Citations

Abstract Intraluminal airway pressure and pharyngeal muscle activity are widely recognized as major determinants of the size and collapsibility of the upper airway. In addition, changes in the volume or pressure of tissue surrounding the pharyngeal airway may significantly influence its size. The present study used fast computed tomography (CT) to determine the effects of changes in central venous pressure (CVP) on upper airway size. Ten awake male patients with obstructive sleep apnea (OSA) were studied. Scans were performed at functional residual capacity (FRC) and at the end of a tidal inspiration (VTei) under three conditions of CVP: (1) at baseline (CVP nl) with patients lying supine; (2) at decreased CVP (CVP-) by inflating blood pressure cuffs to 40 mm Hg on both legs; and (3) at increased CVP (CVP+) by elevating both legs to 33 degrees. At FRC, changes in CVP had no significant effect on either mean or minimum cross-sectional area (CSA) of the upper airway. In contrast, an analysis of variance (ANOVA) indicated that alterations in CVP were associated with changes in mean CSA (p = 0.03) and to a lesser extent in minimum CSA (p = 0.07) at VTei. With the legs elevated (CVP+), neither mean nor minimum CSA showed any significant change with tidal breathing. However, after leg-cuff inflation (CVP-), highly significant increases in both mean (163 +/- 22 to 218 +/- 19 mm2, p = 0.001) and minimum (48 +/- 8 to 85 +/- 12 mm2, p = 0.02) CSA were detected. Changes in mean and minimum CSA with tidal breathing at baseline (CVP nl) were intermediate. These results indicate that changes in CVP significantly alter the response of the upper airway to tidal breathing. They further suggest that increases in upper airway size with tidal breathing may be related to reduction in venous blood volume in pharyngeal and neck tissues as the generation of negative intrathoracic pressure during inspiration increases venous return to the chest.

Abstract The early stage of idiopathic pulmonary fibrosis (IPF) is thought to involve a smaller number of alveoli and to be characterized predominantly by cellularity and minimal fibrosis, whereas advanced disease involves a large number of alveoli and is characterized predominantly by fibrosis with minimal cellularity. In addition, correlative studies have indicated that prognosis and response to therapy is determined in part by the extent of fibrosis and cellularity. This study was undertaken to determine whether pulmonary function assessment would help distinguish between the cellular and fibrotic phases of this disorder, as determined by a semiquantitative pathology scoring system that comprised four factor scores: fibrosis, cellularity, granulation/connective tissue, and desquamation. Ninety-six untreated patients with biopsy-confirmed IPF (27 never smokers, 32 current smokers, and 37 ex-smokers) were evaluated. In the group as a whole, there was no significant relationship between the fibrosis or the connective/granulation tissue factor scores and any of the physiologic parameters. The Dl co correlated with the “desquamation” and the total pathology scores, whereas the TLC and FVC correlated with the cellularity factor score. In the current smokers, the coefficient of elastic retraction, Dl co/Va, and FEV1/FVC ratio were significantly lower than in never smokers and ex-smokers, and TLC and FVC were higher than in never smokers. Also, the mean cellularity and granulation/connective tissue factor scores were significantly lower, and the desquamation factor score was significantly higher than those in never smokers and ex-smokers. Both age and smoking status were significant for the cellularity factor score, whereas for the connective/granulation tissue factor score, age was not significant but smoking status was. For the desquamation factor score, age was significant but smoking status was not. There were significant differences between never smokers and ever smokers in the relationship between the pathology factors and measurements of respiratory function, and this may explain some of the difficulty in assessing structure-function correlation in patients with IPF. In the never smokers, the correlations between structure and function were likely the direct result of IPF per se. In the current smokers, bronchiolar and/or emphysematous changes associated with cigarette smoking may have complicated the pathologic alterations caused by IPF, as well as influencing the functional derangements.

Abstract Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. We hypothesized that cytokine(s) produced in the disease sites are implicated in the pathophysiology of CEP. We studied peripheral blood and bronchoalveolar lavage fluids (BALF) obtained from two lung segments of a patient with CEP. Seventy times more eosinophils were found in the BALF from an involved lung segment (showing patchy opacification on a chest roentgenogram) than from an uninvolved segment. The eosinophil-active cytokines interleukin-5 (IL-5), IL-6, and IL-10 were strikingly elevated in the BALF from the involved lung segment, whereas no or minimal levels of these cytokines were detectable in the BALF from the uninvolved segment or serum, respectively. Leukocytes in the involved lung segment, but not those in peripheral blood, expressed messenger ribonucleic acid (mRNA) for IL-5, IL-6, and IL-10. In contrast, IL-2, IL-3, IL-4, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) were not detected in any sample. These findings suggest that increased production of several cytokines, such as IL-5, IL-6, and IL-10, in the involved lung segment, but not in the uninvolved lung segment or peripheral blood, is a critical pathophysiologic feature of CEP.

Abstract Ventilation was measured in 31 difficult-to-wean patients while pressure support (PS) was reduced by 5 cm H2O every 20 min. Weaning had to be aborted in 14 of 31 patients (Group F) because they met predefined distress criteria. The remaining 17 patients who were able to complete the "weaning test" (Group S) had larger static respiratory compliances (Cstat = 0.08 +/- 0.02 versus 0.05 +/- 0.01 L/cm H2O, p < or = 0.05) and a lower dead space to tidal volume ratio (0.55 +/- 0.05 versus 0.64 +/- 0.06, p < or = 0.05). Group S patients had a larger tidal volume (VT) than did those of Group F at most PS settings. The groups differed with respect to VT maintenance during PS withdrawal (p < 0.01). In Group S, VT fell exponentially with machine support and stabilized at PS levels between 5 and 10 cm H2O. In contrast, Group F patients defended VT at higher PS settings but were unable to maintain VT during distress. Ventilatory response parameters such as the rapid shallow breathing index were of limited value in predicting weaning outcome and yielded receiver operator curve area values between 0.66 and 0.82 over the range of PS settings tested. We conclude that the gradual withdrawal of machine support does not facilitate the recognition of impending respiratory failure.

Abstract Fast-CT scanning was used to study the effects of changes in body position on upper airway (UA) size and shape in 11 awake subjects with obstructive sleep apnea (OSA). Six patients with position (P)-dependent OSA were compared with five patients with nonposition (NP)-dependent OSA. Scans were repeated in the prone (PRN), right side (RS), and supine (SUP) body positions at both functional residual capacity and end-inspiratory tidal volume. Significant group, group by position, and borderline group by respiration effects were detected for minimum but not mean UA dimension data. Significant differences between groups were noted in minimum cross-sectional area and minimum lateral distance but not in minimum anteroposterior distance in the RS and SUP positions. Turning from the PRN to the RS or SUP position tended to decrease UA size in the NP group by decreasing the lateral distance, while the opposite effect was found in the P group. The results indicate that changes in body position during wakefulness affect the lateral but not the anteroposterior dimensions of the UA, and the UA behaves differently in patients with NP and P OSA in response to changes in body position.

Abstract This study was designed to characterize the clinical spectrum and course of tracheobronchial involvement in Wegener's granulomatosis (WG). Of the 51 patients with biopsy-proven WG who underwent bronchoscopy at least once at our institution between January 1982 and November 1993, 30 (59%) had endobronchial abnormalities due to WG. Initial findings included subglottic stenosis in five (17%), ulcerating tracheobronchitis with or without inflammatory pseudotumors in 18 (60%), tracheal or bronchial stenosis without inflammation in four (13%), and hemorrhage without identifiable source in two (4%) patients. Nine patients with ulcerating tracheobronchitis on initial study had subsequent bronchoscopies for continued symptoms, which in seven cases documented the progression from ulcerating tracheobronchitis to stenosis without inflammation. Bronchoscopic interventions included dilation by rigid bronchoscope in three, YAG-laser treatment in one, and placement of silastic airway stents in three patients. Only the stents provided persistent airway patency. Endobronchial biopsies were performed on 21 occasions in 17 patients. Half of the specimens were helpful in establishing the diagnosis and in all but three in assessing disease activity. While antineutrophil cytoplasmic antibody titers reflect overall disease activity, no correlation with endobronchial inflammatory activity was apparent.

Abstract Previous research has suggested that nicotine may be therapeutically useful in the treatment of sleep-disordered breathing. The development of transdermal nicotine delivery systems has allowed us to test the overnight effectiveness of nicotine. Twenty nonsmoking subjects (10 men, 10 women) were recruited on the basis of a history of habitual snoring that was confirmed by overnight laboratory monitoring. Subjects were then randomized (double-blind crossover design) to receive either placebo or an active patch that delivers 11 mg of nicotine over a 24-h period. Patches were applied at 6 P.M. and removed at 6 A.M. the following morning, at which time venous blood was obtained for determination of serum nicotine concentrations. Polysomnography was performed using standard techniques to assess sleep architecture and sleep-disordered breathing. Snoring was monitored with a sound-level meter and quantitatively analyzed to determine the snoring index (SI) (number of snores per hour of sleep) and mean and maximum snoring intensities. The age of the subjects was 46.9 +/- 11.4 yr (mean +/- SD) and their mean body mass index (BMI) 33.3 +/- 4.6 kg/m2. A mean nicotine level was nondetectable with placebo and 7.8 +/- 2.3 ng/ml with wearing of an active patch. Nicotine decreased total sleep time (TST) by 33 min (p < or 0.01), sleep efficiency from 89.7 to 83.5% (p < or = 0.01), and percent rapid eye movement (REM) sleep from 18.8 to 15.1% (p < or = 0.01), and prolonged initial sleep latency (ISL) from 6.7 to 18.2 min (p < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract The obese Zucker rat, an autosomally genetic model of obesity, represents a good model of relatively early onset human obesity. Although factors associated with the control of metabolism and thermoregulation have been studied extensively in these animals, pulmonary mechanics and ventilation have not been documented and form the basis of this investigation. Studies were carried out in 16 obese and 18 lean female littermates (698 +/- 79 versus 304 +/- 24 g, p < 0.001). Pulmonary function, including lung volumes and respiratory system compliance, was evaluated in supine anesthetized animals. With the exception of residual volume, all other lung volumes, including function residual capacity, total lung capacity, expiratory reserve volume, and inspiratory capacity, were significantly reduced (p < 0.05 or better) in the obese phenotype compared with volumes in the lean littermates. Pressure-volume relationships of the intact respiratory system and the excised lung were also determined. Although lung compliance was similar between the phenotypes, respiratory system compliance was significantly lower (0.85 +/- 0.06 versus 0.67 +/- 0.09 ml/cm H2O, p < 0.01) in the obese rats. Oxygen consumption and ventilatory parameters (including respiratory rate, tidal volume, minute ventilation, inspiratory time, and expiratory time) were similar between phenotypes breathing room air, and the minute ventilation in response to hypoxia was similar in both groups. In marked contrast, obese animals exhibited a blunted ventilatory response to hypercapnia (221 +/- 38 versus 135 +/- 44 ml/min, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract Segmental bronchoprovocation (SBP) with allergen was used in an attempt to study eosinophils recruited to the airway 24 h after challenge. Unexpectedly, in the first four patients, neutrophils (rather than eosinophils) were recruited in the bronchoalveolar lavage (BAL) fluids, and we hypothesized that the allergen extracts were contaminated with endotoxin. The extracts used for challenge in the first four patients tested positive for bacterial endotoxin in a limulus amebocyte lysate assay. Rechallenge of one patient from the first group with a comparable dose of an endotoxin-free extract and SBP with endotoxin-free extract in five additional patients resulted in preferential recruitment of eosinophils rather than neutrophils. The number of neutrophils recovered from the challenged segments in the patients challenged with endotoxin-free extract was significantly less than that observed in the first four patients. Taken together, these observations suggest that neutrophil recruitment in the 24-h BAL fluids from the first four patients was probably due to endotoxin contamination of the allergen extract. We caution investigators that endotoxin contamination of allergen extract may alter the cellular inflammation during the late airway response following allergen challenge.

Abstract The present study sought to examine the effects of aging on the isometric contractile and fatigue properties as well as the myosin heavy chain (MCH) isoform composition of the rat diaphragm muscle. Male Fischer 344 (F344) specific pathogen-free rats 6 and 24 mo old were used in the study. Peak twitch force was approximately 23% lower (p < 0.05) in the senescent diaphragm compared with the young. Time to peak twitch force and one-half relaxation time of twitch force did not differ between groups. There was a significant decrease (15 to 18%, p < 0.05) in the specific force (N/cm2) of the senescent diaphragm at all stimulation frequencies (10 to 100 Hz) examined. In addition, the fatigability of the diaphragm did not significantly differ between the two groups. No significant changes in the distribution of MHC 1 and 2A isoforms were observed with aging. However, the contribution of MHC 2X significantly decreased with senescence (young, 37.5%; senescent, 30.5%), whereas the contribution of MHC 2B in the senescent diaphragm was significantly higher (young, 6.5%; senescent, 15.0%; p < 0.05). We conclude that the age-related decline in diaphragm muscle specific force is caused by intrinsic factors other than changes in MHC composition.