjects, nine without OSA and 21 with OSA; two subjects were studied before and after weight loss. Adipose tissue was detected with magnetic resonance imaging using T1-weighted spin echo sequences. The volume of adipose tissue adjacent to the upper airway was determined by measuring the volume of all pixels in the intensity range of adipose tissue within the region bounded by the ramus of the mandible, the spine, the anterior border of the soft palate, and the hard palate. Polysomnography was performed with conventional techniques. All subjects had a collection of adipose tissue adjacent to the upper airway; the volume of this adipose tissue correlated with the number of apneas plus hypopneas per hour of sleep (r = 0.59, p < 0.001). Both patients who lost weight and had fewer apneas and hypopneas had a marked decrease in the pharyngeal adipose tissue volume. We conclude that adipose tissue is deposited adjacent to the pharyngeal airway in patients with OSA and that the volume of this tissue is related to the presence and degree of OSA.

Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure.

Abstract: Periodic breathing with central apneas during sleep is typically triggered by hypocapnia resulting from hyperventilation. We therefore hypothesized that hypocapnia would be an important determinant of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with congestive heart failure (CHF). To test this hypothesis, 24 male patients with CHF underwent overnight polysomnography during which transcutaneous PCO2 (PtcCO2) was measured. Lung to ear circulation time (LECT), derived from an ear oximeter as an estimate of circulatory delay, and CSR-CSA cycle length were determined. Patients were divided into a CSR-CSA group (n = 12, mean ± SEM of 49.2 ± 6.3 central apneas and hypopneas per h sleep) and a control group without CSR-CSA (n = 12, 4.9 ± 0.8 central apneas and hypopneas per h sleep). There were no significant differences in left ventricular ejection fraction, awake PaO2, mean nocturnal SaO2, or LECT between the two groups. In contrast, the awake PaCO2 and mean sleep PtcCO2 were signif...

Effects of One Night without Nasal CPAP Treatment on Sleep and Sleepiness in Patients with Obstructive Sleep Apnea

Abstract: Nasal continuous positive airway pressure (CPAP) has become the nonsurgical treatment of choice for obstructive sleep apnea syndrome (OSAS). Recent evidence suggests that intermittent use of CPAP by patients is more common than nightly compliance. To determine the consequences of intermittent CPAP use, in terms of a return of sleep-disordered breathing and daytime hypersomnolence, 15 OSAS subjects were evaluated at three times: (1) before CPAP treatment (pretreatment), (2) after 30 to 237 days posttreatment during a night of CPAP use (on CPAP), and (3) during a night without CPAP (off CPAP). Evaluations of sleep-disordered breathing and three domains of hypersomnolence, physiologic sleep tendency, subjective sleepiness, and performance, were accomplished with the respiratory disturbance index (RDI), multiple sleep latency test (MSLT), Stanford sleepiness scale (SSS), and psychomotor vigilance task (PVT), respectively. CPAP use was encouraged and monitored from pretreatment to post-treatment by daily diari...

The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin.

Abstract: A subset of persons with asthma develop bronchospasm, naso-ocular, gastrointestinal, and/or dermal reactions after ingesting aspirin (ASA) or agents with the capacity to inhibit cyclooxygenase. The bronchopulmonary reactions have been associated with a rise in urinary LTE4. We examined the effects of an inhibitor of 5-lipoxygenase, zileuton, in a group of eight asthmatic patients with known sensitivity to ASA accompanied by LTE4 hyperexcretion. We first confirmed ASA sensitivity and an increase in urinary LTE4 after ASA ingestion in these patients using a placebo-controlled ASA challenge. Subjects were then randomized to a double-blind, crossover trial to examine the effects of zileuton versus placebo on the response to ASA. Zileuton treatment decreased baseline urinary LTE4 excretion from a mean of 469 ± 141 pg/mg creatinine to 137 ± 69 pg/mg creatinine (p < 0.02) and blunted the maximum increase in urinary LTE4 after ingestion of ASA (3,539 ± 826 pg/mg creatinine versus 1,120 ± 316 pg/mg creatinine [p< ...

Activated T-Lymphocytes and Macrophages in Bronchial Mucosa of Subjects with Chronic Bronchitis

Abstract: To examine the nature and the degree of leukocyte infiltration and to determine the state of activation of cells in bronchial mucosa of subjects with chronic bronchitis, bronchoscopy was performed in 10 subjects with a history of cigarette smoking and chronic sputum production and in six normal nonsmoking control subjects. Lobar bronchial biopsies were examined using histochemical and immunohistochemical techniques. Subjects with chronic bronchitis had an increased number of total leukocytes (CD45 positive cells), both in the epithelium and in the lamina propria, than did the control subjects (p < 0.05), whereas the numbers of neutrophils, eosinophils, and mast cells were similar in the two groups. There was a significant increase in the numbers of macrophages (p < 0.01) and of T-lymphocytes (CD3 positive cells) (p < 0.05) in the lamina propria of chronic bronchitics, whereas the relative proportions of CD4 and CD8 positive cells were similar in the bronchitics and the control subjects. Subjects with chro...

Efficacy and safety of inhaled corticosteroids in asthma. Report of a workshop held in Eze, France, October 1992.

Abstract: Inhaled glucocorticosteroids have now become first-line therapy for the treatment of chronic asthma in many countries. They are the most effective asthma therapy currently available, and numerous studies have documented their long-term efficacy in asthma control in adults and in children. Inhaled steroids suppress inflammation in asthmatic airways, although their precise molecular mechanism of action is not yet certain. It is likely that steroids affect the transcription of several steroid-responsive genes, and, of particular importance, they may inhibit cytokine gene transcription and cytokine effects, thereby reducing the chronic inflammation in asthmatic airways. Inhaled steroids are now used at a much earlier stage in asthma therapy, and there is a strong argument for their early introduction in both adults and children to prevent asthma morbidity and mortality and possibly the structural changes resulting from uncontrolled chronic inflammation, which may lead to irreversible airflow obstruction in some patients. Of paramount importance is the question of safety as inhaled steroids are likely to be required for a long time. Local side effects caused by oropharyngeal deposition of the inhaled steroid may be reduced by the use of spacer devices and mouthwashing. Systemic side effects caused by gastrointestinal absorption of the fraction deposited in the oropharynx may also be reduced by these devices. There are differences in the systemic bioavailability of the different inhaled steroids currently in use, and inhaled steroids with the lowest bioavailability should be chosen when high doses of inhaled steroids are required for asthma control. Systemic side effects are usually observed only when daily doses of > 800 micrograms are inhaled, and whether effects on very sensitive biochemical indices are relevant to long-term deleterious effects is not yet certain. There is now overwhelming evidence that the doses of inhaled steroids required to control asthma in the majority of adults and children are safe and without systemic side effects. It is important to control asthma with the minimum dose of inhaled steroids possible, however. In the future it may be possible to develop inhaled steroids with even fewer systemic effects if the fraction absorbed from the respiratory tract can be rapidly metabolized in the bloodstream.

Adenosine in bronchoalveolar lavage fluid in asthma.

Abstract: The inhalation of nebulized adenosine causes bronchoconstriction in asthmatics. In order to explore whether endogenously produced adenosine may contribute to the pathophysiologic aspects of asthma, we measured adenosine concentrations in bronchoalveolar lavage (BAL) fluid in seven subjects with asthma, eight asymptomatic cigarette smokers, and eight normal subjects. The mean concentration of adenosine in BAL fluid from the normal subjects was 0.72 ± 0.16 µM. Subjects with asthma and cigarette smokers had significantly increased concentrations of adenosine in BAL fluid, 2.55 ± 0.50 and 1.89 ± 0.50 µM, respectively. Corrected for the dilution that occurs as a result of the lavage procedure, mean epithelial lining fluid adenosine concentrations were 60 ± 13 µM in normal subjects, 193 ± 58 µM in asthmatics, and 155 ± 56 µM in smokers. Adenosine concentrations were positively correlated with the protein content of the lavage fluid (r = 0.79). Inhalation of nebulized adenosine in the subjects with asthma provok...

Inhalation of Nitric Oxide Modulates Adult Human Bronchial Tone

Abstract: We studied whether nitric oxide (NO), added at 80 ppm to inspired gas, can exert a bronchodilatory effect in humans. Four groups were studied: (1) healthy adult volunteers (n = 6), (2) adult subjects with hyperreactive airways (n = 6) during provocation with inhaled methacholine (MCh), (3) patients with bronchial asthma (n = 13), and (4) patients with chronic obstructive pulmonary disease (COPD, n = 6). All subjects were studied in a body plethysmograph, measuring volume-corrected specific airway conductance (SGaw). No patient or volunteer reacted with bronchoconstriction during NO inhalation. Nitric oxide did not affect SGaw in healthy volunteers or in patients with COPD. Inhaled NO modulated the MCh-induced bronchoconstriction toward dilatation. In patients with bronchial asthma, SGaw increased (p < 0.05) from 0.4 +/- 0.1 to 0.6 +/- 0.2 (kPa.s)-1. In a succeeding test with inhalation of a beta 2-agonist immediately after NO inhalation, a more marked increase in SGaw was seen, to 1.2 +/- 0.3 (kPa.s)-1 (p < 0.001). We conclude that NO inhaled at 80 ppm has no effect on airway tone in healthy volunteers, but modulates the response to MCh provocation toward bronchodilation. It exerts a weak bronchodilatory effect in bronchial asthma, but not in COPD.

Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy

Abstract: Ozone (O3) is a major constituent of urban air pollution. The acute effects of the inhalation of O3 at ambient or near-ambient concentrations on bronchoalveolar lavage (BAL) end points consistent with a distal lung inflammatory response have been well documented in human subjects. Animal toxicologic studies have shown that the airway is also a major site of O3-induced injury and inflammation. To date, no studies have confirmed this finding in human subjects. Effects of O3 on the proximal airways are not adequately studied by BAL, which is primarily influenced by events occurring in the terminal bronchioles and alveoli. We hypothesized that O3 causes injury and inflammation in the airways in addition to that previously documented to occur in the distal lung. We performed isolated lavage of the left mainstem bronchus and forceps biopsy of the bronchial mucosa in a group of 14 healthy, athletic subjects 18 h after exposure to 0.20 ppm O3 for 4 h during moderate exercise in order to assess this possibility. W...

Idiopathic Pneumonia Syndrome after Bone Marrow Transplantation

Abstract: Introduced in the early 1970s for treatment of aplastic anemia and leukemia, bone marrow transplantation offers potentially effective treatment for a growing number of patients. The procedure is now recognized as therapeutic for an increasing number of diseases. Furthermore, advances in transplant immunobiology, supportive care, and prevention of graft-versus-host disease, coupled with the availability of suitable donors, make the technique both effective and feasible. In 1990 more than 5,500 patients received allogeneic marrow transplants from matched or partially matched family members, and more than 5,000 autologous transplant procedures were performed. The recent creation of the National Marrow Donor Program (NMDP), which currently lists more than 600,000 potential donors, has made identification of unrelated phenotypically HLA-identical donors possible for patients who do not have suitable donors among family members. It is estimated that more than 500 unrelated transplants will be performed in 1992....

Lung Function, Pre- and Post-natal Smoke Exposure, and Wheezing in the First Year of Life

Abstract: The relationship between initial level of lung function and subsequent wheezing, lower respiratory illness (LRI) was studied in 97 infants in whom the first measurement of pulmonary function (PFT) was made before 6 months of age. Occurrence of LRI was evaluated by standardized questionnaires at each well-baby visit, biweekly telephone calls to mothers, and review of all visits to physicians. Infant PFT was assessed by partial expiratory flow-volume curves and helium-dilution measurement of functional residual capacity (FRC). Maternal, prenatal smoking was assessed by urine cotinine and standard questionnaires. Infants who developed an LRI during the first year of life had lower preillness length-corrected forced expiratory flow at FRC (Vfrc) than those who did not experience an LRI (males, 2.06 ± 0.20 versus 2.32 ± 0.29 ml/s/cm; females, 2.38 ± 0.20 versus 2.91 ± 0.26 ml/s/cm). Similar results were observed with FRC-corrected Vfrc. No differences were observed for FRC. Differences in lung function were gr...