Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.     

Self-reported mental distress under the shifting daylight in the high north

Our knowledge of airways reactivity to inflammatory agonists is derived predominantly from tests dominated by large airway responsiveness. To determine directly, the histamine responsiveness of the smallest airways, eight normal and 11 asymptomatic asthmatic subjects were studied utilizing a wedged bronchoscope technique. A fiberoptic bronchoscope was wedged in the anterior segment of the right upper lobe and a double-lumen catheter was advanced through the working channel to its tip. With a constant flow of gas (5% CO2 in air) through one lumen of the catheter, pressure at the tip of the bronchoscope was measured with the subject breath-holding at FRC. Peripheral airways resistance (Rp) was measured at baseline and after saline, histamine (10, 50, 100 mg/ml) and isoproterenol (2 mg/ml) challenge through the bronchoscope. Baseline Rp of asthmatics (0.041 +/- 0.015 cm H2O/ml/min; mean +/- SE) was significantly greater than normal subjects (0.011 +/- 0.003 cm H2O/ml/min; p = 0.019). The log of the concentration of histamine that caused a 100% increase in peripheral airways response was greater in the normal subjects than in the asthmatic subjects (p = 0.0114) and correlated with whole lung responsiveness to histamine in asthmatics (r = 0.847, p < 0.05). Isoproterenol reversed completely the increase in Rp in normal subjects but not asthmatic subjects. The results of this study demonstrate that the resistance of the smallest peripheral airways, when measured directly, increased when challenged locally with histamine in both normal subjects and asthmatic subjects. However, the peripheral airways responsiveness was significantly enhanced in asthmatic subjects relative to normal controls.     

Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma

Oxidative stress contributes to airway inflammation and exhaled hydrogen peroxide (H2O2) and nitric oxide (NO) are elevated in asthmatic patients. We determined the concentrations of expired H2O2 and NO in 116 asthmatic (72 stable steroid-naive, 30 stable steroid-treated, and 14 severe steroid-treated unstable patients) and in 35 healthy subjects, and studied the relation between exhaled H2O2, NO, FEV1, airway responsiveness, and eosinophils in induced sputum. Both exhaled H2O2 and NO levels were elevated in steroid-naive asthmatic patients compared with normal subjects (0.72 +/- 0.06 versus 0.27 +/- 0.04 microM and 29 +/- 1.9 versus 6.5 +/- 0. 32 ppb, respectively; p < 0.001) and were reduced in stable steroid-treated patients (0.43 +/- 0.08 microM, p < 0.05, and 9.9 +/- 0.97 ppb, p < 0.001). In unstable steroid-treated asthmatics, however, H2O2 levels were increased, but exhaled NO levels were low (0.78 +/- 0.16 microM and 6.7 +/- 1.0 ppb, respectively). There was a correlation between expired H2O2, sputum eosinophils and airway hyperresponsiveness (methacholine PC20). Exhaled NO also correlated with sputum eosinophils, but not with airway hyperresponsiveness. Our findings indicate that measurement of expired H2O2 and NO in asthmatic patients provides complementary data for monitoring of disease activity.     

Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, including inflammatory epithelial cells. NO has been detected in the exhaled air of normal human subjects, and its concentration is raised in asthmatic patients. To study whether exhaled NO arises from the respiratory tract, we administered a NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA), by inhalation (490 mg) in a double-blind randomized manner in nine normal and six asthmatic subjects. Because exhaled NO may arise from an inducible isoform of NO synthase that may be inhibited by glucocorticosteroids, we also studied the effects of oral prednisolone (30 mg orally for 3 d) in seven normal and six asthmatic subjects in a separate double-blind crossover study with matched placebo. After nebulized L-NMMA, there was a significant fall in peak exhaled NO compared with saline control values, with a mean fall of 43.6 +/- 5.6% in normal subjects (p < 0.01) and of 39.7 +/- 6.5% (p < 0.01) in asthmatic subjects, which persisted for 4 h. There were no effects of L-NMMA inhalation on heart rate, blood pressure, or FEV1 in either normal or asthmatic patients. Administration of oral prednisolone (30 mg) resulted in a fall in exhaled NO concentrations in asthmatic subjects by 21.6 +/- 5.0% at 48 h (p < 0.01) but no significant change in normal subjects. These data suggest that NOS inhibitors may be safely given in normal and asthmatic patients and that the increased exhaled NO seen in asthmatic patients is likely to be caused by induction of inducible NOS.     

Functional characteristics of bronchial epithelium obtained by brushing from asthmatic and normal subjects

Airways epithelial cells may be involved in the pathogenesis of asthma, but their role remains to be determined. Epithelial cells can release large amounts of 15-hydroxy-eicosatetranoic acid (15-HETE) and smaller amounts of prostaglandin E2 (PGE2) as well as fibronectin, a mediator involved in epithelial repair after injury. Epithelial cells obtained after bronchial brushing of 16 asthmatic (age 38 +/- 5 yr) and 11 normal subjects (age 36 +/- 5 yr) were studied. The percentage of epithelial cells was assessed by immunocytochemistry using an anti-cytokeratin antibody. The viability of the cells was assessed by trypan blue exclusion. The release of 15-HETE PGE2 and fibronectin was studied in resting cells and after A23187 calcium ionophore stimulation. Epithelial cells always comprised more than 86% of cells recovered, and the viability of epithelial cells was significantly (p < 0.001, Mann-Whitney U test) greater in normal subjects (54 +/- 5%) compared with asthmatic subjects (13 +/- 1%). The release of 15-HETE and fibronectin by resting epithelial cells was significantly greater in asthmatics (p < 0.05, Mann-Whitney U test) than in normal subjects. A23187 significantly (p < 0.05, Wilcoxon W test) increased the release of 15-HETE and fibronectin. There was no significant difference in the release of PGE2 by resting cells from either asthmatics or normal subjects, but challenge with A23187 induced a significant (p < 0.03, Wilcoxon W test) increase in PGE2 from cells of asthmatics but not from cells of normal subjects. This study shows that epithelial cells are activated and less viable in asthma and suggests a role for these cells in asthma.     

Inauguration of Hospital del Salvador: its first fifty years

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. However, because direct measurement of endogenous NO has been difficult in vivo, the exact pathologic roles of NO in human airway inflammation have remained unclear. OBJECTIVE: This study was designed to determine whether NO may be harmful by amplifying allergic inflammation in asthmatic airways. METHODS: In this study we examined the concentration of stable end products of NO, nitrite and nitrate, in induced sputum in 18 patients with asthma and 10 normal control subjects and evaluated the relationship between levels of NO derivatives in sputum and cellular and biochemical profiles, the degree of airflow obstruction, and the cytotoxic activities for epithelial cells. RESULTS: The concentration of NO derivatives in induced sputum was significantly higher in patients with asthma than in normal control subjects (1086 +/- 325 mumol/L, 577 +/- 115 mumol/L; p < 0.05). Percentages of eosinophil counts and eosinophil cationic protein levels in sputum were also significantly higher in patients with asthma. Moreover, percentages of eosinophil counts and eosinophil cationic protein levels in sputum in patients with asthma were significantly correlated with the concentration of NO derivatives in sputum (r = 0.63, p < 0.01; r = 0.56, p < 0.05, respectively). In addition, we found that the concentration of NO derivatives in sputum in patients with asthma was significantly correlated with the degree of airflow obstruction (FEV1/forced vital capacity) (r = -0.62, p < 0.01) and with percentages of shedding epithelial cells (r = 0.61, p < 0.01). CONCLUSION: We have shown that a higher concentration of NO derivatives was found in induced sputum of patients with asthma as compared with normal subjects. The clinical implication of our findings is that measurement of NO derivatives in induced sputum may be useful for assessing allergic inflammation in airways.     

BAL neutrophilia in asthmatic patients. A by-product of eosinophil recruitment?

Although neutrophil number may be increased in the airways of patients with asthma, its pathogenetic role in this disorder remains unclear. We evaluated BAL of 8 normal control subjects, 30 +/- 2 years of age, and 24 patients with mild asthma: 17 patients with allergic asthma, 24 +/- 1 years of age, and 7 patients with nonallergic asthma, 30 +/- 1 years of age. The BAL of asthmatic patients showed increased numbers of neutrophils (p < 0.01), eosinophils (p < 0.01), and ciliated epithelial cells (p < 0.05) and increased concentrations of myeloperoxidase (MPO) (p < 0.01) compared with control subjects. Positive correlations were observed between the number of BAL neutrophils and eosinophils (Rs = 0.780, p < 0.0001) and between BAL neutrophil numbers and BAL MPO levels (Rs = 0.40, p < 0.05). No correlations were found between the following: (1) BAL eosinophils or neutrophils and BAL epithelial cells (p > 0.05, each comparison); (2) BAL neutrophils or eosinophils and log Pd15 methacholine (MCh) (p > 0.05, each comparison); or (3) BAL epithelial cells or log Pd15 MCh and BAL MPO (p > 0.05, each comparison). Dividing the patient population into two groups, allergic asthmatics and nonallergic asthmatics, similar BAL neutrophil, eosinophil, and epithelial cell numbers and similar MPO levels were found (p > 0.05, each comparison). In addition, the correlations between BAL neutrophils and eosinophils showed similar significance in the two patient subgroups (p > 0.05, each comparison). These results suggest that, both in allergic and nonallergic asthma, airway recruitment and activation of neutrophils occur as does parallel eosinophil migration. However, airway neutrophils do not seem to contribute significantly to epithelial cell injury or to airway hyperresponsiveness in the steady state.     

The advantages of the lateral decubitus position after spinal anesthesia with hyperbaric tetracaine

Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.     

Pharmacokinetics of ifosfamide administered according to three different schedules in metastatic soft tissue and bone sarcomas

We investigated whether an association exists between genetic variants of the human obesity (OB or leptin) gene and body mass index (BMI) or weight in subjects with Prader Willi syndrome (PWS) and in age- and gender-matched lean and obese subjects without PWS. The study included 51 subjects with PWS (mean age = 17.7 +/- 9.5 years, BMI = 29.7 +/- 8.3 kg/m2); 50 non-PWS obese subjects (mean age = 18.2 +/- 10.8 years, BMI = 33.3 +/- 9.5 kg/m2); and 53 non-PWS lean subjects (mean age = 17.8 +/- 9.5 years, BMI = 19.5 +/- 2.9 kg/m2). Allele sizes were determined via standard polymerase chain reaction of the D7S1875 locus, a dinucleotide repeat polymorphism close to the OB gene and classified as trichotomous (homozygous < 208 bp, heterozygous < 208/ > or = 208 bp, homozygous > or = 208 bp) or dichotomous (homozygous < 208 bp or not). Non-PWS males showed a marked decrease in weight with larger alleles while females did not (interaction effect, p < 0.05). Comparable effects were not observed among the PWS subjects. Associations between BMI and genotype were statistically significant (r = 0.22, one-tailed p < 0.05) and comparable to previous research among the non-PWS subjects < 18 years, but not the adults (r = 0.05, one-tailed p = 0.38). Correlations were not statistically significant among either the adult or non-adult PWS subjects.     

Distribution of asbestos bodies in the human lung as determined by bronchoalveolar lavage

Asbestos-related lung diseases tend to have distinct local distributions, for example, asbestosis first appears and tends to be more severe in the peripheral parts of the lower lung zones. The risk for asbestosis is related to the total asbestos burden of the lung. This suggests that the lower lobes in asbestos-exposed individuals may contain more asbestos than the other lobes. To test whether such topographic differences exist, we compared the number of retrieved asbestos bodies (AB) per ml BAL fluid in three groups of occupationally asbestos-exposed subjects who underwent BAL at different sampling sites. In Group 1 (n = 24) we performed BAL at three sites, namely in a segment of the right upper, right middle, and right lower lobe, to evaluate differences in asbestos body burden from lung apex to basis. There was a distinct increase in BAL asbestos body concentrations from the upper (21.2 +/- 9.1 AB/ml BAL fluid) to the middle (30.4 +/- 12.8 AB/ml BAL fluid) and to the lower lobe (56.0 +/- 20.2 AB/ml BAL fluid), all differences being significant (p < 0.01). In Group 2 (n = 40), we found good interlobar correlations for asbestos body counts between the right middle lobe (21.0 +/- 5.8 AB/ml BAL fluid) and the lingula (22.4 +/- 5.9 AB/ml BAL fluid) (r = 0.941, p < 0.001) and, in Group 3 (n = 15), between the ventral basal segment of the right (41.2 +/- 13.6 AB/ml BAL fluid) and left lung (39.0 +/- 13.6 AB/ml BAL fluid) (r = 0.966, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of coccal cell formation by Campylobacter jejuni using continuous culture techniques, and the importance of oxidative stress

OBJECTIVES: We tested the hypothesis that patients with incomplete systolic mitral leaflet closure (IMLC: apically displaced coaptation) also have restricted diastolic leaflet opening that is independent of mitral inflow volume and provides evidence supporting increased leaflet tethering. BACKGROUND: Competing hypotheses for functional mitral regurgitation (MR) with IMLC include global left ventricular (LV) dysfunction per se (reduced leaflet closing force) versus geometric distortion of the mitral apparatus by LV dilation (augmented leaflet tethering). These are inseparable in systole, but restricted leaflet motion has also been observed in diastole, and attributed to reduced mitral inflow. METHODS: Diastolic mitral leaflet excursion and orifice area were measured by two-dimensional echocardiography in 58 patients with global LV dysfunction, 36 with and 22 without IMLC, compared with 21 normal subjects. The biplane Simpson's method was used to calculate LV ejection volume, which equals mitral inflow volume in the absence of aortic regurgitation. RESULTS: The diastolic mitral leaflet excursion angle was markedly reduced in patients with IMLC compared with those without IMLC, whose ventricles were smaller, and normal subjects (17 +/- 10 degrees vs. 58 +/- 13 degrees vs. 67 +/- 8 degrees, p < 0.0001). Excursion angle was dissociated from mitral inflow volume (r2 = 0.04); excursion was reduced in patients with IMLC despite a normal inflow volume in the larger ventricles with MR (60 +/- 25 vs. 61 +/- 12 ml in normal subjects, p = NS), and excursion was nearly normal in patients without IMLC despite reduced inflow volume (40 +/- 10 ml, p < 0.001 vs. normal subjects). The anterior leaflet when maximally open coincided well with the line connecting its attachments to the anterior annulus and papillary muscle tip (angular difference = 3 +/- 7 degrees vs. 25 +/- 9 degrees vs. 32 +/- 10 degrees in patients with and without IMLC vs. normal subjects, p < 0.0001). In patients with IMLC, the leaflet tip orifice was smaller in an anteroposterior direction but wider than in the other groups, giving a normal total area (6.8 +/- 1.8 vs. 7.1 +/- 1.2 vs. 6.9 +/- 0.8 cm2, p = NS). CONCLUSIONS: Patients with LV dysfunction and systolic IMLC also have restricted diastolic leaflet excursion that is independent of inflow volume, coincides with the tethering line connecting the annulus and papillary muscle and reflects limitation of anterior motion relative to the posteriorly placed papillary muscles without a decrease in total orifice area. These observations are consistent with increased tethering by displaced mitral leaflet attachments in the dilated ventricles of patients with IMLC that can restrict both diastolic opening and systolic closure.     

Alteration of cardiovascular vagosympathetic control evaluated by spectral analysis of variations of heart rate and blood pressure in obesity

Several studies suggest alterations of parasympathetic and sympathetic control in obesity. We have already shown that more than 40% of non diabetic obese subjects have alterations of parasympathetic control of heart rate (HR) variations. The present study aimed to investigate parasympathetic and sympathetic cardiovascular control by using spectral analysis. Sixty-two non diabetic obese subjects were compared to 38 sex-matched healthy controls. Spectral analysis was performed by Anapres system and identified two particular peaks: the one of high frequency (0.20-0.25 Hz) for heart rate variations during controlled breathing which depends on parasympathetic activity, the other of low frequency (around 0.10 Hz) for systolic BP variations in the standing position which mainly depend on sympathetic activity. In control subjects the amplitude of the high frequency peak (r = -0.556, p < 0.0001) but not the amplitude of the low frequency peak correlated negatively with age. In the obese subjects both the high and low frequency peaks correlated negatively with age (r = -0.249; p = 0.05 and r = -0.289, p = 0.036 respectively) and did not correlate with body mass index. The high frequency peak was significantly lower than in controls (4.80 +/- 3.37 (SD) vs 8.38 +/- 4.14; p < 0.0001). In the 25 obese subjects over 40 years the low frequency peak was also significantly lower than in controls (10.00 +/- 3.10 vs 11.95 +/- 4.25; p < 0.05). This study suggests that 1) age must be taken into account when interpreting the cardiovascular parameters under vagosympathetic control; 2) in non diabetic obese subjects vagal activity is decreased and in those over 40 years sympathetic activity is also decreased.     

Treatment of recurrent corneal erosion using phototherapeutic keratectomy with the excimer laser

Tachyphylaxis to methacholine has been reported in nonasthmatic subjects. In a recent study on the prevalence of airway hyperresponsiveness (AHR) and atopy, we performed duplicate methacholine inhalation tests at a 60-min interval, in subjects with symptomatic asthma (n = 33), asymptomatic AHR (AAHR) (n = 72) and in a group of normal subjects (n = 130); 135/235 subjects were atopic. All subjects had a respiratory questionnaire, allergy skin prick tests, blood eosinophil counts and determination of total serum IgE level. In asthmatic subjects, PC20 just failed to be significantly higher on a second methacholine challenge (p = 0.09); when they were stratified according to severity of AHR and use of inhaled corticosteroids, we observed a significant increase in PC20 on the second test in asthmatic subjects with mild AHR not using corticosteroids (p < 0.01). In normal controls, PC20 methacholine was slightly increased on rechallenge (p < 0.01) as it was in those with AAHR (p < 0.01). There was no relationship between the magnitude of the change in PC20 and age, sex, baseline airway responsiveness, percent fall in FEV1 on the first challenge, atopic score, blood eosinophil counts and serum IgE levels. In conclusion, tachyphylaxis to methacholine is observed in normal or mild asthmatic subjects not using inhaled corticosteroids and in subjects with AAHR; however, in most subjects this change is of a small magnitude.     

Prevalence and correlates of echocardiographic determined left ventricular hypertrophy in 2318 asymptomatic middle-aged men: the ECCIS project. Epidemiolgia e Clinica della Cardiopatia Ischemica Silente

BACKGROUND: Serum levels of eosinophil cationic protein are an indirect measure of airway inflammation in asthma. It is proposed that the extent to which broncho-constriction or airway inflammation contributes to airflow obstruction in acute asthma may determine responsiveness to bronchodilator therapy. OBJECTIVE: To test the hypothesis that subjects with acute asthma exacerbations who respond poorly to inhaled bronchodilator treatment may have more marked airway inflammation than those who respond well to identical therapy. METHODS: Forty-eight asthmatic children who visited the emergency room due to acute exacerbations were studied. Serum levels of eosinophil cationic protein were measured at the time of acute exacerbations and of clinical remissions. At acute exacerbation, FEV1 was assessed before and after the administration of aerosolized salbutamol. RESULTS: The mean serum level of eosinophil cationic protein at acute exacerbation (41.1 +/- 12.8 micrograms/L) was significantly higher (P < .01) than that at clinical remission (30.0 +/- 8.5 micrograms/L) in the study population. The level at acute exacerbation was even higher in group A (n = 18: postbronchodilator FEV1 < 75% predicted) than in group B (n = 30: postbronchodilator FEV1 > or = 75% predicted), whereas both groups showed similar levels at clinical remission. The level at acute exacerbation correlated positively with severity of exacerbation (r = .47, P < .01) and negatively with bronchodilator responses (r = -.56, P < .01). This negative correlation was valid among subjects with a similar degree of exacerbation. CONCLUSION: A higher level of eosinophil cationic protein at acute asthma exacerbation was associated not only with more severe exacerbation but also with a lower degree of bronchodilator responsiveness. This suggests that degree of airway inflammation may be one determinant of degree of responsiveness to initial bronchodilator therapy at acute asthma exacerbation.     

Credibility of treatment in controlled trials of acupuncture

Total body water (TBW) was measured by deuterium oxide dilution (D2O) and predicted by bioelectric impedance analysis (BIA) (Deurenberg, Schouten, Andreoli and De Lorenzo 1993) in 21 subjects with Schistosoma mansoni infection and 17 healthy controls of similar age (32.8 +/- 13.7 years, n=38). Patients were selected to have no visible fluid retention and no cardiac or renal abnormalities. Body hydration (TBW per kg of body weight) was significantly higher in patients with schistosomiasis than in controls (62.9 +/- 3.6 vs 57.4 +/- 4.3%, p < 0.0005). A significant correlation was found between albumin levels and TBW% on the pooled sample (n=38; r=0.660, p < 0.0001). This relationship was not influenced by the presence of disease, as determined by ANCOVA. Values of TBW predicted by BIA were highly correlated and not significantly different (p=n.s., ANOVA) from those measured by D2O in both controls and patients (r=0.854, p < 0.001, SEE = 2.3 1, CV=5.9% and r=0.848, p < 0.001, SEE=4.0 1, CV=9.3%, respectively). The bias (TBW by BIA - TBW by D2O) was of 0.9 +/- 3.7 in controls and of -1.3 +/- 4.2 1 in patients. This bias was significantly correlated to TBW% in patients (r=0.575, p < 0.05) but not in controls (p=n.s.). It is concluded that subjects with schistosomiasis show an apparent subclinical increase in body hydration which could affect the prediction of TBW from BIA.     

Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial

STUDY OBJECTIVES: To determine whether obese, apparently healthy individuals experience dyspnea at rest and, if so, whether their pulmonary function test (PFT) profile and maximal respiratory pressures are different from obese, healthy subjects without dyspnea. DESIGN: Prospective, open. SETTING: Pulmonary function test laboratory, Veterans Administration Medical Center. PATIENTS: Twenty-three obese male subjects (each with a body mass index [BMI] of > 28 kg/m2) with an FEV1 level and an FEV1/FVC ratio > or = 80% of predicted and no coexisting conditions. Fifteen complained of dyspnea, where eight denied having it, at rest. MEASUREMENTS AND RESULTS: Standard PFT parameters and maximum static inspiratory (P(Imax)) and expiratory (P(Emax)) mouth pressures were determined. Subjects with dyspnea had similar age and height but larger body weight (113.9+/-5.0 vs 97.4+/-2.6 kg, p = 0.03) and BMI (37.4+/-1.6 vs 31.8+/-0.7 kg/m2, p = 0.02) than subjects without dyspnea, and a greater number of them were current or previous smokers. Forced expiratory flow at 75% vital capacity (54.9+/-6 vs 75.5+/-7% predicted, p = 0.05), maximum voluntary ventilation (MVV; 90.2+/-3.8 vs 107.8+/-9.3% predicted, p = 0.05), and P(Emax) (77+/-2 vs 97.8% predicted, p = 0.007) were significantly reduced in the group of subjects with dyspnea. Large airway function (FVC, FEV1, and FEV1/FVC ratio), lung volumes, and gas exchange parameters were similar between the two groups. CONCLUSIONS: Some obese, but otherwise healthy, individuals experience dyspnea at rest. Reduced P(Emax) and MVV combined with greater body mass and peripheral airway disease are most likely responsible for the sensation of dyspnea in these individuals.     

Effects of nasal continuous positive airway pressure therapy on respiratory parameters of upper airway patency in patients with obstructive sleep apnea syndrome

OBJECTIVES: To assess whether an initial treatment with nasal continuous positive airway pressure (NCPAP) therapy, applied for one night, had any effect on airway patency. METHODS: In 18 patients with obstructive sleep apnea syndrome (OSAS), we measured the total resistance of the respiratory system (Rrs) and their relevant lung functions before and after polysomnography, with and without NCPAP therapy. The Rrs was measured at 3 Hz with the forced oscillation technique. The overnight changes in the specific respiratory conductance (SGrs=reciprocal of the Rrs per unit lung volume) was also calculated in the sitting position. Since many reports have suggested that obesity, through fat deposits around the pharynx, can affect the mechanical and neuromuscular properties of the upper airway, we also investigated if the degree of obesity was related to the magnitude of improvement in these parameters. RESULTS: After the first night of NCPAP therapy, the Rrs decreased (sitting: 4.8+/-0.4 vs 4.3+/-0.4 cm H20/L/s, p < 0.05; lying: 6.5+/-0.4 vs 5.6+/-0.4 cm H20/L/s, p < 0.05) and the maximal voluntary ventilation increased in the morning (sitting: 101.6+/-5.8% vs 106.4+/-4.5%, p < 0.05; lying: 91.2+/-5.4% vs 97.9+/-4.7%, p < 0.05). The overnight difference in the SGrs showed a significant improvement after the initial treatment with NCPAP therapy (p < 0.05). However, the lung volume, flow volume loop, and closing volume in the morning did not change significantly after the therapy. An overnight decrease in the Rrs following NCPAP therapy is significantly correlated with the body mass index (sitting: r=0.54, p < 0.05; lying: r=0.61, p < 0.01). CONCLUSION: The improvements in Rrs without changes in spirometry may reflect improved upper airway patency after NCPAP therapy. The degree of obesity is suggested to be associated with the treatment effect on upper airway in patients with OSAS.     

Long-lasting sensitization to food during the first two years precedes allergic airway disease. The MAS Study Group, Germany

Measurement of eosinophil percentages and ECP concentration in induced sputum may be useful in the diagnosis and assessment of the variability of airway inflammation in bronchial asthma (BA). To evaluate the usefulness of sputum eosinophil counts and ECP concentrations in the diagnosis of BA, we measured these parameters in 68 patients with respiratory complaints. In addition, we followed-up 14 BA patients with variable airflow limitation for 45.4 +/- 10.4 days. The BA group (n = 41) showed a higher percentage of sputum eosinophilia (24.5 +/- 7.6 vs. 2.2 +/- 2.9%, p < 0.001) and a higher level of sputum ECP (198.2 vs. 90.6 micrograms/L, p < 0.05) than those in the nonasthmatic group (NBA, n = 27). The sensitivity and specificity of sputum eosinophilia (> or = 5%) for the diagnosis of BA were 85.4% and 92.6%, respectively, which were better than the sensitivity (68.3%) and specificity (55.5%) of the increased level of sputum ECP (> or = 100 micrograms/L). Patients with moderate-to-severe persistent BA had a higher percentage of sputum eosinophil (n = 23, 34.6 +/- 10.6%) than those of mild persistent BA (n = 18, 10.7 +/- 5.2%, p < 0.01), but we could not find significant difference in ECP levels between mild persistent and moderate-to-severe persistent asthma. The percentages of sputum eosinophilia showed a moderate correlation with ECP (r = 0.4358, p < 0.01) and with the peak expiratory flow rate (PFR, r = -0.4746, p < 0.01) but sputum ECP did not correlate with PFR. In 14 BA patients who were followed, there was a relationship between changes of PFR and the percentage of sputum eosinophil (r = -0.7238, p < 0.01), but the change of PFR did not correlate with the change of sputum ECP levels. These results suggest that the sputum eosinophil count and sputum ECP level could be helpful in the diagnosis of BA, but that sputum ECP is not satisfactory for the assessment of variability of airway eosinophilic inflammation during the initial anti-inflammatory management of BA.     

Inhaled furosemide prevents ultrasonically nebulized water bronchoconstriction in children with both atopic and nonatopic asthma

To determine whether inhaled furosemide can modify the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with both atopic and nonatopic asthma, a single-blind, randomized, placebo-controlled study was undertaken. The UNDW inhalation challenge was performed in 21 asthmatic children (atopic, 14; nonatopic, 7; mean +/- SEM age, 11.5 +/- 0.5 years), who had a fall in FEV1 of at least 20 percent after distilled water inhalation. On separate days, these subjects underwent UNDW challenge test after inhalation of furosemide (10 mg/body square meters) or placebo (saline solution). Inhaled furosemide exerted a protective effect against bronchoconstriction induced by UNDW in children with both atopic and nonatopic asthma (p < 0.01, p < 0.05, respectively). These results indicate that the protective action of furosemide against UNDW-induced bronchoconstriction may be independent of its direct inhibitory effect on airway mast cell activation.