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.

A comparison of a single-step cold-dry air challenge and a routine histamine provocation for the assessment of bronchial responsiveness in children and adolescents.

BACKGROUND: It has remained unclear whether bronchial responsiveness as measured by a single-step cold-dry air challenge (CACh) correlates closely to the responsiveness that is assessed by a routine pharmacologic challenge. METHODS: On 2 consecutive days, we performed a CACh and a histamine challenge in 128 symptom- and medication-free pediatric and adolescent asthma patients. The CACh consisted of 4 min of isocapnic hyperventilation of -10 degrees C, absolutely dry air; responsiveness was expressed by the induced change in FEV1 (delta FEV1). The histamine challenge consisted of sequential inhalations of incremental increases in concentrations of histamine; responsiveness was expressed by the concentration which caused a 20% fall of FEV1 (PC20). RESULTS: Five children did not bronchoconstrict sufficiently in the histamine challenge for measuring a PC20 and were excluded from analysis. In the remaining 123, delta FEV1 (CACh) ranged from +5 to -73%, PC20 (histamine) from 0.05 to 7.2 mg/mL. There was a statistically significant correlation between delta FEV1 and PC20 (r = 0.54, p < 0.001), but also a considerable scatter of individual data points around the regression line. Fifty-two subjects were hyperresponsive by CACh and 114 by histamine criteria. CONCLUSIONS: There is a relatively weak correlation between the results of these two challenges; thus, one cannot be substituted one for the other. Histamine appears as more sensitive in detecting airway hyperresponsiveness than CACh. The poor correlation between the responses to these two challenges can be explained by differences between the challenge protocols, or, alternatively, by differences between applied stimuli and activated mechanisms.

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.

Airway obstruction and airway wall instability in cystic fibrosis: the isolated and combined effect of theophylline and sympathomimetics.

Multiple aspects of lung function were measured in 17 cystic fibrosis (CF) patients on four occasions: without therapy (0); with oral theophylline medication (Th); after inhalation of salbutamol (beta 2); and with combined medication (Th + beta 2). In addition to routine measurements, partial and maximum expiratory flow-volume (MEFV) curves were superimposed, and the flow transient equivalent of the MEFV curve was determined. Its volume dimension (volume of airway contribution, VACMEFV) partially reflects airway distensibility. Changes in airway compressibility--the other consequence of airway wall instability--were assessed by observing changes in end-expiratory flow rate. Airway resistance, expired volumes, and early expired flow rates, as well as VACMEFV improved significantly after beta 2 medication. Mean end-expiratory flow also increased after beta 2; in two patients, however, it decreased significantly, indicating that enhanced airway compression dominated over the release of bronchospasm. The alone had only minor effects on lung function. Early expired volume and flow rates as well as VACMEFV showed no significant difference between beta 2 alone and Th + beta 2; airway resistance even decreased significantly with this drug combination. End-expiratory flow rate, however, was significantly lower after Th + beta 2 than after beta 2 alone. Although theophylline does not alter lung function in most patients with CF, sympathomimetics relieve bronchospasm in many, but they enhance airway compressibility and thereby decrease peripheral expiratory airflow in some.(ABSTRACT TRUNCATED AT 250 WORDS)

Forced expirations against a variable resistance: a new chest physiotherapy method in cystic fibrosis.

Twenty patients with cystic fibrosis (CF) were trained to mobilize intrabronchial secretions by a new method of positive expiratory pressure mask (PEP mask) physiotherapy (PT). Patients repeatedly expired forcefully through the PEP mask; expiratory resistance was varied by eight different internal diameter resistors at the outlet. Forced vital capacity with the mask (FVCPEP) was determined for each resistor and was compared with the one measured without the instrument (FVC); simultaneously the sustained expiratory pressure (SEP) developed against the resistance was recorded. After training, each patient exceeded FVC with one or more resistors; "optimum" FVCPEP was 124 +/- 16% FVC at a SEP of 61 +/- 21 cm H2O. Using the PEP mask, patients cleared a higher percentage of their daily sputum volume than with conventional PT (78 +/- 22% versus 53 +/- 17%, p less than 0.01). In 11 patients (subgroup 1), multiple aspects of lung function were measured at the beginning of the study, after 10 months with PEP mask PT, after two further months without using the mask but with conventional PT, and after six more months with PEP mask PT. Results showed significantly increased expiratory flow rates, significantly decreased hyperinflation and airway instability with PEP mask PT, and a marked decline of lung function without it. The remaining nine patients (subgroup 2) entered into the same protocol; based on findings in subgroup 1 and on ethical considerations, however, the control period without PEP mask PT was then omitted, resulting in a steady and statistically significant improvement of lung function over the entire observation period. In the course of preliminary trials, two children transiently used a suboptimal resistance (FVCPEP less than FVC) and responded with a deterioration of lung function. By dilating airways and evacuating trapped gas, this method of PEP mask PT improves lung function and mucus clearance in CF. Thorough practice with the technique and frequent control of the optimal resistance are mandatory.

Cold air challenge of airway reactivity in children: a correlation of transcutaneously measured oxygen tension and conventional lung functions.

For pharmacological challenges, a correlation between the induced changes of the transcutaneously measured oxygen tension (PtcO2) and of conventional pulmonary function tests (PFTs) has been documented. We performed a 4-minute cold air challenge (CACh) in 17 children with bronchial asthma under continuous monitoring of PtcO2, and correlated observed changes with CACh-induced alterations of conventional PFTs. PtcO2 decreased significantly with CACh (from 86 +/- 10 mmHg to 66 +/- 14 mmHg, P less than 0.001), but returned to near-baseline within the next 30 minutes. PFTs changed with a similar pattern; the closest correlation was found between the CACh-induced fall of PtcO2 and Delta-FEV1 (r = 0.833, P less than 0.001). Changes of FVC, PEF, and Vmax50 correlated significantly as well. PtcO2 can complement or substitute for conventional PFTs in assessing the response to CACh in children.

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.

Management of severe congenital tracheobronchomalacia by continuous positive airway pressure and tidal breathing flow-volume loop analysis.

We report on a now 9-month-old infant with severe tracheobronchomalacia associated with campomelic dysplasia. The diagnosis of tracheobronchomalacia was suggested in the neonatal period by typical changes of the tidal breathing flow-volume loop and was confirmed by tracheobronchoscopy. Tidal breathing flow-volume loop analysis also allowed to titrate the optimal, continuous positive airway pressure for the respiratory management of the patient. Since bedside pulmonary function testing is noninvasive and rapid, it may reduce the need for frequent bronchoscopic evaluations in the management of patients with tracheobronchomalacia.

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.

Effect of sleep stages on measurements of passive respiratory mechanics in infants with bronchiolitis.

The measurement of passive respiratory mechanics by the single-breath occlusion technique is one of the more frequently used tests of infant lung function. Measurements are routinely done under chloral hydrate sedation, and a possible influence of sleep stages on these measurements has not been evaluated so far. We combined the assessment of passive respiratory mechanics with sleep stage monitoring in 44 infants and toddlers with mild to moderately severe bronchiolitis. In 31 infants, only nonrapid eye movement (NREM) sleep was recorded. In 13 patients who showed both NREM and rapid eye movement (REM) sleep, compliance of the respiratory system was significantly lower during REM than NREM sleep (73.2 +/- 19.7 vs. 81.2 +/- 21.3 mL/kPa, P = 0.0007), while resistance remained essentially unchanged. This finding was explained by an unchanged airway opening pressure in combination with a significantly decreased extrapolated volume. As tidal volume did not change from NREM to REM, this indicates reduced dynamic elevation of lung volume during REM sleep and thus supports previous observations of decreased lung volume in this sleep stage. From a practical perspective, these findings argue for the monitoring of sleep stage during measurements of passive respiratory mechanics, thereby increasing the complexity of these measurements significantly.

[Recurring croup. New clinical, pathophysiological and etiological aspects]. / Der rezidivierende Krupp. Neue klinische, pathophysiologische und ätiologische Aspekte.

Three consecutive studies were concerned with clinical, pathophysiologic, and immunologic aspects of recurrent croup. The first investigation demonstrated that recurrent croup is a distinct disease entity which shares many clinical features with asthma and should be distinguished from viral laryngotracheobronchitis. In the second study a high incidence of airway hyperreactivity was found in children with recurrent croup. This specific type of hyperreactivity suggested an involvement of both the lower and the upper respiratory tract. The third study demonstrated a tendency towards low serum IgA levels in children with recurrent croup; hence immunoregulatory defects may be conductive to the development of this disorder.

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.