Assessment of magnesium status in patients with bronchial asthma.

To elucidate the contribution of magnesium to bronchial hyperreactivity in patients with stable bronchial asthma, magnesium concentrations in serum (S-Mg), erythrocytes (R-Mg), and lymphocytes (L-Mg) were measured in 25 patients with bronchial asthma (BA group) and 9 age-matched healthy subjects (control group). A parenteral magnesium loading test, a continuous low-dose magnesium infusion of 0.2 mEq/kg over 4 hr, was performed in 10 of 25 asthmatic patients and in the control group. R-Mg was significantly lower in the BA group than in the control group (4.96 +/- 0.47, 6.13 +/- 0.62 mEq/L, p < 0.001, respectively), although S-Mg (2.4 +/- 0.1, 2.4 +/- 0.2 mg/dL) and L-Mg (1.28 +/- 0.26, 1.15 +/- 0.13 microg/mg/protein) were not significantly different between the two groups. Magnesium deficiency in total body stores was revealed in 40% of patients (4/10 patients) and 11% of control subjects (1/9 subjects) by parenteral magnesium loading test. The ratio of magnesium retention to urinary excretion through the parenteral magnesium loading test showed a significant inverse correlation with R-Mg (r = -0.78, p < 0.01). Bronchial reactivity to inhaled methacholine had a significant inverse correlation with R-Mg (r = -0.42, p < 0.05). We conclude that 40% of asthmatic patients demonstrated magnesium deficiency, and that the low magnesium concentration in erythrocytes reflects decreased magnesium stores in patients with bronchial asthma.     

A study on the relationship between histamine receptors and bronchial hyperresponsiveness in asthma]

We measured the bronchial response to histamine in 26 allergic asthmatics and 17 healthy subjects before and after the bronchial pretreatment with selective H2-receptor antagonist ranitidine. We also investigated the results of the new H1-receptor antagonist terfenadine on the prevention and treatment of asthma. Selective H1-receptor stimulation with histamine (pretreated with 18.5mg ranitidine) failed to enhance the effect of histamine in asthma group (P greater than 0.05), whereas it enhanced the histamine response obviously in healthy group (P less than 0.001). We conclude that: 1. BHR to histamine in allergic asthma is related to a functional depression of H2 receptors in airways; 2. terfenadine is useful in the prevention and treatment of asthma.     

Effect of cold air exposure and exercise on nonspecific bronchial reactivity

Exercise and eucapnic hyperventilation with cold air can produce bronchoconstriction in asthmatic subjects, but their enhancement of nonspecific bronchial reactivity remains unclear. We studied the effect of submaximal exercise and cold air exposure on bronchial reactivity to methacholine in a normal control group (n = 10) and in subjects with bronchial asthma (n = 17). Bronchial provocation testing was performed to determine the provoking dose (PD35) of methacholine that caused a 35 percent decrease in specific airway conductance (Gaw/VL) in the two groups. Each subject was studied on three different occasions to determine the PD35 to methacholine on a control day, after ten minutes of submaximal exercise, and after a 30-minute exposure to cold air. Methacholine challenge was performed after the Gaw/VL had returned to the baseline values. In the normal group, neither cold air exposure nor exercise challenge had any significant effect on baseline Gaw/VL, whereas in the asthmatic group, both stimuli caused 20 percent and 15 percent decreases in Gaw/VL, respectively (p less than .05). Mean +/- SD control PD35 was 6.1 +/- 11.6 breath units in the asthmatic group, which decreased to 2.2 +/- 2.8 after exercise and 3.0 +/- 5.0 breath units after cold air exposure (p less than .05). In the normal group, control PD35 was 73 +/- 32 breath units, which was not different from PD35 values of 64 +/- 75 and 52 +/- 64 breath units after exercise and cold air exposure, respectively (p = NS). These data suggest that submaximal exercise and cold air exposure enhance nonspecific bronchial reactivity in asthmatic but not in normal subjects.     

A study of the relationship between serum group I pepsinogen levels and gastric acid secretion.

Serum group I pepsinogen (PG I) levels, basal acid output, and peak acid output (PAO) have been determined in 120 patients, 54 with duodenal ulcer, 14 with prepyloric ulcer, 12 with gastric ulcer, and 40 without ulcer. The correlation between serum PG I and PAO was statistically significant (r = 0.736, P less than 0.001) up to a serum PG I level of 250 ng per ml. Serum PG I levels above 250 ng per ml were associated with a plateau in the PAO. Each of 8 patients with a serum PG I of less than 40 ng per ml had a PAO of less than 10 mEq per hr. Of 34 patients with a serum PG I over 200 ng per ml, 29 (85.3%) had a PAO of greater than 40 mEq per hr and all had a PAO above 34 mEq per hr. Of 51 patients with a serum PG I between 60 and 150 ng per ml, 47 (92.2%) had a PAO of between 10 and 40 mEq per hr. The results indicate that a significant relationship exists between the concentration of PG I in serum and the acid secretory capacity of the gastric mucosa.     

Human basophil releasability. VI. Changes in basophil releasability in patients with allergic rhinitis or bronchial asthma.

We evaluated basophil releasability in two groups of allergic patients with positive skin tests to Dermatophagoides pteronyssinus major allergen (Der p l) (29 adults with bronchial asthma and 17 with allergic rhinitis) and in 31 age-matched normal donors. Both basophil reactivity (maximal percent histamine release) and basophil sensitivity (the concentration that causes 50% of maximal percent histamine release: HC50) to Der p l in patients with asthma were similar to those in patients with allergic rhinitis. On the contrary, basophil reactivity to anti-IgE was significantly higher in patients with asthma (58.0 +/- 3.6%) than in patients with allergic rhinitis (46.3 +/- 5.2%; p less than 0.05). Both groups of patients showed an increased releasability compared to control subjects (27.3 +/- 4.6%; p less than 0.001), whereas there were no significant differences in basophil sensitivity to anti-IgE among the three groups of donors. Differences were also found with respect to basophil reactivity and sensitivity to f-met peptide, whereas no differences appeared when basophils from the three groups of donors were challenged with the Ca2+ ionophore A23187. There was a significant correlation between basophil reactivity and sensitivity to Der p l and to anti-IgE in both asthmatic and allergic rhinitis patients. A significant correlation was found between basophil reactivity and sensitivity to anti-IgE and serum IgE level only in patients with bronchial asthma, whereas no correlations were found in patients with allergic rhinitis. There was no correlation between in vivo mast cell releasability and in vitro basophil releasability in response to Der p l in either group of allergic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum group I pepsinogen levels and their relation to gastric acid secretion in patients with and without recurrent ulcer.

Serum group I pepsinogen (PG I) levels have been determined by radioimmunoassay in 15 patients without, recurrent ulcer after vagotomy and either a gastric resection or a drainage procedure. The mean (+/-SE) levels were 151.8 +/- 16.9 ng per ml in the patients with recurrent ulcer and 79.7 +/- 9.8 ng per ml in those without recurrence (P less than 0.001). A recurrent ulcer was present in 6 of 7 patients with an elevated serum PGI (greater than 175 ng per ml) but not in any of 10 patients with a low serum PGI (less than 50 ng per ml). The correlation between serum PG I and peak acid output (PAO) was statistically significant in patients with recurrent ulcer (pi=0.815, P less than 0.001) and in those without recurrence (r= 0.540, P less than 0.025). In patients with recurrent ulcer, a serum PG I level within the normal range (50 to 175 ng per ml) was uniformly associated with a PAO of more than 10 mEq per hr. In contrast, of 10 patients without recurrent ulcer and a normal serum PG I, eight had a PAO of less than 10 mEq per hr. The reason for the discordant results in the two groups of patients is not certain.     

Mucociliary transport in allergic patients with antigen-induced bronchospasm.

Tracheal mucous velocity (TMV) and respiratory mechanics were measured in asymptomatic asthmatic patients with ragweed hypersensitivity before and after inhalation of specific antigen, and with or without cromolyn sodium pretreatment. TMV was measured radiographically, and the airway response to bronchial provocation was monitored by measurements of forced expiratory volume in one sec and specific airway conductance. TMV was significantly less (6.3 +/- 2.3 mm per min, mean +/- SD) in the 6 asymptomatic asthmatic patients than in 7 normal subjects (11.6 +/- 3.6 mm per min, mean +/- SD). In the asthmatic patients, mean TMV diminished to 72 per cent of baseline immediately after bronchial provocation when specific airway conductance was decreased to 65 per cent of baseline or less, with a further decrease in TMV to 47 per cent of baseline after one hour, at which time respiratory mechanics had returned to baseline values. Pretreatment with cromolyn sodium prevented the decrease in TMV after bronchial provocation. We concluded that in asymptomatic patients with allergic asthma, (1) baseline TMV is impaired, (2) inhalation of specific antigen causes a marked decrease in TMV independent of the degree of bronchospasm, and (3) the decrease in TMV may be related to the release of chemical mediators.     

Comparison between bronchial and alveolar samples of bronchoalveolar lavage fluid in asthma.

BACKGROUND: Cell content of BALF may vary according to the segment of the lung washed. It was proposed to separate BALF into several aliquots, the first sample being more related to bronchi. The present study compared bronchial and alveolar samples by fractionating aliquots of BALF in normal and asthmatic subjects. METHODS: One hundred asthmatic subjects (mean +/- SEM: 37 +/- 1.5 yr in age) were compared with 31 normal subjects (mean +/- SEM: 32 +/- 2.2 yr in age). None of the subjects was a smoker and none was taking drugs that might interfere with the results. The severity of asthma was defined by the clinical score of Aas examining the chronic severity of asthma and ranging from 1 to 5 (range: 1 to 4; mean +/- SEM: 2.2 +/- 0.1) and FEV1 (range: 45 to 130 percent; mean +/- SEM: 82 +/- 1.8 percent of predicted values). Bronchoscopy was done in a standardized manner. A first aliquot of 50 ml of saline each were instilled and the BALF recovered was pooled (alveolar sample). After centrifugation, total and differential cell counts (May Grünwald-Giemsa) were carried out on bronchial and alveolar samples. RESULTS: The alveolar sample contained significantly more cells per milliliter of BALF than the bronchial sample in normal (p less than 0.0077, Wilcoxon test) and in asthmatic subjects (p = 0.0001, Wilcoxon test). Both in normal and asthmatic subjects, bronchial samples contained significantly more neutrophils and epithelial cells and fewer macrophages and lymphocytes than alveolar samples. In asthmatic subjects, the bronchial sample contained a significantly greater percentage of eosinophils than the alveolar sample. Eosinophils were significantly increased in asthmatic subjects for both the bronchial and alveolar samples. Bronchial and alveolar eosinophilia both were correlated with the Aas score (r = 0.25, p = 0.024 and r = 0.38, p = 0.0006, respectively, by Spearman Rank test). CONCLUSIONS: This study shows in a large number of subjects that the cell content of bronchial and more distal segments of the lung is not comparable, indicating that studies should not give pooled data in asthmatic subjects. Moreover, it confirms the presence of BALF eosinophilia in asthmatic subjects.     

Serum levels of eosinophil cationic protein and eosinophils in asthmatic children during a course of prednisolone therapy

Eosinophils play an important role in the inflammatory events of allergic asthma. Serum eosinophil cationic protein (ECP) is a marker of disease activity and of treatment efficacy in bronchial asthma. To understand the role of ECP concentrations in disease activity of acute asthma, we determined changes in serum concentrations of ECP elaborated by activated eosinophil before and after prednisolone therapy. Circulating levels of ECP in 15 normal control subjects, and in sera of 20 asthmatic children who were allergic to house dust mites, were measured during an acute exacerbation and when the children were in stable condition, using commercially available assay kits. The mean concentrations of serum ECP were significantly higher during an acute asthma exacerbation than when the children were stable (26.41 +/- 21.66 microg/L vs 15.74 +/- 11.36 microg/L P < 0.01) or when compared to control subjects (7.50 +/- 1.42 microg/L; P < 0.001). The mean eosinophil counts (EC) during acute asthma attacks (575 +/- 286/mm3) and when stable (467 +/- 204/mm3) were higher than in the control group (181 +/- 164/mm3). The differences were statistically significant among the three groups (P < 0.05). A significant correlation was found between serum levels of ECP and EC (r = 0.788, P = 0.001) in asthmatic children; there were also significant correlations between ECP and EC in nonallergic normal control subjects (r = 0.662; P = 0.007). In conclusion, this study provides further evidence that changes in serum ECP may serve as an objective indicator for clinical activity and results of treatment in allergic asthmatics.     

Secretory function of the stomach of Japanese with endoscopically normal gastric mucosa.

Using gastrin-like AOC-tetrapeptide the secretory function of the stomach of Japanese with endoscopically normal gastric mucosa was examined in a multicenter clinical study. Mean one hour secretion volume, mean maximal acidity, and mean maximal acid output were found to be 129.3 +/- 60.0 ml/hr, 103.7 +/- 32.4 mEq/l, and 9.2 +/- 6.9 mEq/hr respectively. Results were analysed according to sex or age by analysis of variance and compared further with the corresponding data reported in the literature.     

Unimodal distribution of bronchial hyperresponsiveness to methacholine in asthmatic patients.

Distribution of bronchial hyperresponsiveness to methacholine was assessed in 791 consecutive patients who were referred to the outpatient clinic of the pulmonary department due to asthmatic or persistent lower airway symptoms. Bronchial asthma was diagnosed in 319 patients. Clinical sensitivity of methacholine challenge for the disease was 89 percent and specificity, 76 percent. The degree of bronchial hyperresponsiveness in the entire group of asthmatic patients was unimodally log normal distributed. Of the 82 patients with allergic rhinitis without concurrent asthma, 27 percent had bronchial hyperresponsiveness, but of a markedly lesser degree than in the hyperresponsive asthmatic patients. In 49 patients with chronic bronchitis, 22 percent had hyperresponsiveness. The present data indicate that the degree of bronchial hyperresponsiveness in asthmatic patients is unimodally distributed, supporting the view that both genetic and environmental factors have an impact upon its development. Although the degree of bronchial hyperresponsiveness in asthma is more pronounced than in allergic rhinitis or in chronic bronchitis, a marked overlap exists.     

Beta-adrenergic receptors of lymphocytes in children with allergic respiratory diseases

The beta-adrenergic receptor binding sites on peripheral lymphocytes in children with bronchial asthma (n = 16) and seasonal allergic rhinitis (n = 8) were examined in comparison with normal controls (n = 18) by means of 124I-cyanopindolol. The number of beta-adrenergic receptors was significantly lower in the asthmatic group (858 +/- 460/lymphocyte) than in the controls (1564 +/- 983/lymphocyte). The value (1891 +/- 1502/lymphocyte in children with allergic rhinitis was slightly higher than that in healthy controls. Of the 24 patients suffering from allergic diseases of the lower or upper airways, the bronchial histamine provocation test was performed in 21; 16 gave positive results, while 5 were negative. No difference in beta-adrenergic receptor count was found between the histamine-positive and negative patients. Neither was there any correlation between the number of beta-adrenergic receptors and the high (16/24) and low (8/24) serum IgE concentrations found in allergic patients. The significant decrease in beta-adrenergic receptor count in asthmatic children lends support to Szentiványi's concept. Further qualitative and quantitative analysis of lymphocyte beta-adrenergic receptors may provide an individual approach to the treatment of bronchial asthma with beta-sympathomimetic drugs.     

Evaluation of serum interleukin-8 as a marker of disease activity in acute asthma in children.

Cytokine-mediated interactions among the inflammatory cells may play a role in the pathogenesis of bronchial asthma. Interleukin-8 (IL-8) is a major cytokine in the recruitment of neutrophils to the area of inflammation. Serum IL-8 is a marker of disease activity and treatment efficacy in bronchial asthma. To understand the role of IL-8 in disease activity in acute asthma, changes in serum concentrations of IL-8 elaborated by activated eosinophil before and after prednisolone therapy with clinical improvement were determined in the present study. Circulating levels of IL-8 in 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in stable condition were determined by using commercially available assay kits. The mean concentration of serum IL-8 was statistically significantly higher in asthmatic children with acute exacerbation (63.62 +/- 11.41 pg/mL) and in stable asthmatics (64.22 +/- 10.31 pg/mL) compared to the control group subjects (50.40 +/- 30.70 pg/mL; p < 0.01). However, the difference was not statistically significant between the acute exacerbation and stable asthmatics groups (p > 0.05). Serum IL-8 is a poor indicator of disease activity in acute asthma; therefore, monitoring by serum IL-8 concentration is of limited value. The clinical value of serum IL-8 as a marker of disease activity remains to be established.     

The association of gastroesophageal reflux with bronchial asthma. Can asthma also trigger reflux?

BACKGROUND/AIMS: The frequency of gastroesophageal reflux (GER) among asthmatic patients was found to range from 34% to 89% at different locations. The aims of this study have been to determine the frequency of GER in patients with asthma in the Saudi environment, to ascertain the main mechanism whereby GER triggers asthma, and to seek any evidence whether asthma can also trigger GER. METHODOLOGY: Fifty asthmatic patients were consecutively recruited as they reported to King Fahd Hospital of the University (KFHU), Al-Khobar, Saudi Arabia, in the period from February 2000 to February 2001; their mean age +/- SD was 38.0 +/- 9.8 years. Twenty-two subjects without asthma or GER served as controls; their mean age +/- SD was 29.4 +/- 8.6. Both groups were subjected to a questionnaire, esophageal manometry, dual probe ambulatory 24-hour pH monitoring, and pulmonary function tests. RESULTS: Among the asthmatic group 22 patients (44%) had GER. Accordingly, the asthmatic patients were divided into two groups: asthmatic with GER (n=22), and asthmatic without GER (n=28). Hoarseness of voice and nocturnal symptoms were found to be significant predictors for the presence of GER in asthmatics. Manometry revealed that asthmatic patients with GER had higher gastric pressure (11.4 +/- 4.0 mmHg vs. 8.4 +/- 2.8 mmHg; p=0.006) and lower resting pressure at the lower esophageal sphincter (LES) (21.2 +/- 8.7 mmHg vs. 28.2 +/- 9.3 mmHg; p=0.013) when compared with controls, both factors favoring the occurrence of reflux. With regard to pH data, acid reflux occurred both at the distal and proximal esophagus but the percent total acid exposure time was about 7 times longer at the distal than at the proximal esophagus (5.80 vs. 0.9). In addition, gastric pressure was positively and significantly correlated with distal esophageal acid exposure time and the DeMeester score, negatively correlated with spirometric parameters in asthmatic patients, as well as found to be a significant predictor of the severity of asthma (p=0.006). CONCLUSIONS: Forty-four percent of the sample of asthmatic patients reporting to KFHU had GER. Since distal esophageal total acid exposure time was nearly 7 times longer than at the proximal esophagus, the main mechanism for GER triggering asthma is the vagally mediated reflex initiated by acid in the distal esophagus. In addition, the positive correlation of increased gastric pressure with the distal esophageal acid exposure time and the DeMeester score, its negative correlation with spirometric parameters and being a significant predictor of asthma severity suggest that severe asthma may trigger or aggravate GER.     

Comparison of the effects of histamine H1- and H2-receptor agonists on large and small airways in normal and asthmatic subjects

It is accepted that histamine H1-receptors are present on human bronchial smooth muscle and that they mediate bronchoconstriction. However, the role of the histamine H2-receptor in the airways of man is less certain. In ten non-asthmatic and five asthmatic subjects we have compared the effects of inhalation of a specific H1-receptor agonist, betahistine, a specific H2-receptor agonist, impromidine and the combined H1- and H2-receptor agonist, histamine, on specific airways conductance and measurements from partial expiratory flow-volume curves. Both histamine and betahistine induced reproducible dose-dependent bronchoconstriction in all subjects, as assessed by all measurements made. Impromidine had no effect on measurements of airways function in either group of subjects. These results confirm the presence of bronchoconstricting H1-receptors, and the absence of significant numbers of H2-receptors on human bronchial smooth muscle. There is no difference in the distribution of these receptors in normal and asthmatic subjects.     

Peripheral Inflammation in Patients with Asthmatic Symptoms but Normal Lung Function

Some patients with asthmatic symptoms and eosinophilic airway inflammation have normal lung function and thus do not meet the current diagnostic criteria of asthma. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to assess alveolar and bronchial NO output and inflammation. We tested whether alveolar or bronchial NO output is increased in subjects having asthmatic symptoms but normal lung function. Exhaled NO concentration was measured at three exhalation flow rates (100, 175, and 370 mL/s) to assess alveolar NO concentration and bronchial NO flux in 23 patients with asthmatic symptoms but normal lung function (“asthmatic symptoms group”), 40 patients with asthma, and 40 healthy control subjects. The asthmatic symptoms group had increased bronchial NO flux (1.7 ± 0.3 nL/s, p = 0.016) and alveolar NO concentration (1.8 ± 0.2 parts per billiant (ppb), p = 0.010) compared with healthy controls (0.7 ± 0.1 nL/s and 1.0 ± 0.1 ppb, respectively). Patients with asthma had even higher bronchial NO flux (2.5 ± 0.3 nL/s, p = 0.024) but normal alveolar NO concentration (1.1 ± 0.2 ppb, p = 0.664). In asthmatic symptoms group, alveolar NO concentration correlated positively with blood eosinophil count and negatively with small airway function (FEF_50% and FEF_75%). In conclusion, patients with asthmatic symptoms but normal lung function have increased alveolar NO concentration and mildly elevated bronchial NO flux suggesting a more peripheral inflammation than in patients with asthma.     

A study on the functional condition of airway muscarinic M2-receptors in asthma]

We investigated the hypothesis that airway M2-receptor selectively pretreated with aerosolized pilocarpine would modify the bronchoconstrictor response to histamine, which is, in part, vagally mediated. On two different days, the following two histamine inhalation challenges were performed in 12 normal individuals and 13 stable asthmatics: histamine alone or pilocarpine-histamine. In normal subjects, prior M2-receptor stimulation with pilocarpine suppressed the subsequent bronchial response to histamine. In asthmatic patients, however, prior pilocarpine exposure failed to modify the bronchial response to histamine. The results suggest that prior M2-receptor stimulation has a protective effect on histamine induced bronchoconstriction in normal subjects and the absence of this inhibitory effect in asthmatic patients may represent the existence of functional depression of M2-receptors in asthmatic airways.     

Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender

BACKGROUND: In Japan, where the incidence of gastric cancer is high, Helicobacter pylori infection could affect gastric acid secretion differently from that in Western countries. The aim of this study was to investigate the relationship between H. pylori infection, acid secretion, aging, and gender in normal Japanese subjects. METHODS: The study comprised 193 Japanese subjects who had undergone routine endoscopy. Gastrin-stimulated acid output was performed during the routine endoscopic examination using the endoscopic method of gastric acid secretory testing (EGT: endoscopic gastrin test), which has been reported previously. H. pylori status was determined by histology, rapid urease test, and serology. RESULTS: Mean EGT values were 3.9 +/- 1.5 mEq/10 min in H. pylori-negative men, 1.6 +/- 2.5 in H. pylori-positive men, 2.2 +/- 0.9 in H. pylori-negative women, and 1.5 +/- 1.2 in H. pylori-positive women. Although acid secretion was lower in H. pylori-positive subjects compared with H. pylori-negative subjects in both men and women, the decrease was more marked in men with H. pylori infection. Multiple linear regression analysis showed that aging is positively associated with gastric acid secretion in the H. pylori-negative subjects, whereas a negative association was found between them in the H. pylori-positive subjects. CONCLUSIONS: In Japanese subjects, aging affects gastric acid secretion differently depending on the status of H. pylori infection. H. pylori infection showed a stronger inhibitory effect on the acid secretion in men than in women. This gender-related difference in the susceptibility of acid secretion to H. pylori infection may explain the higher rates of gastric cancer in men in Japan.     

Assessment of bronchial wall thickening on posteroanterior chest radiographs in acute asthma.

A central bronchus that is readily visible end-on in approximately 50% of normal frontal chest radiographs is the bronchus to the anterior segment of either upper lobe. Bronchial wall thickening, or "cuffing," is considered to be a radiographic sign of an asthmatic exacerbation and is cited as a useful sign in a number of leading textbooks; however, to the authors' knowledge, no prior chest radiographic study has quantitatively assessed this specific sign in a population of asthmatics suffering an acute exacerbation. Posterior chest radiographs were reviewed retrospectively for 51 nonasthmatic, nonsmoking control subjects and for 45 adult asthmatic subjects during an acute exacerbation of moderate to severe asthma. Readers were blinded as to whether the radiograph was from an asthmatic or control subject. If visible end-on, the bronchus to the anterior segment of either upper lobe was assessed by measuring the diameter of the lumen and the thickness of the bronchial wall. At least one clearly defined bronchus to the anterior segment of an upper lobe was visible end-on in 22 patients (43%) in the control group and in 21 patients (47%) in the asthma group (p = NS). Mean wall thickness was 0.7 +/- 0.1 mm in the control group and 0.8 +/- 0.1 mm in the asthma group (p = 0.04). Lumen/wall thickness was 3.1 +/- 0.2 (SEM) in the control group and 2.5 +/- 0.2 in the asthma group (p = 0.055). The presence of bronchial wall thickness does not reliably distinguish radiographs of acutely asthmatic from normal individuals.     

Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study

To determine the long-term efficacy, safety, and toxicity of omeprazole, we studied 40 patients with Zollinger-Ellison syndrome given omeprazole for 6-51 mo (median 29). The mean daily dose of omeprazole required to control gastric acid secretion was 82 +/- 31 mg. Thirty-one patients required omeprazole once per day. In 9 patients acid output was not controlled by 120 mg once per day, but was controlled by 60 mg every 12 h. The daily dose of omeprazole correlated with the previous dose of histamine H2-receptor antagonist (r = 0.89, p less than 0.001), basal acid output (r = 0.43, p less than 0.01), and maximal acid output (r = 0.39, p less than 0.02) but not with serum concentration of gastrin (r = -0.32). Increases in the dose of omeprazole were required in 9 patients. Twenty-nine patients had mild peptic symptoms with acid outputs less than 10 mEq/h while taking histamine H2-receptor antagonists. Symptoms resolved completely in 23 patients and partially in 3 when taking omeprazole. Omeprazole prevented mucosal disease in all patients including 17 in whom histamine H2-receptor antagonists had produced only partial resolution despite acid output being less than 10 mEq/h and in those with symptoms during omeprazole therapy. Omeprazole therapy was not associated with any significant side effects, nor with any evidence of hematologic or biochemical toxicity. Serum concentrations of gastrin did not change significantly during therapy. In 6 patients treated with omeprazole for 1 yr there was no change in basal or maximal acid output. In all patients, gastric morphology and histopathology demonstrated no evidence of gastric carcinoid formation. These results demonstrate that with long-term treatment of up to 4 yr, omeprazole is safe, with no evidence of hematologic, biochemical, or gastric toxicity. Furthermore, omeprazole remained effective, with only 23% of patients requiring an increase in dose, and continued to control symptoms in patients who had not been entirely symptom-free despite high doses of histamine H2-receptor antagonists. Omeprazole is now the drug of choice in patients with Zollinger-Ellison syndrome.