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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.

Background and Objective: Allergic asthma is common in children, and house dust mite (HDM) is an important source of perennial allergens. Bronchial hyperresponsiveness is a functional hallmark of asthma. Specific immunotherapy (SIT) with HDM extracts were shown to decrease symptoms, but its effect on bronchial responsiveness, as measured by non-pharmacological challenges, has not been evaluated., Methods: Twenty-six paediatric asthma patients allergic to HDM participated in this study. Fourteen patients received SIT with a HDM extract (Alavac, Bencard) for 2 years, and 12 served as controls. Bronchial responsiveness was assessed non-pharmacologically by cold dry air challenge (CACh) before and 3, 6, 12 and 24 months after SIT, and 12 months after termination of SIT., Results: After 24 months, the SIT group showed a statistically significant reduction of the mean CACh-induced changes of both forced expiratory volume in one second (-21.8+/-2.7% vs. -13.7+/-2.4%; P = 0.03) and maximal expiratory flow at 25% remaining vital capacity (-48.9+/-4.9% vs. -27.9+/-6.2%; P = 0.01). In contrast, no significant changes of bronchial responsiveness were observed in the control group. In the SIT group more patients lost their bronchial hyperresponsiveness than in the control group (6/14 vs. 1/12; P<0.05). One year after terminating SIT, the treatment group showed a tendency towards returning bronchial hyperresponsiveness., Conclusion: These results demonstrate that during 2 years of SIT there was a reduction of bronchial hyperresponsiveness in HDM-allergic paediatric asthma patients.

In adolescence, some paediatric asthma patients will become symptom-free and require no further treatment. There is little information on the atopic status, lung function and bronchial responsiveness of these patients. Symptom-free asthma patients (n=118) aged 7.7-19.2 yrs, were evaluated 1 year after termination of therapy. Bronchial asthma had previously been diagnosed on the basis of recurrent wheezing episodes. Atopic status was assessed by skin-prick testing. Baseline lung function was measured by spirometry, flow-volume curve and plethysmography. Bronchial responsiveness was assessed nonpharmacologically by cold dry air challenge. Eighty one patients had at least one positive skin test result, and the remaining 37 were defined as nonatopic. In atopic subjects, the prevalence of bronchial hyperresponsiveness was significantly higher than in nonatopic patients (41 out of 81 versus 7 out of 37; p=0.001). Atopic subjects showed a significantly lower maximal expiratory flow at 25% remaining vital capacity (p<0.05) and a higher residual volume (p<0.05) than nonatopic subjects. Nonatopic subjects were significantly younger than atopic patients (p<0.01). These symptom- and medication-free paediatric and adolescent asthma patients could, thus, be divided into two groups: 1) atopic subjects with a tendency towards bronchial hyperresponsiveness; and 2) nonatopic subjects with better lung function and normal bronchial responsiveness In view of the increased understanding of the epidemiology of early childhood wheezing, these findings support the concept of different pathogenic mechanisms underlying wheezing episodes in early childhood.

Cold air challenge (CACh) can be applied by either a single step (SSCACh) or a multiple step (MSCACh) protocol. The interrelationship of the responses of the different protocols has not yet been studied. Furthermore, there is contradictory information on the correlation of cold air challenge responses to the outcome of pharmacological provocations. A single and a multiple step cold air challenge and a histamine provocation were performed in random order on three consecutive days on 28 children and adolescents with bronchial asthma, who were currently symptom- and medication-free. Single step cold air challenge consisted of a 4 min isocapnic hyperventilation of dry, -10 degrees C air; the subjects's response was quantified by the induced change in forced expiratory volume in one second (FEV1). Multiple step cold air challenge consisted of a series of 3 min, cold dry air hyperventilation steps from 20 to 80% of maximal voluntary ventilation (MVV); response was expressed as the provocative dose causing a 10% fall in FEV1 (PD10). Histamine provocation consisted of a series of 2 min inhalations of stepwise increasing histamine concentrations from 0.03 to 8.0 mg.mL-1; response was expressed as the provocative concentration of histamine causing a 20% fall in FEV1 (PC20). Change in FEV1 (delta FEV1) (SSCACh) correlated closely with PD10 (MSCACh); scatter around the regression line was minimal. With one exception, both types of CACh identified the same subjects as hyper- and normoresponsive. delta FEV1 (SSCACh) correlated significantly to PC20 (histamine), but scatter around the regression line was substantial. The correlation of PD10 (MSCACh) to PC20 (histamine) failed to reach statistical significance. These results indicate that the stimulus applied and the bronchoconstrictor mechanism activated, and not the challenge protocol, determine the outcome of a cold air challenge. In clinical practice, a brief single step cold air challenge can substitute for a more time-consuming multiple step cold air challenge. As nonpharmacological challenges seem to measure a different type of bronchial responsiveness, neither a single step nor a multiple step cold air challenge can substitute for a pharmacological provocation.

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.

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.

Cold air challenge (CACh) for measuring airway reactivity uses respiratory heat or water loss as a bronchoconstrictor stimulus; this stimulus is also important for the development of exercise-induced asthma, for which late asthmatic reactions (LARs) have been described. At 1200 hr on day 1, 22 children with asthma started to record their peak expiratory flow rate (PEFR) in 3 hr intervals until 0900 hr on day 2. At 1000 hr, they underwent a standardized 4 min CACh. Children then inhaled salbutamol and continued to record PEFR until 0900 hr on day 3. As a bronchodilator effect, PEFR measurements were significantly higher 2, 5, and 8 hr after CACh, but subsequently did not differ significantly from pre-CACh values. At 5 hr after CACh, individual values ranged from 95 to 137% of the corresponding pre-CACh measurements, at 8 hr from 94 to 150%, and at 11 hr from 80 to 121%. This random sample of children with asthma demonstrated no LAR after CACh.

Two girls with asthma died suddenly in autumn-winter 1985. On clinical criteria, both had been classified as moderately severe asthmatics, had shown a stabilised disease course, and had complied with antiasthmatic medication. By chance, lung function, bronchial reactivity, and subjective perception of lung function impairment had been assessed five and a half months and one month before death, respectively. For comparative purposes, we measured lung function and bronchial reactivity in a reference group of 37 children who had asthma of the same clinical severity and who were taking the same medication. In comparison with this reference group the index subjects showed a high degree of bronchial reactivity, incomplete recovery of function after bronchodilation, and appreciably reduced perception of severe lung function impairment. Regular assessment of lung function, bronchial reactivity, and perception of breathlessness might help to identify the patient who is prone to a fatal attack of asthma.