Time course of serum inhibitory activity for facilitated allergen-IgE binding during bee venom immunotherapy in children.

BACKGROUND: Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen-IgE complexes to B cells. As this 'functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal. METHODS: Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age- and gender-matched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay. RESULTS: Sera obtained during VIT significantly inhibited allergen-IgE binding to B-cells (pre-treatment=104+/-23%; 2 years=46+/-15%; P<0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment=8.6+/-2.3 AU; 2 years=26.7+/-3.5 AU; P<0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44+/-7 AU) in sera obtained after 2 years of VIT (25+/-5 AU; P<0.01) and 2 years following the withdrawal of VIT (10+/-3 AU; P<0.05). CONCLUSIONS: In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels, rather than serum inhibitory activity for FAB, may be more relevant for long-term clinical efficacy of VIT.

Arthralgia and digital clubbing in a child: hypertrophic osteoarthropathy with inflammatory pseudotumour of the lung.

Arthralgia in childhood is an unspecific symptom. One rare cause of arthralgia is hypertrophic osteoarthropathy associated with digital clubbing. We present a child where hypertrophic osteoarthropathy led to the rare diagnosis of an inflammatory pseudotumour of the lung. In a 12-year-old girl with arthralgia and digital clubbing, a chest radiograph disclosed a large round mass in the right upper lobe, and the following chest computed tomography scan showed a large solid homogenous, round, well marginated lesion with little contrast enhancement. A lobectomy of the right upper lobe was performed, and histological examination showed an inflammatory pseudotumour. The postoperative course was without problems: arthralgia and digital clubbing disappeared.

Partial splenectomy in cystic fibrosis patients with hypersplenism.

We report three cystic fibrosis (CF) patients with hypersplenism who underwent partial splenectomy. The postoperative course was uneventful in two patients; one patient developed a complication necessitating resection of the rest of the spleen. Haematological parameters improved and oesophageal varices regressed in all patients. On follow up, one patient showed a normal spleen, the other a normally functioning accessory spleen; the third patient again developed splenomegaly with hypersplenism. Partial splenectomy is a promising therapeutic option for CF patients with hypersplenism.

Effects of nedocromil and salbutamol on airway reactivity in children with asthma.

Nedocromil and salbutamol are effective drugs in preventing exercise-induced asthma (EIA). The aim of this study was to compare the protective effects of both drugs and a combination of both drugs against cold dry air-induced bronchoconstriction, using cold dry air challenges (CACh) as a surrogate for exercise. Twenty-five atopic children (mean age 13.7, range 8-18 yrs) with EIA participated in the study. Lung function tests were performed before medication, 30 min after medication and just before CACh, and 3 and 15 min after the challenge on four consecutive days. CACh consisted of a 4-min isocapnic hyperpnoea of -10 degrees C, absolutely dry air. Treatment consisted of nedocromil (two puffs of 2 mg) plus placebo, salbutamol (two puffs of 100 microg) plus placebo, the combination of both drugs, and placebo alone, in a random order. Both active drugs were significantly more protective than placebo and the combination showed an additive effect. Mean maximum postchallenge decrease in forced expiratory volume in one second after placebo was 27+/-8.1%, 12+/-9.5% after nedocromil, 8+/-10.4% after salbutamol, and 4.5+/-6.71% after the combination of both drugs, respectively. These results suggest that both drugs protect against exercise-induced asthma. Although not as effective as salbutamol and combined medication, nedocromil can give sufficient protection for many patients.

Laser acupuncture in children and adolescents with exercise induced asthma.

BACKGROUND: Laser acupuncture, a painless technique, is a widely used alternative treatment method for childhood asthma, although its efficacy has not been proved in controlled clinical studies. METHODS: A double blind, placebo controlled, crossover study was performed to investigate the possible protective effect of a single laser acupuncture treatment on cold dry air hyperventilation induced bronchoconstriction in 44 children and adolescents of mean age 11.9 years (range 7.5-16.7) with exercise induced asthma. Laser acupuncture was performed on real and placebo points in random order on two consecutive days. Lung function was measured before laser acupuncture, immediately after laser acupuncture (just before cold dry air challenge (CACh)), and 3 and 15 minutes after CACh. CACh consisted of a 4 minute isocapnic hyperventilation of -10 degrees C absolute dry air. RESULTS: Comparison of real acupuncture with placebo acupuncture showed no significant differences in the mean maximum CACh induced decrease in forced expiratory volume in 1 second (27.2 (18.2)% v 23.8 (16.2)%) and maximal expiratory flow at 25% remaining vital capacity (51.6 (20.8)% v 44.4 (22.3)%). CONCLUSIONS: A single laser acupuncture treatment offers no protection against exercise induced bronchoconstriction in paediatric and adolescent patients.

Clinical and histopathological findings in two Turkish children with follicular bronchiolitis.

UNLABELLED: We report on two Turkish children who presented with progressive airway obstruction. Open lung biopsy revealed follicular bronchiolitis. The children were treated with systemic steroids and various topical medications. Whereas the respiratory situation of patient 1 required immunosuppressive therapy, the condition of patient 2 stabilised without systemic medication. CONCLUSION: Diagnosis of follicular bronchiolitis should be considered when children present with recurrent respiratory tract infections, progressive dyspnoea, and chronic bronchial obstruction. Children in whom follicular bronchiolitis is suspected should undergo open lung biopsy for confirmation of diagnosis.

[Mucous clearing respiratory-physiotherapy in pediatric pneumology]. / Die sekretfördernde Atemphysiotherapie in der pädiatrischen Pneumologie.

Chest physiotherapy for mucus clearance may be seen as a therapeutic application of respiratory physiology; the basic mechanical principles do not differ between the treatment of paediatric and adult patients. However, children present with a developmentally defined, age-specific situation regarding respiratory structure and function that calls for a specialised therapeutic approach. Inspiration dilates bronchi and thus brings air behind obstructing mucus plugs. Newborns and infants have the special problem of an overly compliant, instable thorax and an easily obstructed upper airway; hence they require special help with lung volume management. Forced expirations mobilise and transport secretions by expiratory airflow in combination with a wave of moving choke points. Early in life, low stability of airways threatens to hamper this mechanism by complete closure; this calls for special therapeutic assistance. Positioning regionally modifies ventilatory excursions and is thus used to target gas-liquid pumping. However, lateral decubitus position does not affect ventilation in children in the same way as in adults. Disease-inflicted changes of structure and function call for further modification of the therapeutic approach. Finally, the psychology of therapist-patient interaction differs substantially between different age groups.

Disseminated cytomegalovirus infection as initial manifestation of hyper-IgM syndrome in a 15-month-old boy.

UNLABELLED: We report on the clinical, laboratory, and molecular genetic findings in a 15-month-old boy who initially presented with disseminated cytomegalovirus and concomitant para-influenza virus infection. Hyper-IgM syndrome, suspected on clinical grounds, was confirmed by immunological investigations. In addition, a previously unreported potentially disease-causing mutation in the CD40 ligand gene was detected in this patient. CONCLUSION: The present case illustrates that disseminated cytomegalovirus infection with atypical clinical features should be included in the spectrum of the hyper-IgM syndrome.

Recurrent lower respiratory tract infections in a 14-year-old boy with tracheobronchomegaly (Mounier-Kuhn syndrome).

Tracheobronchomegaly (Mounier-Kuhn syndrome) is characterized by dilatation of the central airways, tracheobronchial outpouchings, and chronic tracheobronchitis. Most cases are diagnosed in adulthood. We report the clinical, radiographic, and bronchoscopic findings in a 14-year-old boy with tracheobronchomegaly, ptosis of the right eyelid, and redundant skin and mucosa of the upper lip, who presented with a 2-year history of recurrent lower respiratory tract infections. Pediatricians should be aware of the possibility that tracheobronchomegaly may cause clinical symptoms in childhood and adolescence. Pediatr Pulmonol. 2000; 29: 476-479.

Chronic interstitial lung disease due to Epstein-Barr virus infection in two infants.

This case study reports on two infants, 5 and 6 months of age, respectively, with chronic interstitial lung disease who presented with failure to thrive, tachypnoea, rales and mild hypoxaemia. Epstein-Barr virus (EBV) was detected by in situ hybridization in lung biopsy specimens and by EBV-deoxyribonucleic acid-polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) fluid in one patient and by in situ hybridization and PCR analysis in BAL fluid in the second patient. There was serological evidence of immunoglobulin G antibodies to EBV capsid antigen by indirect immunofluorescence in both patients. After 7 months of respiratory symptoms one patient was successfully treated with a 10 day course of intravenous ganciclovir followed by oral acyclovir for 20 days. The other patient became symptom free after 3.5 months of respiratory symptoms, without any specific antiviral medication. During a follow-up of 2 and 1.5 yrs, respectively, both infants remained symptom free and showed normal physical development.

Assessment of bronchodilator responsiveness in infants with bronchiolitis. A comparison of the tidal and the raised volume rapid thoracoabdominal compression technique.

Whether bronchodilators should be used for the treatment of infants with bronchiolitis is subject to debate, partly because of the low sensitivity of the methods for assessing lung function changes in infants. In the present study, we compared the recently introduced raised volume (RVRTC) with the conventional end-tidal rapid thoracoabdominal compression (ETRTC) technique in infants with acute viral bronchiolitis. In 17 infants lung function was assessed by both methods, at baseline values and after salbutamol inhalation. Forced expiratory volumes (FEV(0.5), FEV(0.75), FEV(1.0)) were used for the quantification of RVRTC measurement, and maximal expiratory flow at functional residual capacity (Vmax (FRC)) for ETRTC measurements. A significant individual change was defined by a mean postbronchodilator value that differed from baseline value by more than twice the within-subject coefficient of variation (CV). Group mean intrasubject CVs ranged from 4.7% to 5.3% for FEV parameters; it was 14.0% for Vmax (FRC). For the group, post-bronchodilator measurements did not differ significantly from baseline measurements. For the majority of infants, however, the within-subject comparison of responses revealed substantial differences between both techniques; while no infant demonstrated a significant increase in Vmax (FRC), eight (47%) infants responded with significantly improved timed volumes. The RVRTC technique provides the investigator with a more sensitive diagnostic tool for documenting the effectiveness of therapeutic interventions on an individual basis. Furthermore, the findings of the present study provide a rationale for the application of bronchodilators in a subgroup of infants with acute bronchiolitis.

The physiology of forced expiration.

Insight into the physiology of a forced expiration is the most important prerequisite for understanding and correctly interpreting the most common pulmonary function tests like spirometry and recording of a maximum expiratory flow-volume curve. Along the airway, intraluminal pressure falls progressively from alveolar pressure in the periphery to atmospheric pressure at the airway opening. Downstream of the equal pressure point, where intraluminal equals transthoracic pressure, the airway is dynamically compressed. Once the forced expiration is flow limited, more transthoracic pressure will rather effect more compression than a further increase in flow. It follows that the achieved maximum expiratory flow rates are then exclusively defined by the resistance of the intrathoracic airways and no longer by muscular effort. The end of a forced expiration is determined by the elastic resistance of the thoracic cage and by airway closure.

Reproducibility of forced expiratory flow and volume measurements in infants with bronchiolitis.

The end-tidal rapid thoracoabdominal compression (ETRTC) technique is an established method for lung function testing in infancy. Previous work in healthy infants, however, has shown that measurements with the newly developed raised volume rapid thoracoabdominal compression (RVRTC) technique are more reproducible than those with the ETRTC technique. So far, reproducibility of the two techniques has not been compared in infants with acute airway disease. Twenty-three infants with acute viral bronchiolitis underwent lung function assessment with both the ETRTC and the RVRTC technique. A series of 8-10 measurements with each technique was done in randomized order. Forced expired volumes at 0.5, 0.75, and 1 sec after chest compression (FEV(0.5), FEV(0.75), and FEV(1.0)) were measured with the RVRTC technique; maximum expiratory flow at functional residual capacity (V'(maxFRC)) was measured with the ETRTC technique. Group mean intrasubject coefficients of variation (CV) were 4.84% for FEV(0.5), 5.01% for FEV(0.75), 5.43% for FEV(1. 0), and 13.79% for V'(maxFRC), respectively. Differences between FEV parameters were statistically insignificant, whereas the difference between each FEV parameter and V'(maxFRC) was highly significant (P < 0.001). In infants with acute viral bronchiolitis, RVRTC measurements have significantly less intraindividual variability than flow rates assessed with the conventional ETRTC technique. This finding provides the basis for assessing disease course and effects of therapeutic interventions on an individual basis.

Serum eosinophil cationic protein and bronchial responsiveness in pediatric and adolescent asthma patients.

BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a marker of inflammatory activity in bronchial asthma. Bronchial responsiveness, measured either by inhaling pharmacologically active substances such as histamine or methacholine, or by applying physical stimuli such as the hyperventilation of cold dry air, is also considered to be an indirect marker of bronchial inflammation. OBJECTIVES: In this study, we investigated the possible relationship between serum ECP and bronchial responsiveness to both cold dry air and histamine in presently symptom- and medication-free pediatric and adolescent asthma patients. SUBJECTS: Thirty-six children and adolescents with atopic asthma were studied. METHODS: On 2 consecutive days, bronchial responsiveness was assessed nonpharmacologically by cold dry air and pharmacologically by histamine in random order. Blood samples for determination of ECP were collected before each challenge. RESULTS: Serum ECP levels correlated with neither cold dry air-induced changes in FEV1 nor the provocation concentrations of histamine causing a 20% fall in FEV1. Subjects with bronchial hyperresponsiveness to cold dry air and histamine had somewhat higher levels of serum ECP than subjects with normal responses, but these differences were insignificant. CONCLUSIONS: Our results indicate a lack of relationship both between serum ECP and bronchial responsiveness to cold dry air and between serum ECP and bronchial responsiveness to histamine.