Gunnemar Stålenheim

Secretion of granule proteins from eosinophils and neutrophils is increased in asthma.

The activity of eosinophil and neutrophil granulocytes with respect to secretion of granule proteins was studied in 30 patients with asthma and with varying severity of their disease. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase was measured by means of specific radioimmunoassays. Eosinophils from patients with asthma released significantly more (p less than 0.001) ECP and EPX after 20 minutes of incubation than cells from control subjects without asthma. The release of myeloperoxidase from neutrophils was also somewhat higher (p less than 0.03). The serum concentrations of ECP and EPX were also significantly increased (p less than 0.001) in the group with asthma. No significant relationships were found between clinical variables and the secretory activity of either eosinophils or neutrophils. We conclude that eosinophils and, to some extent, neutrophils from subjects with asthma have an increased propensity to release their granule proteins, which we suggest is a consequence of priming of these cells.

Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season†

The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen-atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure.

Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjögren's syndrome

Background: Different mechanisms may underlie bronchial hyperresponsiveness (BHR) in different diseases. The aim of this study was to investigate the bronchial responsiveness profile produced by three different challenge tests, methacholine, a direct simulus, and two indirect stimuli, adenosine 5′‐monophosphate (AMP) and cold air, in subjects with asthma and patients with Sjögrens syndrome.

Study of the Th1/Th2 balance, including IL‐10 production,in cultures of peripheral blood mononuclear cells frombirch‐pollen‐allergic patients

Background: Excessive production of interleukin (IL)‐4, IL‐5, IL‐10, and IL‐13 is thought to be important in the development of allergy and asthma. The objective of this investigation was to study Th1/Th2‐like cytokine profiles in vitro in seven patients allergic to birch pollen and six nonallergic controls during the birch‐pollen season.

The acute effect of high dose corticosteroid treatment on serum osteocalcin

Osteocalcin is a vitamin K-dependent protein that is synthesized by osteoblasts and present in circulation. We measured serum osteocalcin concentrations in nine asthmatics before and during treatment with high IV dosages of glucocorticoids, betamethasone 0.65 mg/h. This treatment induced within 13 +/- 1.5 (SEM) hours a reduction of serum osteocalcin form 2.6 +/- 0.3 (SEM) to 1.2 +/- 0.3 microgram/L (P less than .001). During the following 24-hour period the osteocalcin levels further declined and reached a level about 30% of the pretreatment level. Continued treatment did not induce a further reduction of serum osteocalcin. A positive correlation was seen between the pretreatment osteocalcin concentration and the steady-state osteocalcin value during steroid therapy. The corticosteroids did not influence the serum calcium and phosphate concentrations but induced a minor, significant (P less than .001) decrease of serum alkaline phosphatase. After completion of steroid therapy, the osteocalcin values remained depressed for another 24 hours but had reached the pretreatment levels after another three days. Our data suggest osteocalcin as a sensitive marker of the corticosteroid induced depression of osteoblast activity.

A 3-year follow-up of asthmatic patients participating in a 10-week rehabilitation program with emphasis on physical training

OBJECTIVE To determine if asthmatic patients who had participated in a 10-week rehabilitation program with emphasis on physical training (1) continued with physical training, (2) maintained their improved cardiovascular condition and lung function, and (3) retained their good asthma control through the following 3 years. DESIGN A descriptive 3-year follow-up study. PATIENTS AND SETTING A convenience sample of 58 patients who had previously undergone a 10-week outpatient rehabilitation program were followed up 6 months and 1, 1.5, 2, and 3 years after the start of the program at a lung clinic in a university hospital. MAIN OUTCOME MEASURES A training log was kept by each patient to record frequency, intensity, and mode of training. Physical condition was evaluated with a submaximal 6-minute ergometry test and a 12-minute walking test, respiratory function with static and dynamic spirometry, and bronchial hyperreactivity with a metacholine provocation test. Asthma symptoms and asthma control were measured with a study-specific questionnaire. RESULTS Thirty-nine subjects (68%) exercised regularly during all 3 years. The cardiovascular condition and lung function values remained almost unchanged in all 58 patients. There was a significant decrease in number of emergency room visits the year after the 10-week rehabilitation program compared to the year before. It remained stable throughout the following 2 years. There was also a decrease in asthma symptoms in all patients, but the decrease was significant only in a subgroup of 26 patients, who exercised one or two times a week. CONCLUSIONS It is possible for asthmatic subjects to exercise at a moderate intensity level on a long-term basis without deleterious effects. Moreover, the high compliance rate might indicate that inactive asthmatic patients who are taught how to exercise choose to continue to be physically active.

Migratory responses of eosinophil and neutrophil granulocytes from patients with asthma

In the present study the migratory function of eosinophil and neutrophil granulocytes from patients with asthma were investigated. Fifty-seven patients with asthmatic disease of varying severity were included. Eosinophil and neutrophil chemotactic responses to 5% pooled normal human serum (NHS), 5% allergen-challenge serum, 2.5% zymosan-activated serum, N-formyl-methionyl-leucyl-phenylalanine (10 nmol/L), chemokinetic responses to albumin (2 gm/L) and 5% NHS, and the eosinophil and neutrophil chemotactic and chemokinetic activities of serum were investigated. Eosinophils from patients with asthma demonstrated significantly (p less than 0.02) increased chemotactic responses to allergen-challenge serum, zymosan-activated serum, and N-formyl-methionyl-leucyl-phenylalanine, compared with eosinophils from references. The chemokinetic responses to albumin and NHS were increased (p less than 0.01) by eosinophils from the patients who had blood eosinophilia (greater than 400 X 10(6)/L). Sera from the patients with asthma demonstrated raised eosinophil chemotactic activity (p less than 0.001) and raised eosinophil and neutrophil chemokinetic activity (p less than 0.001). The eosinophil chemokinetic activity of serum was correlated to the relative peak expiratory flow rate of the patients (r = -0.43; p less than 0.02). The increased migratory responses were specific for the eosinophils, since the migratory responses of their neutrophils were not altered compared with that of the references. These results suggest that the eosinophils from the patients with asthma had been exposed to a priming mechanism in vivo.

Intestinal reactivity in allergic and nonallergic patients: An approach to determine the complexity of the mucosal reaction

BACKGROUND To determine whether inflammatory markers and mediators were released in response to different intestinal antigens, studies were performed in atopic patients allergic to birch, patients allergic to psyllium powder (ispaghula), and patients intolerant to milk. METHODS Allergy to birch and psyllium powder was documented by the presence of circulating IgE antibodies and positive skin tests. Patients intolerant to milk had negative outcomes of radioallergosorbent tests and skin tests but positive results of double-blind, placebo-controlled tests. Challenge of the intestine with different antigens was achieved by perfusion of a jejunal segment occluded between balloons. Basal and antigen-activated release of mast cell/basophil and eosinophil products and of substances emanating from the plasma and interstitial fluid was compared in perfusate fluid from patients (n = 8) and matched healthy controls (n = 8). RESULTS Perfusate levels of albumin and hyaluronan (previous name hyaluronic acid) were increased threefold to fivefold by antigen in all patients, but not in controls. Eosinophilic cationic protein increased in patients but also in ispaghula controls. Histamine was released in response to milk, but not in patients allergic to birch or ispaghula. Prostaglandin E2 increased in milk- and birch-sensitive patients. In response to ispaghula, however, it was released in both patients and controls. CONCLUSIONS We conclude that subclinical intestinal challenge with antigen induces an increase in the appearance rate of albumin and hyaluronan in the intestinal lumen both in atopic patients (with target organs such as the lungs or nose and eyes) and in patients with intestinal intolerance to milk. These changes in permeation are similar to those reported from other organs such as the lung. They may reflect a common response in early phase I reactions that are either IgE-mediated or occur in response to food antigens without any obvious involvement of an IgE-mediated mechanism. Subclinical provocation with intestinal antigens should prove useful for further elucidation of mechanisms underlying intestinal mucosal reactions to exogenous stimuli.

A (G→C) transversion in the 3′ UTR of the human ECP (eosinophil cationic protein) gene correlates to the cellular content of ECP

Eosinophil cationic protein (ECP) is a cytotoxic protein produced by and secreted from human eosinophil granulocytes. ECP may be involved in the injury of epithelial cells in allergic diseases such as asthma. The objectives were to determine the prevalence of the ECP gene polymorphism 562(G>C) in apparently healthy subjects and subjects with allergy and relate the prevalence to clinical disease and to serum and cellular levels of ECP. The 562(G>C) ECP gene polymorphism was determined by gene sequencing of the ECP gene from DNA prepared from 163 apparently healthy subjects and 151 subjects with allergic and nonallergic asthma or other diseases. ECP was measured by a sensitive radioimmunoassay. A polymorphism was detected at position 562, which mapped to the 3′ untranslated region (UTR) of the gene encoding the ECP (RNase 3). Sixty‐nine percent of the population had the 562GG genotype and 4%, the 562CC genotype. The cellular content of ECP in peripheral blood eosinophil granulocytes was significantly lower in cells from subjects with the 562GC (4.6±1.5 μg/106 eosinophils) and 562CC (3.2±0.7 μg/106 eosinophils) genotypes as compared with those with the 562GG genotype (6.0±1.9 μg/106 eosinophils; P<0.001). A close link was found to the 434(G>C) ECP gene polymorphism. Associations between the 562(G>C) polymorphism or haplotypes of the two polymorphisms to allergy were not found. The 562(G>C) polymorphism in the 3′‐end of the UTR of the ECP gene may determine the ECP content in human eosinophils, but unlike the 434(G>C) polymorphism, the 562(G>C) polymorphism is not related to allergy

High-intensity physical training in adults with asthma. A comparison between training on land and in water.

The purpose of this study was to determine whether inactive asthmatic patients could perform high-intensity physical training equally well on land as in water, and to compare the effects of these training forms. Thirty-two adults with asthma, randomized into two groups, underwent a 10-week supervised rehabilitation program with emphasis on physical training. All patients, irrespective of training form, were able to exercise to maximal intensity (80-90% of estimated maximal heart rate). No asthmatic attacks occurred in connection with the training sessions. Respiratory variables remained almost unchanged in both groups. The asthma symptoms declined during the rehabilitation period, and the subjects needed less acute asthma care after the rehabilitation. The cardiovascular condition improved significantly and similarly in the two groups. Ten patients, 5 in each group, had exercise-induced asthma at the start of the rehabilitation. Only 3 patients, 2 from the water group and 1 from the land group, had exercise-induced asthma after 10 weeks. We conclude that indoor training, either on land or in water, is beneficial. The effects of these two training forms are almost equivalent.