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Biomedical subjects

Pierre Scheinmann

Publications and source records attributed to Pierre Scheinmann.

At least 19 recordsLinked to original sources

Nitric oxide in children with persistent asthma.

OBJECTIVE: To assess the difference in exhaled nitric oxide levels in atopic and nonatopic asthmatic patients treated with anti-inflammatory drugs, and to compare exhaled nitric oxide measurement with lung function tests. METHODS: Cross-sectional study with 45 consecutively selected patients with moderate and severe persistent asthma, aged between 6 and 17 years, and treated with anti-inflammatory drugs for at least 1 year. The patients were split into two groups: atopic ones (with positive skin tests) and nonatopic ones. The clinical and functional assessments and the measurement of exhaled nitric oxide were carried out concomitantly. RESULTS: There was a male predominance (62.5%), with an age range between 6 and 13 years (mean of 10.4 years) in 85% of the patients. Neither the symptoms associated with asthma (p = 0.07), allergic rhinitis (p = 0.17), food allergy (p = 0.09), necessity of systemic corticosteroids (p = 0.10), antileukotrienes (p = 0.20) and antihistamines (p = 0.70), nor the three parameters used to assess lung function (FEV(1), FEV(1)/FVC and FEF(25-75%), p > or = 0.14) were statistically significant. The frequency of eczema (p < 0.005) and exhaled nitric oxide levels (p < 0.001) were higher among atopic patients. CONCLUSION: Results suggest that clinical and functional stability of asthma among atopic patients does not necessarily reflect an efficient control over the inflammatory process and a higher probability for recurrence after discontinuation of anti-inflammatory therapy.

Administration, Inhalation↗

Microbiological diagnosis of empyema in children: comparative evaluations by culture, polymerase chain reaction, and pneumococcal antigen detection in pleural fluids.

BACKGROUND: Pleural empyema is an increasingly reported complication of pneumonia in children. Microbiological diagnostic tests for empyema by culture frequently have false-negative results due to previous administration of antibiotics. Molecular diagnosis by broad-range 16S ribosomal DNA (rDNA) polymerase chain reaction (PCR) and rapid pneumococcal antigen detection are reliable tools, but their diagnostic value has not been clearly established for pleural fluid samples. Pneumococcal antigen detection has only been validated for urine and cerebrospinal fluid samples. METHODS: Over 4 years, pleural fluid specimens were collected from 78 children with pleural empyema. Standard culture, pneumococcal antigen detection by latex agglutination (Pastorex; Bio-Rad) and immunochromatographic testing (Binax NOW Streptococcus pneumoniae), and 16S rDNA PCR were performed on these specimens. Pneumococcal identification by 16S rDNA PCR and sequencing was confirmed by pneumolysin PCR. RESULTS: Of the 78 cases of pleural empyema, 60 (77%) were microbiologically documented by culture or 16S rDNA PCR. Of the 40 pneumococcal empyema cases, 17 (43%) were only diagnosed by PCR and 23 with PCR and culture. The sensitivity and specificity of the latex antigen detection (with the use of culture and/or PCR as the test standard) were 90% and 95%, respectively. The immunochromatographic test detected pneumococcal antigens in 3 additional specimens for which latex agglutination results were negative, thereby increasing the sensitivity of antigen detection. CONCLUSIONS: Pneumococcal antigen detection in pleural fluid specimens from children provides a rapid and sensitive method of diagnosis of pneumococcal empyema, which can be confirmed by specific pneumolysin PCR when culture results are negative. Broad-range 16S rDNA PCR has value in detecting bacterial agents responsible for culture-negative pleural empyema.

Antigens, Bacterial↗

DC-SIGN induction in alveolar macrophages defines privileged target host cells for mycobacteria in patients with tuberculosis.

BACKGROUND: Interplays between Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) in human and host professional phagocytes, namely macrophages (Mphis) and dendritic cells (DCs), are central to immune protection against TB and to TB pathogenesis. We and others have recently shown that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN; CD209) mediates important interactions between mycobacteria and human monocyte-derived DCs (MoDCs) in vitro. METHODS AND FINDINGS: In order to explore the possible role of DC-SIGN in M. tuberculosis infection in vivo, we have analysed DC-SIGN expression in broncho-alveolar lavage (BAL) cells from patients with TB (n = 40) or with other non-mycobacterial lung pathologies, namely asthma (n = 14) and sarcoidosis (n = 11), as well as from control individuals (n = 9). We show that in patients with TB, up to 70% of alveolar Mphis express DC-SIGN. By contrast, the lectin is barely detected in alveolar Mphis from all other individuals. Flow cytometry, RT-PCR, and enzyme-linked immunosorbent assay analyses of BAL-derived fluids and cells indicated that M. tuberculosis infection induces DC-SIGN expression in alveolar Mphis by a mechanism that is independent of Toll-like receptor-4, interleukin (IL)-4, and IL-13. This mechanism most likely relies on the secretion of soluble host and/or mycobacterial factors that have yet to be identified, as both infected and uninfected bystander Mphis were found to express DC-SIGN in the presence of M. tuberculosis. Immunohistochemical examination of lung biopsy samples from patients with TB showed that the bacilli concentrate in pulmonary regions enriched in DC-SIGN-expressing alveolar Mphis in vivo. Ex vivo binding and inhibition of binding experiments further revealed that DC-SIGN-expressing alveolar Mphis constitute preferential target cells for M. tuberculosis, as compared to their DC-SIGN- counterparts. In contrast with what has been reported previously in MoDCs in vitro, ex vivo DC-SIGN ligation by mycobacterial products failed to induce IL-10 secretion by alveolar Mphis, and IL-10 was not detected in BALs from patients with TB. CONCLUSION: Altogether, our results provide further evidence for an important role of DC-SIGN during TB in humans. DC-SIGN induction in alveolar Mphis may have important consequences on lung colonization by the tubercle bacillus, and on pulmonary inflammatory and immune responses in the infected host.

Case-Control Studies↗

Foreign body aspiration: clinical, radiological findings and factors associated with its late removal.

OBJECTIVE: The study was carried out to assess the clinical and radiological findings and factors related to delay in definite diagnosis of foreign body aspiration and its removal. METHODS: Medical charts of 280 bronchoscopic-proven foreign body (FB) inhalators were reviewed. To analyze factors related to late removal, the population studied was divided into two groups according to time elapsed between injury and care-seeking (up to 24h and longer than 24h) followed by FB removal. RESULTS: Most children (69.5%) were under three, most were males (63.1%) and in 47.5%, rigid bronchoscopy was performed 24h after the accident. Organic foreign bodies were found in 63.4% of cases, most frequently peanuts (20.5%). Mortality related to FB aspiration reached 0.7%. In comparison with endoscopic diagnosis, clinical and radiological abnormalities were found in 99.3 and 84.3% (95% CI, 79.5-88.4%) of studied patients, respectively. The number of health services sought until definite diagnosis was the only factor associated with late removal (OR=23.0, 95% CI, 10.7-49.3%, p<0.001). CONCLUSION: The population studied presented a long delay in FB removal, thus demanding actions enhancing parent, physician and health services awareness, aiming at an earlier referral for diagnostic and therapeutic bronchoscopy.

Age Distribution↗

High-resolution computed tomography scan and airway remodeling in children with severe asthma.

BACKGROUND: Children with severe asthma have a significantly higher bronchial wall thickness (BWT) on high-resolution computed tomography scan than control children. OBJECTIVE: We sought to determine whether a BWT score correlates with markers of airway remodeling and inflammation. METHODS: In 37 children with severe asthma, we determined reticular basement membrane thickness; number of intraepithelial neutrophils and eosinophils on bronchial biopsy; IFN-gamma, IL-4, IL-5, and eosinophil cationic protein levels and IFN-gamma/IL-4 ratio on bronchoalveolar lavage specimen; and alveolar nitric oxide (NO) concentration and the maximum airway wall NO flux. RESULTS: The BWT score significantly correlated with reticular basement membrane thickening (r = 0.34; P = .04) and NO production by the airway wall (r = 0.45; P = .02). The correlation with the eosinophil cationic protein level was just significant (r = 0.40; P = .05), whereas there was no correlation with IFN-gamma/IL-4 ratio (r = -0.31; P = .08). The BWT score did not correlate with FEV(1) or forced expiratory flow at 25% to 75% of forced vital capacity. CONCLUSION: High-resolution computed tomography scan is a noninvasive technique that might be valuable for quantifying airway remodeling in children with severe asthma. The new generations of multislice computed tomography scanners will allow higher definition and lower radiation exposure and probably give a better assessment of airway remodeling and efficacy of treatment in children with asthma.

Adolescent↗

Difficult asthma in children: an analysis of airway inflammation.

BACKGROUND: Difficult asthma in children displays distinct clinical patterns, and its physiopathology remains poorly understood. OBJECTIVE: To determine the characteristics of the bronchial inflammatory profile in children with difficult asthma. METHODS: We performed endobronchial biopsy and bronchoalveolar lavage in 28 children with persistent bronchial obstruction despite high doses of inhaled corticosteroids and regular treatment with long-acting beta(2)-agonists: 13 had persistent symptoms and 15 had few or no symptoms. RESULTS: The number of eosinophils (P =.03) and neutrophils (P =.04) in the epithelium was significantly higher in symptomatic children than in children with few symptoms. Reticular basement membrane thicknening was similar in both groups. IFNgamma levels (P =.03) and IFNgamma/IL-4 ratio (P =.01) were significantly higher in children with few symptoms. CONCLUSIONS: In symptomatic children, T(H)2-type inflammation was associated with the presence of activated eosinophils in the epithelium, whereas asthma in children with few symptoms was associated with an increase in T(H)1 cytokine levels. The high levels of IFNgamma suggest that this T(H)1 cytokine may modulate the local inflammatory response.

Asthma↗

Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies.

Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.

Anti-Allergic Agents↗

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis.

BACKGROUND: This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. OBJECTIVE: This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. METHODS: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point. RESULTS: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P </=.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P <.05), including nasal congestion in the evening reflective assessment (P <.05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality. CONCLUSION: The efficacy and safety of the H(1)-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis.

Anti-Allergic Agents↗

Mycobacterium abscessus and children with cystic fibrosis.

We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5-22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including 10 with >3 positive samples (versus 3 patients for M. avium complex). The M. abscessus isolates from 14 patients were typed by pulsed-field gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out a common environmental reservoir or person-to-person transmission. Water samples collected in the cystic fibrosis center were negative for M. abscessus. This major mycobacterial pathogen in children and teenagers with cystic fibrosis does not appear to be acquired nosocomially.

Adolescent↗

Rib fractures after chest physiotherapy for bronchiolitis or pneumonia in infants.

BACKGROUND: The reported causes of rib fractures in infants are: child abuse, accidental injury, cardiopulmonary resuscitation, bone fragility, birth trauma and severe cough. OBJECTIVE: To report chest physiotherapy (CPT) as a new cause of rib fractures in five infants. MATERIALS AND METHODS: We retrospectively identified all infants with rib fractures after CPT for bronchiolitis or pneumonia over a 4-year period in two paediatric and one paediatric radiology units in three university hospitals in Paris. RESULTS: Five boys were identified. Their median age was 3 months. None had any other potential cause of rib fractures. The indication for CPT was bronchiolitis in four cases and pneumonia in one. The median number of rib fractures was four (range 1-5). Fractures were located between the 3rd and 8th ribs; they were lateral in four patients and posterior in one; they were unilateral in four patients and bilateral in one. Evolution was favourable in all cases. The prevalence of rib fractures after CPT during the study period was estimated at 1 in 1,000 infants hospitalised for bronchiolitis or pneumonia. CONCLUSIONS: CPT should be considered a potential, but very rare cause of rib fractures in infants. It can be of clinical relevance when rib fractures are the only feature suggestive of child abuse.

Bronchiolitis↗

Bronchoalveolar cells in children < 3 years old with severe recurrent wheezing.

STUDY OBJECTIVE: To determine the cell profile of BAL from infants with severe recurrent wheezing who were not acutely ill at the time of investigation, suggesting an ongoing inflammation. DESIGN AND PATIENTS: In a retrospective study, we determined BAL cell profiles for 83 children with wheezing aged 4 to 32 months (mean +/- SD, 11.3 +/- 5.5 months). Fiberoptic bronchoscopy was performed in children with severe recurrent wheezy bronchitis unresponsive to inhaled steroids. These children were compared with 17 children aged 6 to 36 months (mean, 15.1 +/- 7.5 months) with various nonwheezing pulmonary diseases. Children were included as control subjects if they had no endobronchial inflammation and no atopy. RESULTS: The BAL cell profile of young children with wheezing typically includes a significantly higher cell count (mean, 644.4 +/- 956.8 x 10(3)/mL vs 313 +/- 203.2 x 10(3)/mL, p = 0.008), a significantly higher percentage of neutrophils (mean, 9 +/- 12.1% vs 2.1 +/- 2.2%, p = 0.003), and a higher neutrophil count (mean, 43.2 +/- 81.6 x 10(3)/mL vs 7.9 +/- 11.8 x 10(3)/mL, p = 0.003), as compared with control subjects. The larger number of neutrophils in children with wheezing was not correlated with bacterial or viral infection, or with age, sex, or atopic status. In contrast to the situation in asthmatic adults, eosinophil levels were not higher in children with wheezing than in control subjects (mean, 0.09 +/- 0.27% vs 0.08 +/- 0.25%). CONCLUSION: Neutrophil-mediated inflammation in the airways appears to better characterize severe recurrent wheezing in children < 3 years old.

Adult↗

Thoracic CT in pediatric patients with difficult-to-treat asthma.

OBJECTIVE: . The aim of this study was to establish objective, simple criteria for bronchial wall thickening in children with difficult-to-treat asthma. SUBJECTS AND METHODS: . Bronchial sections were counted at five levels in both lungs and at three levels in the right lung on high-resolution CT and plotted against lung function. Findings from 27 children with persistent symptoms of asthma (mean age, 11.4 years; SD, +/-3.1 years) that were severe (group A, n = 15) or moderate (group B, n = 12) were compared with findings from 21 control subjects (mean age, 10.8 years; SD, +/-3.0 years) using the Student's t test, analysis of variance, and Dunn-Bonferroni test. RESULTS: . A bronchial wall thickening score based on the number of visible bronchi at three levels (three-level score) proved to be as valuable as and simpler to obtain than a score based on the number of bronchi at five levels (five-level score). The three-level scores for groups A and B were similar (mean +/- SD, 16.8 +/- 4.2 vs 18.4 +/- 3.4, respectively; p = not significant), but these scores were significantly higher than those for the control subjects (mean +/- SD, 8.2 +/- 3.4, respectively; p < 0.001). There was no correlation between the three-level score and forced expiratory volume in 1 sec or forced expiratory flow between 25% and 75% of forced vital capacity. In contrast with adults with severe asthma, our pediatric patients with difficult-to-treat asthma did not have CT evidence of mucoid impaction, emphysema, areas of hyperlucency, bronchiectasis, or sequellar line shadows. CONCLUSION: . Bronchial wall thickening visible on high-resolution CT may constitute an additional criterion of asthma severity in children. CT evidence of bronchial wall thickening might help to identify patients with a higher risk of airway remodeling.

Adolescent↗

Psychopathology and quality of life for adolescents with asthma and their parents.

Asthma is known to have a direct impact on the quality of life of children with asthma and their families as a consequence of the attacks on day-to-day life. Psychopathological factors may be associated with poor quality of life by modulating the handicap and the patient's experience of it. The authors' objective was to evaluate the relationship between emotional and behavioral problems and quality of life, as assessed by the Pediatric Asthma Quality of Life Questionnaire and the Pediatric Asthma Caregiver's Quality of Life Questionnaire. The study group consisted of 100 adolescent outpatients with asthma who were undergoing regular checkups: 70 boys and 30 girls, ages 12 to 19. They were evaluated by means of self-administered questionnaires completed by their parents. Path analysis was used to propose a model of relationships between psychopathology and quality of life. The quality of life of the children with asthma and their parents was clearly associated with the presence or absence of psychological problems in the patients. Emotional problems were associated with the quality of life of both the patients and their parents; behavioral problems had a smaller effect on the quality of life of the parents only. The authors proposed a structural model of the quality of life of adolescents with asthma and their parents in which quality of life is dependent on psychological variables and is responsible for emotional problems. Multivariate analyses indicated that the quality of life of the children with asthma and their parents and the correlation between quality of life and psychopathology depended little on medical variables such as the duration of illness, its pretreatment severity, or hospitalizations in the past year. In contrast, the quality of life of the parents depended on that of the children and vice versa. This study showed that scores on the Pediatric Asthma Quality of Life Questionnaire and the Pediatric Asthma Caregiver's Quality of Life Questionnaire reflected not only the medical status of the patients but also psychological variables, which appeared to be a consequence of the functional handicap associated with asthma. Patients who assess the quality of their lives as poor would benefit from psychological evaluation and support.

Adolescent↗

Vaccine allergy and pseudo-allergy.

Allergic and pseudo-allergic reactions to vaccines frequently involve the skin, and can be generalized systemic symptoms (urticaria/angioedema, serum sickness, flares of eczema) or localized at the sites of vaccination (persistent nodules, abcesses, granulomas). Diagnosis of Arthus-type reactions is based on clinical history and specific IgM/IgG anti-toxoid determination. For other local reactions, diagnostic value of non-immediate responses in skin tests varies with clinical symptoms and substances involved. Immediate responses in skin tests and specific IgE determination have good diagnostic and/or predictive value in anaphylaxis and immediate/accelerated urticaria/angioedema to toxoid-, pneumococcus-, and egg- and gelatin-containing vaccines. Diagnosis of reactions to dextran in BCG is based on specific IgM/IgG determination. Most non-immediate generalized reactions result from non-specific inflammation, except for gelatin-containing vaccines, but the diagnostic value of immuno-allergological tests with the vaccines and gelatin are controversial. Withholding booster injections is advised if specific IgM/IgG levels are high. If the levels are low, sequential injections of vaccines containing a single vaccinating agent are usually tolerated. However, injections of the vaccine should be performed using a " desensitization " procedure in patients reporting anaphylaxis and immediate/accelerated urticaria/angioedema.

Anaphylaxis↗