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Biomedical subjects

Frédéric de Blay

Publications and source records attributed to Frédéric de Blay.

9 recordsLinked to original sources

Marked stem cell factor expression in the airways of lung transplant recipients.

BACKGROUND: Airways repair is critical to lung function following transplantation. We hypothesised that the stem cell factor (SCF) could play a role in this setting. METHODS: We studied 9 lung transplant recipients (LTx recipients) during their first year postgraft, and evaluated SCF mRNA expression in bronchial biopsy specimens using on-line fluorescent PCR and SCF protein levels in bronchoalveolar lavage (BAL) and serum using ELISA. The expression of SCF receptor Kit was assessed using immunostaining of paraffin-embedded bronchial sections. RESULTS: SCF mRNA was highly expressed during the early postgraft period [Month (M)1-M3] (300% increase vs controls: 356 vs 1.2 pg SCF/microg GAPDH cDNA, p < 0.001) and decreased thereafter (M4-M12: 187 pg/microg), although remaining at all times 10-100 times higher than in controls. While SCF protein levels in BAL were similar in LTx recipients and in controls, the SCF serum levels were at all times higher in LTx recipients than in controls (p < 0.05), with no relationship between these levels and the acute complications of the graft. Finally, Kit was strongly expressed by the mast cells as well as by the bronchial epithelium of LTx recipients. CONCLUSION: SCF and Kit are expressed in bronchial biopsies from lung transplant recipients irrespective of the clinical status of the graft. A role for these factors in tissue repair following lung transplantation is hypothesised.

Acute Disease↗

Exposure to endotoxins during sensitization prevents further endotoxin-induced exacerbation of airway inflammation in a mouse model of allergic asthma.

BACKGROUND: We have shown previously that lipopolysaccharides (LPS) inhibited airway inflammation in allergen-sensitized and challenged mice when administered during sensitization, while exacerbating the inflammation when given upon challenge. We have here investigated the effect of LPS administered during both sensitization and challenge on airway inflammation, as well as on the profile of the T-helper (Th) response to allergen. METHODS: Mice were sensitized and challenged with ovalbumin (OVA), in the presence or absence of effective doses of LPS, namely 1 mug during sensitization and 1 ng during challenge. Inflammation was assessed by measuring cell counts and cytokine levels in bronchoalveolar lavage fluid (BALF). The profile of the Th response was determined by quantifying OVA-specific IgE and IgG2a in serum and Th1/Th2 cytokines in the culture medium of splenocytes and in BALF. RESULTS: Allergen-induced airway eosinophilia was increased in mice exposed to LPS during challenge only when compared with controls, whereas it was similarly reduced in animals exposed during sensitization only and during both sensitization and challenge. Mice exposed to LPS during sensitization only or during both sensitization and challenge also displayed a decrease in IgE and an increase in IgG2a, suggesting a switch in the immune response toward the Th1 profile. This was confirmed by quantification of Th1/Th2 cytokines in culture medium of splenocytes and in BALF. CONCLUSIONS: Our data demonstrate that exposure to endotoxins during sensitization prevents allergen-induced airway inflammation, as well as its exacerbation triggered by further exposure to endotoxins during challenge, while switching the immune response to allergen from a Th2 to a Th1 profile.

Animals↗

[The role of the environment in asthma: hypotheses and contradictions].

Three hypotheses are described to explain the relation between allergens and environmental co-factors and the onset of atopy: the hygiene hypothesis, the allergenic hypothesis, and the high exposure tolerance inducing a Th2 derived response with blocking IgG4 synthesis. None of these hypotheses have been confirmed. It seems thus difficult to give recommendations for primary prevention of allergic diseases until results of prospective studies allow to consider a more precise behaviour. In contrast, subjects sensitized and exposed to allergens present an increased risk to develop asthma or non specific bronchial hyperreactivity. Therefore, secondary prevention appears as an essential method for treatment of allergic disease, with clinical benefits on symptoms which have recently been demonstrated in a clinical study.

Allergens↗

Bronchial challenge tests in patients with asthma sensitized to cats: the importance of large particles in the immediate response.

Our aim was to compare bronchial responses to major cat allergen (Fel d 1) in individuals with intermittent asthma sensitized to cats (19 subjects) according to the droplet particle size. We used three nebulizers, which delivered particles with mass median aerodynamic diameters of 1.4, 4.8, and 10.3 microm. A dosimeter nebulizer was used. The cat allergen was diluted to obtain the same amount of Fel d 1 per puff with each nebulizer. Each patient underwent three methacholine bronchial challenge tests (BCT), each followed 24 hours later by a cat allergen BCT, each performed with a different nebulizer (randomly selected each time, with patient and tester always blinded). Subjects did not differ for methacholine responsiveness, FEV1, mean forced expiratory flow during the middle half of the FVC (FEF25-75), PEF, or dyspnea (Borg scale) before any of the three cat BCTs. Cat allergen PD20 was 271 ng of Fel d 1 with the 1.4 microm nebulizer, 46 ng with the 4.8 microm nebulizer, and 13.5 ng with the 10.3 microm nebulizer (p = 0.00001). Inhalation of small particles (1.4 microm) resulted in significantly lower FEF25-75 24 hours after provocation than large particles did. In conclusion, immediate bronchial response appears to be localized in large airways, and the use of large particles is more appropriate for cat allergen BCTs.

Adult↗

Controlling indoor allergens.

PURPOSE OF REVIEW: Epidemiological surveys indicate that there has been a notable increase in the prevalence of asthma and other allergic diseases in children and adults. The purpose of this review is to report and comment on recent studies about the role of allergen in primary prevention and to seek new insights on the effects of allergen control in allergic patients. RECENT FINDINGS: This paper deals with allergen reduction in primary prevention, the effect of early exposure to pets on atopic diseases and the development of new occupational activity improving allergen control in allergic patients. SUMMARY: The role of allergen dose involved in the onset of atopy is controversial. Studies hypothesizing that a reduction of allergen dose might reduce atopy failed to confirm the data from the Isle of Wight study and found no effect on the frequency of immunoglobulin E sensitization. This effect might nonetheless occur later in life. Other studies indicate that high doses of allergen early in life have a protective effect against cat and dog sensitization. Only one retrospective study found that cat exposure was protective against cat sensitization. A German prospective study suggested, however, that it is more probable that cat allergen exposure is harmfully related to sensitization, by increasing IgE synthesis. The effect of high doses must be clarified by further prospective studies. Accordingly, we must be very careful when giving advice on primary prevention, particularly about the protective effect of cat and dog allergens. Secondary prevention may be dramatically improved with the help of a new occupational activity: the medical indoor environment counsellor.

Air Pollutants↗