Bronchial Eosinophilic Infiltration in Crohn's Disease in the Absence of Pulmonary Disease

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (1999), 29(5), 660-6

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine ... [more ▼]

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma. METHODS: Eighteen patients with Crohn's disease and 15 healthy controls matched for age, atopy and smoking habit, were studied. All the subjects underwent a bronchial methacholine challenge (1, 4 and 16 mg/mL) and a sputum induction by inhalation of hypertonic saline (NaCl 4.5%). The sputum samples were analysed for their cellular composition as well as for the levels of several mediators and proteins in the fluid phase, including eosinophil cationic protein (ECP), myeloperoxydase, albumin, alpha2-macroglobulin, interleukin-8 (IL-8), IgA and IL-8/immunoglobulin A complexes. RESULTS: When compared to control subjects, patients with Crohn's disease had significantly higher sputum eosinophil counts (14.5% [0-79.9%] vs 0.2% [0-2.3%]; P < 0. 001) and ECP levels (26.2 microg/L [4-124.2 microg/L] vs 9.8 microg/L [0-94.2 microg/L]; P < 0.05). However, patients with Crohn's disease had no sign of increased plasma exudation as reflected by sputum levels of albumin and alpha2-macroglobulin similar to those seen in control subjects. Furthermore the sputum levels of IL-8, IgA and IL-8/IgA complexes were not significantly different between the two groups. The magnitude of the fall in forced expiratory volume in 1 s after methacholine inhalation was significantly increased in Crohn's disease patients although it did not correlate with the extent of sputum eosinophilia or with the sputum ECP levels. CONCLUSIONS: Crohn's disease patients without any clinical respiratory involvement have airway eosinophilia without local increased plasma exudation. However, bronchial eosinophilia in Crohn's disease per se is not sufficient to induce clinically significant airway hyperresponsiveness, suggesting that other factors than bronchial eosinophilic infiltration are required for the clinical expression of an airway instability. [less ▲]

Theophylline Decreases Sputum Eosinophilia of Asthmatics

in International Archives of Allergy & Immunology (1999), 118(2-4, Feb-Apr), 343-4

Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.

in Clinical & Experimental Immunology (1998), 113(3), 401-406

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some ... [more ▼]

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals. [less ▲]

Les cysteinyl-leucotrienes: des mediateurs importants dans l'asthme

in Revue Médicale de Liège (1997), 52(9), 598-602

Correlation between Bronchoalveolar Lavage (Bal) Fluid Cell Lysate Histamine Content and Bal Fluid Eosinophil Count in Atopic and Nonatopic Asthmatics

in International Archives of Allergy & Immunology (1997), 112(3), 309-12

We have compared the bronchoalveolar lavage fluid (BAL) cellular composition and the BAL cell lysate histamine content (fluorometric assay) in 28 stable mild to moderate asthmatics (atopic n = 18 and ... [more ▼]

We have compared the bronchoalveolar lavage fluid (BAL) cellular composition and the BAL cell lysate histamine content (fluorometric assay) in 28 stable mild to moderate asthmatics (atopic n = 18 and intrinsic n = 10) and 11 control subjects. When compared to control subjects, the whole group of asthmatics had a higher proportion of BAL eosinophils (p < 0.01) and metachromatic cells (p < 0.05). The BAL cell lysate histamine was increased in atopic (p < 0.05) and intrinsic asthmatics (p < 0.05) in comparison with control subjects. In the whole group of asthmatics, the BAL cell lysate histamine content correlated with the percentage of BAL eosinophils (r = 0.58, p < 0.01). This relationship was significant in both atopic (r = 0.48, p < 0.05) and intrinsic (r = 0.70, p < 0.05) asthmatics. For the whole group of asthmatics, both the BAL cell lysate histamine and the percentage of BAL eosinophils inversely correlated with the percent predicted FEV1 (r = -0.42, p < 0.05; r = -0.51, p < 0.05). We conclude that an increased BAL cell lysate histamine content correlates with airway eosinophilic infiltration and lung function impairment in mild to moderate atopic and intrinsic asthmatics. This suggests that BAL mast cells play a key role in recruiting eosinophils in the airways of asthmatics irrespective of the presence of an atopic status. [less ▲]

Usefulness of Induced Sputum Analysis in Pulmonary Diseases

in Acta Clinica Belgica (1997), 52(2), 106-11

In this study, we analysed the cellular component of induced sputum in healthy control subjects (n = 30), asthmatics (n = 44), patients suffering from COPD (n = 15), pulmonary tuberculosis (PTB) (n = 14 ... [more ▼]

In this study, we analysed the cellular component of induced sputum in healthy control subjects (n = 30), asthmatics (n = 44), patients suffering from COPD (n = 15), pulmonary tuberculosis (PTB) (n = 14) and healthy steel workers (HSW) (n = 14). [less ▲]

Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine.

in European Respiratory Journal (1996), 9(7), 1414-20

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in ... [more ▼]

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p < 0.05), while it was 11 fold lower for methacholine (p < 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p < 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p < 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups. [less ▲]

Regulation of Histamine Release from Human Bronchoalveolar Lavage Mast Cells by Stem Cell Factor in Several Respiratory Diseases

in Allergy (1995), 50(4), 340-8

We investigated the effects of stem cell factor (SCF) on histamine release (HR) from human bronchoalveolar lavage (BAL) mast cells. BAL cells were recovered from lavage performed in patients undergoing ... [more ▼]

We investigated the effects of stem cell factor (SCF) on histamine release (HR) from human bronchoalveolar lavage (BAL) mast cells. BAL cells were recovered from lavage performed in patients undergoing clinical bronchoscopy. SCF (0.02-20 ng/ml), which is by itself a poor secretagogue (mean +/- SEM HR: 3.7 +/- 0.9%; n = 27), strongly enhanced HR induced by anti-IgE in a concentration-related manner. Significant potentiation began at 0.2 ng/ml (30 +/- 10%; p < 0.05; n = 12) and reached a plateau at 2 ng/ml (40 +/- 10%; P < 0.01 at 2 ng/ml and 45 +/- 10%; P < 0.01 at 20 ng/ml; n = 12). In contrast, SCF failed to enhance HR induced by calcium ionophore A23187. Among the BAL cell samples initially unresponsive to anti-IgE (55% of samples), 36% (10/28) were converted to responders if the cells were shortly preincubated with SCF. In 25% of samples (7/27), SCF (20 ng/ml) caused direct HR of 10 +/- 2.1%. The mast cells which released histamine when challenged with SCF also secreted higher levels of histamine in response to anti-IgE and calcium ionophore than those nonresponsive to SCF. While interleukin (IL)-3 and IL-5 (20 ng/ml) were unable to modulate immunologic HR, GM-CSF (20 ng/ml) produced significant potentiation (P < 0.05), which was, however, smaller than that observed with SCF.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Le BOOP: bronchiolitis obliterans and organising pneumonia, mythe ou réalité?

in Revue Médicale de Liège (1995), 50(3), 108-9

Increased frequency of bronchial hyperresponsiveness in patients with inflammatory bowel disease.

in Allergy (1995), 50(9), 729-33

Although bronchopulmonary manifestations are rare in inflammatory bowel disease (IBD), subclinical abnormalities have been described in up to 50% of cases. The pathophysiology of these abnormalities ... [more ▼]

Although bronchopulmonary manifestations are rare in inflammatory bowel disease (IBD), subclinical abnormalities have been described in up to 50% of cases. The pathophysiology of these abnormalities remains unknown. However, a latent inflammation of the bronchial mucosa secondary to the inflammation of the intestinal mucosa has been suggested. This subclinical inflammation may lead to increased bronchial responsiveness. We studied the bronchial responsiveness in 38 inflammatory bowel disease (IBD) patients, using the methacholine test. Bronchial hyperresponsiveness was defined by a PC20M < 16 mg/ml. Twenty-four healthy controls were also studied. There was no significant difference in baseline FEV1 between IBD patients and controls. However, there was a significantly greater fall in FEV1 in the IBD patients at the concentrations of methacholine tested. The frequency of bronchial hyperresponsiveness was significantly higher in the IBD population (45%) than in controls (17%; P < 0.03). Atopy, defined by skin test, was more common in IBD patients (42%) than in controls (21%). Even when only nonatopic subjects were considered, the frequency of bronchial hyperresponsiveness was significantly higher in IBD patients (41%) than in controls (5%; P < 0.02). Thus, subclinical bronchial hyperresponsiveness is common in IBD, and may be considered a further extraintestinal manifestation. [less ▲]