Evaluation of Bronchial Hyperresponsiveness by Monitoring of Transcutaneous Oxygen Tension and Arterial Oxygen Saturation during Methacholine Challenge in Asthmatic Children

Background. Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but the measurement of BHR is hampered by the fact that most tests of airway caliber are difficult to conduct at a young age. Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen pressure (tcPO₂) and pulse oximetry. Evaluating BHR by monitoring tcPO₂ instead of respiratory resistance (Rrs) has been used over a wide age range in childhood.

Objective. To investigate whether there is a consistent relationship between changes in arterial oxygen saturation (SaO₂) and respiratory resistance (Rrs) similar to the relationship between tcPO₂ and Rrs during methacholine challenge in young children and to assess the usefulness of SaO₂ as a parameter for the indirect measurement of BHR.

Method. We performed methacholine inhalation challenge by monitoring SaO₂, tcPO₂ and Rrs in 37 asthmatic children 5 to 7 years of age. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO₂ from the baseline was reached. We recorded the cumulative dose of methacholine (Dmin) at the inflection point of tcPO₂ (Dmin-tcPO₂), SaO₂ (Dmin-SaO₂), and Rrs(Dmin-Rrs).

Results. The mean value of Dmin-Rrs was 4.27 ± 2.02 units, the mean value of Dmin-tcPO₂ was 4.48 ± 2.01 units, and the mean value of Dmin-SaO₂ was 4.57 ± 0.20 units. Inhalation of increasing doses of methacholine raised Rrs curvilinearly and depressed tcPO₂ and SaO₂. There were no significant differences between any of the parameters. There were significant relationships between Dmin-tcPO₂ and Dmin-Rrs (r = 0.914, p < 0.001) and between Dmin-SaO₂ and Dmin-Rrs (r = 0.905, p < 0.001) and a relationship between Dmin-tcPO₂ and Dmin-SaO₂ (r = 0.949, p < 0.001).

Conclusion. We concluded that measurement of SaO₂ and/or tcPO₂ during methacholine inhalation challenge may be used to assess bronchial hyperresponsiveness. This study showed that both SaO₂ and tcPO₂ monitoring are safe, useful, and tolerable for use in children who are too young to cooperate with lung function tests.     

Effect of aging on the relationship between asthma severity and bronchial hyperresponsiveness in children with asthma.

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma. We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys:girls = 193:130, mean age 9.7 years) and 63 age-matched controls (boys:girls = 25:38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO2) in children less than 6 years of age (Dmin-PO2) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO2 and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2-5 years, the Dmin-PO2 levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO2 levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6-9 years and 10-13 years. In the asthmatics aged 14-20 years, the Dmin-Rrs levels were not significantly different among the three groups. Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.     

Effect of Aging on the Relationship between Asthma Severity and Bronchial Hyperresponsiveness in Children with Asthma

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma.

We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys : girls = 193 : 130, mean age 9.7 years) and 63 age-matched controls (boys : girls = 25 : 38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO₂) in children less than 6 years of age (Dmin-PO₂) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO₂ and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2–5 years, the Dmin-PO₂ levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO₂ levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6–9 years and 10–13 years. In the asthmatics aged 14–20 years, the Dmin-Rrs levels were not significantly different among the three groups.

Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.     

Relationship between bronchial hyperresponsiveness and development of asthma in wheezy infants

STUDY OBJECTIVES: To evaluate the relationship between bronchial hyperresponsiveness (BHR) in infants with wheezing and the subsequent development of asthma. INTERVENTION: Bronchial reactivity to inhaled methacholine (BRm) during the infantile period was studied using the transcutaneous partial pressure of oxygen (tcPO(2)) method. Children were followed long-term for the development of asthma. PATIENTS: Fourteen children with bronchiolitis (mean age, 0.7 years) and 48 with wheezy bronchitis (mean age, 2.3 years) were enrolled. For comparison, 40 children with asthma (mean age, 4.6 years) and 27 healthy control subjects without chronic respiratory disease (mean age, 2.7 years) were studied. MEASUREMENTS: Consecutive doses of methacholine were doubled until a 10% decrease in tcPO(2) from baseline was reached. The cumulative dose of methacholine (Dmin) at the inflection point of tcPO(2) (Dmin-PO(2)) was recorded. RESULTS: During > 10 years of follow-up, seven patients with bronchiolitis developed asthma and all patients in the higher BRm set developed asthma, compared with none in the lower BRm set. In the wheezy bronchitis group, Dmin-PO(2) values in the 32 patients who developed asthma were lower than those in patients who had not developed asthma (p < 0.001). CONCLUSIONS: We concluded that there is a tendency for infants with a clinical diagnosis of bronchiolitis or wheezy bronchitis and who show BHR in the infantile period to develop asthma. The presence of increased BHR after infantile respiratory diseases associated with wheezing may be a prelude to the development of childhood asthma.     

Bronchial hyperresponsiveness in children with atopic and nonatopic asthma

We have studied the bronchial hyperresponsiveness of children with atopic and nonatopic asthma by methacholine inhalation challenge, using a new device, the "Astograph." Three parameters, initial respiratory resistance (Rrs cont), bronchial sensitivity (Dmin), and bronchial reactivity (St), were studied. The Rrs cont values of atopic asthma were higher than those of the disease controls (p less than 0.05), while there was no difference between nonatopic asthma and disease controls. The Dmin values of atopic and nonatopic asthma were lower than those of disease controls (p less than 0.001; p less than 0.01). The St values of atopic and nonatopic asthma were higher than those of disease controls (p less than 0.001; p less than 0.01). There was no difference of Rrs cont and Dmin between the children with atopic and nonatopic asthma. However, St of the children with nonatopic asthma was remarkably higher than that of the children with atopic asthma (p less than 0.001). These data suggested that there was a remarkable difference of bronchial response to methacholine between the children with atopic asthma and those with nonatopic asthma.     

Validation of a single concentration methacholine inhalation provocation test (SCIPT) in children.

A new method to assess bronchial hyperresponsiveness (BHR) using a single concentration methacholine has already been validated in adults with asthma. Because the geometrical dimensions of the airways in children are different, the results from studies in adults cannot be extrapolated to children. In this study, we validated the single concentration methacholine inhalation provocation test (SCIPT) in children. Twenty-two children performed three methacholine inhalation challenge tests in random order. Two challenges were performed according to the SCIPT: doubling doses (0.03-1.8 mg; maximal cumulated dose 3.6 mg) were administered with an Aerosol Provocation System (Masterscope, Jaeger). The third challenge was performed according to a standard dosimeter method (SDM): doubling doses (0.002-1.8 mg; maximal cumulative dose 3.5 mg) were administered with a DeVillbiss 646 nebulizer. The degree of BHR is expressed as a PD20. A difference of < 1.5 dose step was assumed to be due to intraindividual variation. We found an intraclass correlation of 0.91 between both tests according to the SCIPT and of 0.80 between the SCIPT and SDM. We found, according to the method of Bland and Altman, good agreement when comparing these two challenge tests. The single concentration inhalation provocation test is reproducible and shows good agreement with a standard dosimeter method to test bronchial responsiveness in children.     

气道组胺H2受体与支气管哮喘发病机理关系的临床研究

应用组胺Ｈ２受体（Ｈ２Ｒ）激动剂甲双咪胍治疗缓解期哮喘患者１９例，观察其对气道高反应性（ＢＨＲ）的作用，以进一步探讨Ｈ２Ｒ与哮喘发病机理的关系。研究提示Ｈ２Ｒ激动剂可主要作为抗气道炎症用药，也可作为平喘药的辅助用药，说明Ｈ２Ｒ在哮喘气道炎症反应中具有保护作用。     

Effect of age,height, and prechallenge respiratory resistance on bronchial hyperresponsiveness in childhood asthma using the forced oscillation technique

To evaluate the effects of age, height and prechallenge respiratory system resistance (Rrs) on bronchial responsiveness to methacholine inhalation (BRm) as measured by the oscillation technique in children with mild asthma, we studied BRm in 92 atopic children aged from 8 to 13 years (mean ± SD, 10.5 ± 1.7 years). Inhalation challenge was performed by administering progressively doubling doses of methacholine, until a twofold increase in Rrs from baseline had been reached. The minimum cumulative dose of methacholine (Dmin) at which Rrs deviated from baseline was identified by the point of deflection of the continuously recorded Rrs tracing. The Dmin represented the amount of methacholine which elicited BRm. By using single-regression analysis, height was negatively correlated with Rrs (p < 0.001). Height was positively and Rrs was negatively correlated with age (p < 0.001 and p < 0.001, respectively). Furthermore, height and age were correlated with Dmin (p < 0.001 and p < 0.001, respectively), but prechallenge Rrs was not correlated with Dmin (p > 0.1). To minimize the effect of height and prechallenge Rrs on BRm, the relationships between Dmin and age was studied in a subgroup with a narrow range of heights (135–155 cm, n = 32), and a narrow range of prechallenge Rrs (5.0–6.9 cmH₂ O/L/s, n = 42); there remained a statistically significant correlation between Dmin and age in the groups with comparable heights (p = 0.026) and Rrs (p = 0.003). These data suggest that the BHR in childhood asthma may be affected by height and age when measured by the oscillation technique. Considering the many advantages of the oscillation method, this technique may be very suitable for measuring BHR in childhood asthma. Pediatr Pulmonol. 1996;22:1–6. © 1996 Wiley-Liss, Inc.     

Difference in airway reactivity in children with atopic vs nonatopic asthma.

STUDY OBJECTIVE: To examine the difference in the mechanisms of bronchial hyperresponsiveness (BHR) in nonatopic asthma and in atopic asthma, we studied bronchial reactivity against nonspecific stimuli in children with atopic asthma and nonatopic asthma. DESIGN AND PARTICIPANTS: Fourteen children with nonatopic asthma, 24 children with atopic asthma, and 20 age-matched controls participated in this study. MEASUREMENTS: Inhalation challenge was performed by administering progressively doubling doses of methacholine with a continuous inhalation provocation method. The speed of bronchoconstriction to methacholine (Sm) and the speed of reversal of bronchoconstriction to methacholine after inhalation of a beta2-agonist (r-Sm), which was considered to represent the effect of the beta2-agonist, were calculated from the dose-response curve. RESULTS: The value of Sm was higher in the nonatopic asthma group than in the atopic asthma group and the control group. The value of r-Sm was also higher in the nonatopic asthma group than in the atopic asthma group, but did not differ from that in the control group. CONCLUSION: These results indicate that bronchial reactivity against methacholine and the beta2-agonist was greater in nonatopic asthma than in atopic asthma, and that the mechanism of BHR in children with nonatopic asthma may differ from that in children with atopic asthma.     

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.     

Relationship between bronchial hyperresponsiveness and development of asthma in children with chronic cough

To evaluate the relationship between bronchial hyperresponsiveness (BHR) and the development of asthma in children with chronic cough, we performed methacholine inhalation challenges and transcutaneous oxygen pressure (tcPO2) measurements in 92 children with chronic cough aged from 1-13 years (55 boys and 37 girls; mean, 5.3 years) and followed them for > or = 10 years. Forty-four age-matched children with asthma (24 males and 20 females; mean, 6.5 years) and 44 age-matched children without cough or asthma served as controls (18 males and 26 females; mean, 4.6 years). Consecutive doubling doses of methacholine were inhaled until a 10% decrease in tcPO2 from baseline was observed. The cumulative dose of methacholine at the inflection point of the tcPO2 record (Dmin-PO2) was considered to represent hyperresponsiveness to inhaled methacholine. After 10 years or more of follow-up, 60 of the 92 subjects with cough answered our questionnaire, and 27/60 had been diagnosed with asthma. There was a statistical difference in Dmin-PO2 between the children who presented with chronic cough originally and who developed asthma (asthma-developed group) and those who did not develop asthma (asthma-free group). There was no difference in the value of Dmin-PO2 between the asthma-developed group and the asthma group, or between the asthma-free group and the age-matched control group. Among the children with chronic cough, there was no difference in Dmin-PO2 between girls and boys, either in the asthma-developed group or in the asthma-group. We conclude that 45% of the children with a chronic cough in early life developed asthma, and that BHR in children with chronic cough during the childhood period is a strong risk factor for the development of asthma.     

Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV(1) between patients with asymptomatic bronchial hyperresponsiveness and mild asthma

BACKGROUND: A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. RESULTS: There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.     

Extrathoracic airway responsiveness in children with asthma-like symptoms,including chronic persistent cough

Asthma-like symptoms, including chronic persistent cough, are not always specific for classical asthma. In order to investigate whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped in the evaluation of pediatric patients with asthma-like symptoms such as chronic cough, we examined 133 consecutive, unselected patients (mean age, 10.06 +/- 2.16 years) who had neither established asthma nor bronchial obstruction previously. We recorded the forced mid-inspiratory flow (FIF(50)) as an index of extrathoracic airway narrowing. In addition, a 25% decrease in FIF(50) (PD(25)FIF(50)) below the cutoff concentration of < or = 8 mg/mL methacholine was assumed to indicate EAHR. According to the methacholine response, 81 patients had EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR); 39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13 patients and not in any of the control children. When patients with cough as the sole presenting symptom (60.9%) were compared with those with cough and wheeze (20.3%), those with cough alone had a significantly greater probability of having EAHR (OR, 4.16; 95% CI, 1.32-13.13) and a lower probability of having BHR (OR, 0.70; CI, 0.25-1.95) than those with cough and wheeze. Patients with cough, wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than those with cough alone (OR, 5.08; CI, 1.55-16.64). Patients with cough and wheeze as compared with those with cough, wheeze, and dyspnea had significantly greater probability of having both EAHR and BHR (OR, 4.71; CI, 1.94-11.47).In order to ascertain the clinical relevance of EAHR, we assessed in the second part of the study whether the effects of treatment of the underlying disease would result in relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR. They received specific therapy for their upper airway diseases for 4 weeks. Compared with values before treatment, FIF(50) and forced expiratory volume in 1 sec (FEV(1)) did not change significantly. The dose of methacholine causing a 20% fall in FEV(1) (PD(20)FEV(1)) and PD(25)FIF(50) values were significantly increased from 2.40 +/- 1.39 to 4.22 +/- 1.13 mg /mL (P < 0.001) and from 1.03 +/- 1.75 to 8.71 +/- 1.21 mg /mL (P < 0.0001), respectively.We conclude that measurements of EAHR and BHR are the most important ways to evaluate children with asthma-like symptoms, including chronic persistent cough when chest X-rays and pulmonary function tests remain within normal limits. Therefore, empirical treatment is not necessary when these investigations are available. Our results suggest that specific treatment of inflammation in the upper airways reversed persistant cough, and may play an important role in modulating lower airways responsiveness in patients with concomitant BHR.     

Dissimilarity in methacholine and adenosine 5'-monophosphate responsiveness 3 and 24 h after allergen challenge

Bronchial hyperresponsiveness (BHR) to methacholine and adenosine 5'-monophosphate (AMP) was studied in 15 allergic asthmatic patients before and 3 and 24 h after allergen challenge with house dust mite (HDM). Subjects attended the clinic on 3 consecutive days. On the first day a control solution was inhaled, and methacholine or AMP challenge was performed 3 h later. The next day HDM was inhaled, and 3 and 24 h later methacholine or AMP challenge was performed again. There were no significant difference in FEV1 baseline value between any of the study days. PD20 HDM, percentage decrease in FEV1, and AUC for both the EAR and LAR were not significantly different in the methacholine and AMP studies. After HDM challenge, PC20 methacholine decreased significantly from a geometric mean (+/- SEM) starting value of 1.39 +/- 0.63 mg/ml to 0.30 +/- 0.78 mg/ml (p less than 0.001) at 3 h and to 0.22 +/- 0.75 mg/ml (p less than 0.001) at 24 h. The magnitude of the decrease in PC20 methacholine at 3 h correlated with the severity of the late asthmatic reaction (LAR) as measured by the percentage fall in FEV1 and area under the curve (AUC) (r = -0.60 and r = 0.55; p less than 0.05). A significant decrease was observed in the PC20 AMP at 3 h, from a geometric mean value of 12.2 +/- 0.96 mg/ml after challenge with the control solution to 4.47 +/- 0.99 mg/ml (p less than 0.05) after HDM challenge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atopic status and level of bronchial responsiveness in parents of children with acute bronchiolitis.

To examine whether children with a genetic predisposition to asthma are more likely to be afflicted with bronchiolitis, we studied 122 parents of infants who were hospitalized with the diagnosis of acute bronchiolitis (index group) and 120 parents of children who had never suffered from this disease (control group). The parents underwent bronchial challenge testing with methacholine and skin prick testing with common airborne allergens, and gave blood specimens for measurement of serum total IgE. There was no difference in atopic status, as assessed by the prevalence of atopy (at least one positive response to the allergens tested) or by serum total IgE levels, between index and control parents. The prevalence of bronchial hyperresponsiveness (BHR) (concentration of methacholine causing a 20% reduction in forced expiratory volume in 1 sec [PC20] < 18 mg/mL) was higher in index parents than in control parents (17.2% vs. 7.5%, p = 0.02). Bronchial responsiveness (BR) index was significantly higher in index parents than in control parents (1.135 +/- 0.088 vs. 1.104 +/- 0.071, p < 0.01). Parents of children who were hospitalized with acute bronchiolitis showed a higher level of BR, but not atopy. This suggests that in terms of BHR, there may be a genetic predisposition to the development of bronchiolitis.     

Methacholine-induced volume dependence of respiratory resistance in preschool children.

Enhanced negative volume dependence of airway resistance is associated with bronchoconstriction in tracheostomized paralysed open-chest animals. Significant upper airways responses may be associated with bronchoconstriction and could thereby alter the pattern of volume dependence in spontaneously breathing subjects. The aim of the study was to test whether volume dependence of respiratory resistance (Rrs) could be demonstrated in preschool children undergoing routine methacholine challenge. The volume dependence of respiratory oscillation resistance at 12 and 20 Hz (Rrs,12 and Rrs,20) was examined in eight 4-5.5-yr-old children showing a positive response to methacholine. Multiple linear regression analysis was also used to account for flow dependence during tidal breathing (Rrs,12 or Rrs,20=K1+K2?V'?+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p<0.01). For instance, the mean+/-SD inspiratory K3 at 20 Hz was 4.1+/-1.3 hPa x s x L(-2) at baseline and -15.0+/-4.3 hPa x s x L(-2) after methacholine, in which case it was also larger on expiration than on inspiration (p<0.05), possibly as a result of upper airway responses. A significant increase in the negative volume dependence of respiratory resistance may thus be shown in preschool children in response to methacholine. The volume dependence (K3) during inspiration may be particularly useful in detecting bronchoconstriction, because it is less likely to be affected by upper airway mechanisms than during expiration.     

Methacholine challenge in preschool children: methacholine-induced wheeze versus transcutaneous oximetry.

Tracheal/chest auscultation for wheeze and transcutaneous oximetry have both been suggested as measures of outcome in bronchial provocation tests in young children. This study aimed to compare the sensitivity and safety of these two techniques as end-points for methacholine challenge in children aged <4 yrs. Seventy-two methacholine challenges were performed in 39 children aged <4 yrs with recurrent wheeze. Arterial oxygen saturation (Sa,O2) and transcutaneous oxygen pressure tcPO2 continuously, and the test was terminated when wheeze was heard or at Sa,O2 <91%. tcPO2 was not used as an end-point. Wheeze or desaturation occurred at < or =8 mg x mL(-1) methacholine in every test. One child had transient clinical cyanosis, but no other ill-effects were seen. Fifty-six tests (78%) were terminated for wheeze, seven (10%) for fall in Sa,O2 and nine (12%) showed simultaneous responses in both parameters. Twenty-eight tests (39%) contained a fall in tcPO2 >3 kPa but six of these also showed a significant rise. Fifty-three tests (75%) contained a fall in tcPO2 >15%, but 20 of these also showed a significant rise. Tracheal/chest auscultation with Sa,O2 monitoring is a sensitive and relatively safe end-point for bronchial challenges in preschool children. The erratic pattern of transcutaneous oxygen pressure response in some children casts doubt on its reliability as a proxy measure of bronchial obstruction.     

Safety and Tolerability of Methacholine Challenge in Infants with Recurrent Wheeze

Bronchial hyperreactivity (BHR) is a key feature of asthma, but measurement can usually not be achieved in infants with standard lung function tests. We investigated the safety and tolerability of methacholine challenge in infants with recurrent wheezing episodes. 78 methacholine challenges in 51 sedated infants aged 12–36 months with recurrent wheezing episodes were performed. Methacholine challenge was stopped when clinical signs (coughing, wheezing, or cyanosis) or a drop of oxygen saturation (SPO2) of at least 5% or a drop of transcutaneous oxygen tension (P_tcO2) of at least 0.8 kPa or an increase of resistance (R_rsSO), of 50% by single occlusion technique were observed. Prior to methacholine challenge, all children were symptom-free with a mean SPO2 of 97.4% (SD 1.80%). In 48 cases (61.5%), no clinical sign was observed, 17 (21.8%) coughed, and 13 (16.7%) wheezed. A mean reduction of SPO2 of 5.0% (SD 3.89%) for the entire population was observed. In 15 of 78 cases, a decrease of SPO2 <90% occurred. This SPO2 drop was short-lasting and resolved spontaneously or after bronchodilator inhalation. Infants whose SPO2 dropped <90% showed a greater increase of R_rsSO compared to infants who did not drop <90% (133% vs. 65% R_rsSO increase, p<0.001). Methacholine challenge, using a combination of clinical observation, monitoring of SPO2 and P_tcO2, and airway resistance using the single-occlusion technique, is a safe and tolerable tool to measure the BHR in infants with recurrent wheezing episodes.     

Transcutaneous oxygen tension measurements during methacholine challenge of prematurity in infants with chronic lung disease

Chronic lung disease (CLD) of prematurity may be caused by a number of insults during mechanical ventilation, including barotrauma and hyperoxia. To evaluate bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we measured changes in transcutaneous oxygen tensions (tcPO₂) during methacholine inhalation challenge. Twelve infants with CLD and 22 age-matched children without respiratory diseases were enrolled in this study (ages—5 to 36 months; mean age—16.2 months). Serial doses of methacholine were doubled until a 10% decrease in tcPO₂ from baseline was reached. The cumulative dose of methacholine inhaled by the time tcPO₂ had been reached (Dmin-PO₂) was considered to represent the dose at which reactivity to methacholine (RO₂meth) had occurred. In the CLD group, Dmin-PO₂ (3.50 ± 0.1 log.milli-units) was significantly lower than in the preterm control infant group (4.31 ± 0.2 log·milli-units) and the term infant group (4.21 ± 0.1 log.milli-units) (P = 0.004, P < 0.001). Dmin-PO₂ in the preterm control infant group was not significantly different than in the term infant group (P > 0.5). These results suggest that infants who require additional therapeutic oxygen and mechanical ventilation during the early months of life are at risk of developing early-onset, long-lasting respiratory disease that is related to an acquired BHR. Pediatr Pulmonol. 1998; 25:338–342. © 1998 Wiley-Liss, Inc.     

Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1)

Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia (> or =275/mm(3)), and BHR to methacholine and AMP (> or =15% fall in FEV(1)). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose-response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% CI: 1.22;5.17), allergic asthma (PR 4.38, 95% CI: 1.98;9.66), with atopy (PR 3.87, 95% CI: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% CI: 1.48;8.77), but not with baseline FEV(1). BHR to methacholine was inversely related to prechallenge FEV(1) (PR 0.97, 95% CI: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic-allergic rhinitis-allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.