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AbstractObjective: Subnormal hypothalamic-pituitary-adrenal (HPA) function and rare cases of adrenal crisis have been reported in asthmatic children treated with inhaled corticosteroids. We investigated subnormal HPA activity and followed up affected patients until recovery of normal HPA functions. Study Design: 100 children with persistent asthma underwent low-dose corticotropin testing, with the administration of 1 μg of 1–24 ACTH intravenously. Treatments were beclomethasone dipropionate as a metered-dose inhaler, n = 14, budesonide as a dry-powder inhaler, n = 16, fluticasone propionate as a metered-dose inhaler n = 31 or a dry-powder inhaler n = 39. The mean commercially labelled dose was 520 ± 29 μg/day (mean ± SEM, range: 160–1,000) and the equipotent dose (which compares the efficiency of these drugs for treating asthma and their responsibility for systemic effects) was 890 ± 55 μg/day (range: 200–2,000). Results: The mean stimulated cortisol level ± SEM (and range) of the patient was 482 ± 12 (148–801), and that of 40 age-matched controls was 580 ± 12.5 (439–726), (SD = 79). The result was subnormal (more than 2 SD below the mean of the controls) in28 of the 100 patients. One–four stepwise decreases of 10–100% in the daily equipotent doses received by the patients with abnormal low-dose corticotropin testing results led to normal results in subsequent low-dose corticotropin testing in 27 retested patients. The mean time interval between two tests was 5 months (range: 2–6 months) and the mean period required for normalization of the test was 13 months (range: 2–21). Only one case of asthma exacerbation and no adrenal crisis were observed over these periods. Conclusions: Decreasing daily equipotent doses led to recovery of normal HPA function without asthma exacerbation. Thus, a revision of the doses of inhaled corticosteroids used in asthmatic children with a progressive decrease to the consensus-recommended doses should decrease the systemic effects of inhaled corticosteroids, while minimizing the risk of asthma exacerbation.Copyright © 2006 S. Karger AG, Basel

Dans les pays industrialise´s, la pre´valence des maladies allergiques s'est conside´rablement accrue au cours de ces 20 dernie`res anne´es. L'augmentation de la teneur en allerge`nes joue un ro^le de´terminant dans ce phe´nome`ne. Pour lutter contre la composante allergique de l'asthme, les moyens the´rapeutiques a` notre disposition sont l'e´viction des allerge`nes et l'immunothe´rapie spe´cifique. L'immunothe´rapie spe´cifique en modifiant la re´ponse Th1/Th2 vis-a`-vis des allerge`nes, pourrait re´duire la destruction de l'e´pithe´lium respiratoire et le remodelage tissulaire conse´cutif a` l'inflammation bronchique chronique d'origine allergique. Dans cette indication, l'immunothe´rapie spe´cifique interviendrait non pas seulement comme une de´sensibilisation spe´cifique mais comme un vaccin anti-allergique. L'efficacite´ d'une immunothe´rapie spe´cifique repose sur des indications bien pose´es mais e´galement sur la qualite´ des extraits allerge´niques utilise´s. Cependant une allerge´nicite´ forte augmente le risque de re´actions anaphylactiques graves, ce qui rend compte de certaines re´ticences a` la pratique de l'immunothe´rapie spe´cifique dans l'asthme de l'enfant. Les manipulations ge´ne´tiques (fragments d'ADN codant pour des allerge`nes inse´re´s dans des plasmides ou des vecteurs viraux) ou l'utilisation des prote´ines allerge´niques (isoallerge`nes, peptides recombinants) vont permettre dans l'avenir d'assurer les deux exigences de l'immunothe´rapie spe´cifique : purete´ et stabilite´ des allerge`nes d'une part et diminution du risque anaphylactique d'autre part. La voie sublinguale est une alternative actuelle a` la voie injectable. Si son innocuite´ est de´montre´e, des e´tudes comparatives a` trois bras avec la voie injectable et un placebo sont ne´cessaires pour affirmer son efficacite´ dans l'asthme de l'enfant. Finalement l'enjeu de l'immunothe´rapie spe´cifique est de modifier l'histoire naturelle de la maladie, en se comportant comme une vaccination.

Proteinase 3 (PR3), a serine proteinase which can degrade lung tissue, is present in the cystic fibrosis (CF) sputum. In the present study, PR3 protein and mRNA expression was determined in circulating neutrophils and monocytes. CF neutrophils contained similar PR3 concentrations as healthy controls and poorly expressed PR3 mRNA. In contrast, CF monocytes showed significantly higher PR3 concentrations than controls, together with an upregulation of PR3 mRNA expression especially during pulmonary exacerbation. Interestingly, antibiotic treatment fully abrogated PR3 mRNA expression and decreased PR3 protein in monocytes. Our findings highlight a potential role of monocyte‐derived PR3 in CF‐associated airway inflammation.

Proteinase 3 (PR3), a serine proteinase which can degrade lung tissue, is present in the cystic fibrosis (CF) sputum. In the present study, PR3 protein and mRNA expression was determined in circulating neutrophils and monocytes. CF neutrophils contained similar PR3 concentrations as healthy controls and poorly expressed PR3 mRNA. In contrast, CF monocytes showed significantly higher PR3 concentrations than controls, together with an upregulation of PR3 mRNA expression especially during pulmonary exacerbation. Interestingly, antibiotic treatment fully abrogated PR3 mRNA expression and decreased PR3 protein in monocytes. Our findings highlight a potential role of monocyte-derived PR3 in CF-associated airway inflammation.

We measured personal exposure to nitrogen dioxide (NO2), nitrogen monoxide (NO), and ozone (O3), using personal passive samplers during three 4-day periods, in a panel study of asthmatics continuing the normal activities of everyday life. Fifty-five adults, mean age 42 years, 53% men, and 39 children, mean age 11 years, 67% boys, wore two Ogawa passive samplers simultaneously: one for O3, the other for NO2and NO. Mean outdoor pollution was measured at a regional monitoring network. Personal exposure levels were scattered; they were (on average) higher than stationary-site levels for NO and lower for NO2and O3. In adults, 41% of the variance of personal exposure to NO2was explained by mean stationary-site measurement levels (P<0.0001). Twenty-one percent additional variance was explained by living near a main road, not having an extractor fan over the cooker, older age, and male sex. NO and O3personal exposures correlated poorly with stationary-site measurements. In panel studies of the health effects of air pollution, personal exposure to NO2and NO can be measured satisfactorily by passive samplers: such measurements are necessary for NO but not for NO2. For O3, accurate personal exposure measurement remains a challenge and further technical development is required.

ABSTRACT: The predominant inflammatory cell type within the alveolar structure in bronchopulmonary dysplasia (BPD) is the alveolar macrophage (AM). AM ability to release hydrogen peroxide, a way to evaluate the cell status, was studied in nine infants who developed clinical and radiological evidence of BPD, and was compared to those from infants without lung parenchymal disorders (n = 6). AM were collected by bronchoalveolar lavage which was done after the mechanical ventilation stage in the BPD group. The experiments were performed on unstimulated AM and on AM stimulated by phorbol myristate acetate. Results revealed that the amount of hydrogen peroxide accumulated in the culture medium was significantly enhanced in the BPD group, in both experimental conditions (p < 0.01 and < 0.001, respectively). Furthermore, improvement of patients treated with glucocorticoids was closely related to a reduction of the alveolitis with a decrease of AM ability to generate hydrogen peroxide. These data indicate that AM activation is a central component of alveolitis in BPD and that extracellular production of oxidants by stimulated AM may play a critical role in the pathogenesis of the disease.

SummaryTo evaluate the contribution of energy expenditure to the energy imbalance seen in cystic fibrosis patients, resting energy expenditure was measured using open-circuit indirect calorimetry in eight infants with cystic fibrosis, aged 2–7 months (mean, 4), without overt lung disease and in 10 healthy age-matched controls. In both groups, we found close, significant, linear correlations between resting energy expenditure and body weight and between resting energy expenditure and fat-free mass as measured by anthropometry. Cystic fibrosis patients had a 26 increase in resting energy expenditure per kilogram of fat-free mass as compared with controls and a 32 increase in resting energy expenditure as compared with predicted values for fat-free mass. These data from young infants free of clinical symptoms suggest a constitutional metabolic disorder in cystic fibrosis and support the need for early nutritional therapy in cystic fibrosis patients.

The predominant inflammatory cell type within the alveolar structure in bronchopulmonary dysplasia (BPD) is the alveolar macrophage (AM). AM ability to release hydrogen peroxide, a way to evaluate the cell status, was studied in nine infants who developed clinical and radiological evidence of BPD, and was compared to those from infants without lung parenchymal disorders (n= 6). AM were collected by bronchoalveolar lavage which was done after the mechanical ventilation stage in the BPD group. The experiments were performed on unstimulated AM and on AM stimulated by phorbol myristate acetate. Results revealed that the amount of hydrogen peroxide accumulated in the culture medium was significantly enhanced in the BPD group, in both experimental conditions (p< 0.01 and < 0.001, respectively). Furthermore, improvement of patients treated with glucocorticoids was closely related to a reduction of the alveolitis with a decrease of AM ability to generate hydrogen peroxide. These data indicate that AM activation is a central component of alveolitis in BPD and that extracellular production of oxidants by stimulated AM may play a critical role in the pathogenesis of the disease.

SummaryTo evaluate the contribution of energy expenditure to the energy imbalance seen in cystic fibrosis patients, resting energy expenditure was measured using open-circuit indirect calorimetry in eight infants with cystic fibrosis, aged 2–7 months (mean, 4), without overt lung disease and in 10 healthy age-matched controls. In both groups, we found close, significant, linear correlations between resting energy expenditure and body weight and between resting energy expenditure and fat-free mass as measured by anthropometry. Cystic fibrosis patients had a 26% increase in resting energy expenditure per kilogram of fat-free mass as compared with controls and a 32% increase in resting energy expenditure as compared with predicted values for fat-free mass. These data from young infants free of clinical symptoms suggest a constitutional metabolic disorder in cystic fibrosis and support the need for early nutritional therapy in cystic fibrosis patients.

To evaluate the relationship between clinical parameters and differential cell counts, bronchoalveolar lavage was performed in 79 asthmatic infants and children with unusual asthma. Multivariate analysis showed significant associations between (1) allergic asthma and the presence of alveolar eosinophils and (2) persistent and longer asthma and an increased number of alveolar neutrophils. Our results provide the first evidence that in asthmatic infants and children eosinophilic inflammation is related to allergic sensitization. (J Allergy Clin Immunol 2002;110:42-4.)

• Kaposi's sarcoma has only rarely been reported in children with acquired immunodeficiency syndrome. In contrast to adult patients, in whom the disease is predominantly cutaneous, among pediatric patients with acquired immunodeficiency syndrome, Kaposi's sarcoma is primarily limited to the lymphadenopathic form. We describe two children with the acquired immunodeficiency syndrome who developed diffuse nodular skin lesions of Kaposi's sarcoma.(Arch Dermatol. 1990;126:791-793)

In urban areas, outdoor air pollutants such as particulate matter (PM) are suspected to induce harmful effects on respiratory health, rising the question of their involvement in allergic asthma and rhinitis, two inflammatory diseases. In the present study, the potential effect of the personal exposure to two major outdoor pollutants resulting from vehicle emissions, PM2.5 (diameter less than 2.5 µm) and nitrogen oxides (NOx) on nasal inflammatory biomarkers was examined in healthy and asthmatic allergic children living in Paris area.

Summary: Children are exposed to indoor and outdoor air pollution. Whereas normal children can suffer such air condition without long term sequellae, other children at risk can develop, since infancy, bronchopulmonary disease either because of bad conditions of life or congenital or hereditary causes.

Fifteen infants with acute pneumonia, mean age 11 months (Group I) and 24 immuno-depressed (ID) children with severe interstitial pneumonitis, mean age 8 1/2 years (Group II) were studied using broncho-alveolar lavage (BAL). Each BAL fluid (F) examination comprised : 1) cytological examination (CE) 2) virological study 3) total proteins (TP) and Ig classes (G, A, M) concentrations quantification. Specific activity (Act) of anti-cytomegalovirus (CMV) Ig anti bodies (Ab) was titrated simultaneously in BALF and sera by ELISA method, only in ID. Group I : 7 viruses were isolated : para influenza type 1 (1), 3 (1), adenoV type 1 (1), 2 (1), 6 (1), RSV (2) ; CE was normal (4) or showed an increase in polymorphonuclears (PN) (2) or lymphocytes (L) count (C). Group II : 2 viruses were isolated : measles (1) RSV (1) with increase in PNC and in IgG/TP ratio ; in 2 other cases (with bone marrow transplantation) o local pulmonary production of anti CMV IgG/Ab was observed (increase in BALF Act/sera Act ratio) with LC increase.In conclusion BAL in children is a safe productive mean in diagnosis of virus infection responsible for severe pneumonitis and reveals a local correlative increase in PNC or LC and IgG production.