Hyperreactivity In Children Research Articles

The Effects of Inhaled Fluticasone and Pranlukast on Bronchial Hyperreactivity in Children with Asthma

Background: Guidelines recommend inhaled corticosteroids and leukotriene modifiers as daily therapies to control asthma in children. However, few studies have compared the effects of these drugs on bronchial hyperreactivity in children with asthma.Methods: The effects of inhaled fluticasone and pranlukast on bronchial hyperreactivity in 42 patients aged 7–15 years with mild persistent asthma (24 treated with inhaled fluticasone and 18 with pranlukast), who had experienced no asthma exacerbations after these treatments started, were studied. At the start of and after 6 and 18 months of treatment, bronchial hyperreactivity (PC20: provocative concentration of methacholine causing a 20% fall in FEV1) was assessed with methacholine.Results: Geometric averages of PC20 in patients treated with inhaled fluticasone were 385.2 μg/mL at the start, 2271.8 μg/mL after 6 months, and 4181.0 μg/mL after 18 months of treatment, whereas those patients treated with pranlukast were 415.8 μg/mL, 792.2 μg/mL, and 2105.1 μg/mL,...

Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study

Sublingual immunotherapy (SLIT) has been proved to be effective in allergic rhinitis and asthma, but there are few data on its preventive effects, especially in children. To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations, clinical symptoms, and bronchial hyperreactivity. A total of 216 children with allergic rhinitis, with or without intermittent asthma, were evaluated and then randomized to receive drugs alone or drugs plus SLIT openly for 3 years. The clinical score was assessed yearly during allergen exposure. Pulmonary function testing, methacholine challenge, and skin prick testing were performed at the beginning and end of the study. One hundred forty-four children received SLIT and 72 received drugs only. Dropouts were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95% confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year. The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group. Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported systemic itching. In everyday clinical practice, SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy.

Increased Leukotriene E4 in the Exhaled Breath Condensate of Children With Mild Asthma

Chronic airway inflammation is a feature of asthma. Increased levels of cysteinyl leukotrienes (cys-LTs; leukotriene [LT]C(4), LTD(4), LTE(4)) have been shown in the exhaled breath condensate (EBC) of children with moderate-to-severe asthma. The aim of this study was to examine the relationship between EBC cys-LTs (LTE(4)) levels and bronchial hyperreactivity in children with mild asthma in order to evaluate the clinical utility of measuring EBC cys-LTs levels. We measured LTE(4) levels in the EBC of children aged 8 to 18 years, including healthy nonasthmatic children (n = 6) and children with mild asthma (n = 37). Patients with mild asthma were classified into the following three groups: group 1, participants who had been asymptomatic (no wheezing/symptoms of asthma) for > 6 months prior to examination (n = 12); group 2, participants who were asymptomatic but had had wheezing/symptoms of asthma within 6 months before examination (n = 18); and group 3, patients with current wheeze and/or mild symptoms of asthma exacerbation at the time of examination. Exhaled LTE(4) levels were increased in all children with mild asthma compared with nonasthmatic control subjects (5.69 +/- 9.62 pg/20 min vs 0.74 +/- 0.79 pg/20 min, p < 0.05) [mean +/- SD]. In particular, the EBC LTE(4) levels in group 2 (4.99 +/- 6.70 pg/20 min) and group 3 (14.66 +/- 17.11 pg/20 min) were increased compared with control subjects and group 1 (1.50 +/- 1.69 pg/20 min). The EBC LTE(4) levels negatively correlated with the provocative concentration of methacholine causing a 15% fall in FEV(1) (r = - 0.454, p = 0.012). EBC cys-LTs may be useful as a noninvasive marker assessing airway inflammation and hyperreactivity in children with asthma.

Exercise, methacholine, and adenosine 5?-monophosphate challenges in children with asthma: Relation to severity of the disease

Bronchial hyperreactivity is a characteristic feature of asthma and can be evaluated by different challenges. The aim of this study was to compare exercise, methacholine (MCH), and adenosine 5'-monophosphate (AMP) challenges in 135 children and young adults (mean age +/- SD, 12.4+/-3.9 years) with asthma, and to examine the utility of the different challenges in predicting those children with asthma likely to require prophylactic antiinflammatory treatment. The sensitivity of MCH challenge in detecting bronchial hyperreactivity (at or below 8 mg/mL) was 98%, that of AMP challenge (at or below 200 mg/mL) 95.5%, and that of exercise (more than 8.2% fall in FEV(1)) was 65%. There was a significant difference between mild asthmatic children (85 patients, intermittent asthma, step 1 of NIH guidelines) and moderate asthmatics (50 patients, steps 2 and 3 of guidelines) in relation to the logarithmic mean provocation concentration to elicit a 20% fall in FEV(1) (PC(20)) to MCH (0.49 mg/mL vs. 0.15 mg/mL, P<0.00001), that to AMP (7.67 mg/mL vs. 3.60 mg/mL, P = 0.001), and in relation to the mean percent fall in FEV(1) after exercise (13.9% vs. 22.0%, P = 0.001). Sensitivity and specificity curves between the two severity groups of asthma were constructed, and the intersection point of the two curves for each type of challenge was determined. When mild asthmatics were compared to moderate asthmatics, the intersection points for MCH, AMP, and exercise were 66%, 63%, and 61%, respectively. Logistic regression analysis and receiver operating characteristic (ROC) curves of the three challenges for the two severity groups of asthma showed that methacholine was a better discriminating challenge between the severity groups than the other two challenges. We conclude that the sensitivities of AMP and MCH challenges in the detection of bronchial hyperreactivity in children and young adults with asthma are very similar and higher than that of exercise. There is a significant difference between mild and moderate asthmatics within the three bronchial challenges, with MCH discriminating better than AMP or exercise between groups.

Airway hyperreactivity in children with sickle cell disease

Progressive restrictive defect with increasing age, obstructive lung disease, and bronchodilator responsiveness have been reported in sickle cell disease (SCD). Because airway hyperreactivity (AHR) can be underestimated when assessed by bronchodilator responsiveness in patients with normal baseline lung function, the aim of this study was to investigate the prevalence of AHR in SCD by cold-air bronchial provocation testing, and to assess whether AHR can be present in symptom-free patients with SCD. Forty patients aged 6 to 19 years (mean, 10.7 years ± 3.5 SD) performed pulmonary function tests. Eighteen were known to have a history of reactive airway disease (RAD group), and 22 had no known history of RAD (non-RAD group). A control group, aged 6 to 17 years (mean, 10.5 ± 3.1 years), consisted of 10 siblings of the non-RAD SCD group. There were no significant differences in age and height among the groups. If the forced expiratory volume in 1 second (FEV 1 ) was greater than 70%, cold air challenge (CACh) was performed; if the FEV 1 was less than 70%, aerosolized bronchodilator therapy was given. A decrease in FEV 1 of more than 10% after CACh or an increase in FEV 1 of 12% or greater after bronchodilator inhalation was considered evidence of AHR. In the RAD group, the total lung capacity was 88.9% ± 14.0% of race-corrected predicted values, the forced vital capacity was 91.2% ± 12.6%, and FEV 1 was 85.3% ± 16.2%. The mean maximal percent fall in FEV 1 after CACh ( n = 13) was 18.5% ± 9.6% and was greater than 10% in 11 of 13 patients. The mean increase in FEV 1 after bronchodilator therapy ( n = 5) was 11.5% ± 8.3%, and it was greater than 12% in 4 of 5 patients. In the non-RAD group the baseline total lung capacity was 101.6% ± 11.7%, forced vital capacity was 95.5% ± 10.2%, and FEV 1 was 93.3% ± 13.2%. The mean maximal percent fall in FEV 1 after CACh ( n = 19) was 14.1% ± 8.8% and was greater than 10% in 13 of 19 patients. The mean increase in FEV 1 after bronchodilator therapy ( n = 3) was 14.7% ± 11.3%, and was 12% or greater in 1 of 3 patients. In the control group the baseline total lung capacity was 105.7% ± 12.1%, forced vital capacity was 96.2% ± 11.1%, and FEV 1 was 92.9% ± 10.3%. The mean maximal percent fall in FEV 1 was 5.0% ± 2.5%, and was greater than 10% in none of 10 patients. The prevalence of AHR in the control group, the RAD group, and the non-RAD group was zero, 83%, and 64%, respectively ( p < 0.0001). The overall prevalence in the SCD group was 73%. We conclude that there is a high prevalence of AHR in children with SCD and that airway hyperreactivity may exist in patients with SCD even in the absence of the clinical symptoms of RAD. AHR may be a significant component of sickle cell lung disease. (J Pediatr 1997;131:278-83 )

Methacholine Challenge in Detecting Bronchial Hyperreactivity in Children

Background The diagnosis of bronchial asthma is usually apparent from presenting signs and symptoms. Occasionally, however, there is uncertainty and clinicians may use bronchial hyperreactivity, determined by methacholine inhalation challenge, as a diagnostic aid. Children are known to be more sensitive to methacholine than adults; doses used in adults will result in false-positive responses. Objective To determine the optimal methacholine inhalation challenge dose providing sensitive and specific discrimination between bronchial hyperreactivity and normal reactivity in children. A second objective was to determine whether gender, baseline spirometry values, race, tobacco smoke exposure, and family income affect methacholine response. Method In 71 children aged 7 to 15 years airway hyperreactivity was determined by history and physical findings. Methacholine challenge was performed using an established protocol. Sensitivity and specificity of the challenge were calculated at 50, 100, and 225 breath units ...

Bronchial Hyperreactivity in Children With Sickle Cell Thalassemia

Background: Pulmonary damage and frequent infections are common in children with thalassemia or sickle-cell disease, an inherited disorder of hemoglobin structure. Objective: Although bronchial hyperreactivity is widely used in the assessment of other pulmonary diseases, such as asthma, it has not previously been studied in relation to sickle-cell disease. Methods: We investigated the bronchial response to a methacholine inhalation test in a group of 23 children with compound heterozygous sickle-cell disease (βsβ+th/βsβoth), comparing these results with reference data from a group of normal children, obtained in an earlier control study. Asthmatic patients were excluded on the basis of diagnostic history, past and present therapies, clinical assessment, and evidence of basal FEV1 less than 80% of that predicted for the age (range 6-12 years). Increasing doses of methacholine were inhaled at 2-min intervals, allowing a cumulative dose range of 30–2490 μg and measuring FEV1 after each inhalation in order to...

025-PA11 Passive smoking as a determinant of bronchial hyperreactivity in children with respiratory diseases

025-PA11 Passive smoking as a determinant of bronchial hyperreactivity in children with respiratory diseases

Blood eosinophils, eosinophil-derived proteins, and leukotriene C4 generation in relation to bronchial hyperreactivity in children with atopic dermatitis.

To assess the relation among eosinophil-related variables in the peripheral blood, bronchial hyperreactivity, and the presence of atopic dermatitis in children aged 5-14 years, we studied 11 patients with atopic dermatitis alone, six with asthma and atopic dermatitis, 12 with asthma alone, and 12 healthy controls. Eosinophil counts, levels of eosinophil cationic protein, and the capacity of eosinophils to generate leukotriene (LT) C4, as well as bronchial hyperreactivity and a severity score for atopic dermatitis, were determined. Eosinophil variables were significantly higher in both patient groups with atopic dermatitis than in normal controls. In particular, ionophore A 23187 LTC4 generation was higher in patients with atopic dermatitis alone (median 82, range 25-273 ng/10(6) cells) and patients with combined asthma and atopic dermatitis (median 68, range 32-583 ng/10(6) cells) than in normal controls (median 9, range 1-67 ng/10(6) cells). However, there was no difference between the group of atopic dermatitis patients with asthma and without asthma. We conclude that eosinophil variables in the peripheral blood are mainly influenced by the presence of atopic dermatitis, and not the presence and the severity of asthma in patients with both asthma and atopic dermatitis.

Bronchial Asthma and Hyperreactivity After Early Childhood Bronchiolitis or Pneumonia

To determine the infantile risk factors and long-term outcome up to 8 to 10 years of age for bronchial asthma and hyperreactivity in children with early-childhood bronchiolitis or pneumonia. Prospective follow-up of three groups of children. University hospital providing primary hospital care and outpatient consultations for all pediatric patients in a defined area. None. The study groups consisted of 62 children with early-childhood bronchiolitis, 29 children with early-childhood pneumonia with no wheezing, and 52 control children. Infantile risk factors were prospectively registered until 2 years of age. Clinical examination, performed 7 to 8 years later, included recording of atopic and asthmatic symptoms from the preceding 12 months. The methacholine inhalation challenge test was used to assess bronchial hyperreactivity, and mean midexpiratory flow results were used to assess bronchial obstruction. Bronchial asthma was present in nine (15%) of the 62 children from the bronchiolitis group, compared with 7% in the pneumonia group and 2% in the control group. Bronchial hyperreactivity indicated by methacholine inhalation challenge was far more common; it was present in 62% of the bronchiolitis group and in 45% of the pneumonia group. Both groups differed significantly from the control group. Decreased mean midexpiratory flow values were observed in 29% and 21% of the bronchiolitis and pneumonia groups, respectively. All 10 asthmatic patients had bronchial hyperreactivity, but only 20% of hyperreactive children had asthma. An analysis of infantile risk factors disclosed only one, an early onset of wheezing, with a significant effect on bronchial hyperreactivity at school age. Elevated IgE values measured during infancy were associated with the development of clinical asthma. The risk of bronchial asthma was increased after infantile bronchiolitis. Moreover, bronchial hyperreactivity was increased after both infantile bronchiolitis and pneumonia. Methacholine inhalation challenge was a sensitive but nonspecific test for diagnosing bronchial asthma. Both bronchiolitis and pneumonia resulting in hospitalization in early childhood distinguish a group of children with an increased risk for long-term lung function abnormalities and pulmonary illnesses.

Reproducibility of late phase pulmonary response to exercise and its relationship to bronchial hyperreactivity in children with chronic asthma.

To determine the reproducibility of the delayed response to exercise and its effect on bronchial hyperreactivity, we had 26 asthmatic children perform treadmill exercise challenge on two occasions 1 week apart. Both challenges were preceded by 2 control days and 1 histamine challenge day, and were followed by another histamine challenge day. Peak expiratory flow rate (PEFR) was measured hourly for 12 hours on each control day and for 12 hours after each exercise or histamine challenge. During the first week, five patients showed a late reaction (PEFR change > 15%) after exercise, which was present in only two of them the following week. These two patients, however, also showed a spontaneous fall > 15% of PEFR from baseline during the other control study days. A similar pattern was seen in two other patients who had a late response during the second exercise challenge but not during the first. No significant change occurred in histamine PC-20 FEV1 between before and after the exercise challenges. An apparent late asthmatic response after exercise challenge may represent a within-day fluctuation in pulmonary mechanics that develops spontaneously in children with asthma.

Respiratory virus infection and airway hyperreactivity in children

A significant portion of infants and young children develop acute lower airway obstruction (wheezing) accompanying viral lower respiratory infections. These wheezing‐associated respiratory illnesses, particularly bronchiolitis, are often associated with evidence of prolonged airway obstruction and airway hyperreactivity following the initial infection. The factors that determine the type of clinical infection that initially develops and long‐term respiratory consequences of this infection are complex, including the genetic background of the child, the age at the time of infection, the respiratory virus involved, and environmental factors such as exposure to cigarette smoke. Several animal models have been developed to describe the pathophysiology of viral respiratory infection and have helped to define several potential mechanisms for the resulting airway obstruction. Data from these studies and studies in humans emphasize the importance of the immune system and of neural modulation of airway smooth muscle tone in determining the outcome of respiratory virus infection. These observations also help define the pivotal role of the airway epithelium in the regulation of airway smooth muscle tone and the host inflammatory response in the airway. Consequently, the interplay of host and environmental factors, as well as the relative importance of the different mechanisms potentially active in airway obstruction, determine the acute clinical outcome of infection for an individual child and the propensity of that child to develop recurrent episodes of wheezing (asthma).

Bronchial hyperreactivity in children with Marfan syndrome

Marfan syndrome is known to have pulmonary manifestations such as pneumothorax. There have been few previous studies of pulmonary function tests and none of bronchial hyperreactivity. Therefore, pulmonary function tests were performed in 11 children with Marfan syndrome and 11 normal children. Bronchial responsiveness was tested in ten of the Marfan patients by methacholine challenge test and response to bronchodilator. Because of disproportionate length of legs in Marfan patients, an "ideal" standing height was calculated from sitting height. Pulmonary function tests, as absolute values or as percent predicted based on "ideal" height, were not different in Marfan patients and normals, although a few individual patients had abnormal function (mostly airway obstruction and hyperinflation). Response to methacholine challenge was positive on forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25 and 75% VC (FEF25-75%), and FEF50%, in 37.5%, 60%, and 70% of tests respectively. A significant response to bronchodilators was obtained in 40% of patients as measured by FEV1, in 90% by FEF25-75% and in 100% by FEF50%. Pulmonary function tests after bronchodilator were significantly higher when compared with values before the bronchodilator as well as with the baseline before methacholine. Therefore, most if not all patients with Marfan syndrome had hyperreactive airways in this relatively small group of patients. Even though only one patient had a diagnosis of asthma, six more had subtle symptoms. It is concluded that tests for bronchial hyperreactivity could be part of the routine investigation in Marfan syndrome. Further studies on larger numbers of patients are still needed.

Prevention of bronchial hyperreactivity in children

Hyperresponsiveness of the bronchi is defined as an excessive reaction of bronchial mucosa to irritants that do no harm to a healthy mucosa. Measures to prevent bronchial hyperreactivity in children with asthma and other diseases remain rather ineffective at present. Though progress has been made in some areas.

The Prevalence and Predictors of Bronchial Hyperreactivity in Children and Adolescents

The Prevalence and Predictors of Bronchial Hyperreactivity in Children and Adolescents

The reproducibility and agreement of three indices of airway responsiveness to histamine in asthmatic children.

In 12 asthmatic children, aged 8-14 years, we investigated the possibility of using a provocation concentration of histamine (PC) causing a 10% or 15% fall in baseline forced expiratory volume in 1 sec (FEV1), instead of a PC20 histamine, in the assessment of bronchial hyperreactivity. Inhalation challenge tests were performed on days 6 and 7 after withdrawal of medication. PC10, PC15, and PC20 were calculated from the dose-response curves. Reproducibilities for PC10, PC15, and PC20 values for both days, determined by Student's t-test, were not significantly different. Correlation coefficients between PC20 and PC15 values on days 6 and 7 and between PC10 values on days 6 and 7 were 0.82 and 0.76, respectively; between PC20 values on day 6 and PC15 values on day 7; and between PC20 values on day 6 and PC10 values on day 7 they were 0.84 and 0.82, respectively. (P less than 0.01 for all r values). The predictive value of PC20 for PC10 and PC15 was determined by a least-squares regression line with 95% confidence intervals. Variances between PC10, PC15, and PC20 were not significantly different on either day 6 or 7. Our data show that a PC10, as well as a PC15, can be used in the assessment of the degree of bronchial hyperreactivity in children with asthma.

Clinical applications of respiratory muscle electromyographic activity. (2) Inspiratory muscle hyperreactivity in children with severe asthma.

AbstractIntercostal EMG's (EMGic) and diaphragmatic EMG's (EMGdi) were studied to evaluate the role of the inspiratory muscles in compensation for an increased load during provocation tests with methacholine. The EMG's were obtained with surface electrodes. Methacholine provocation tests were performed using an Astograph which demonstrated the dose response curve to respiratory resistance (Rrs) on an X‐Y recorder. The moving averages were analyzed in terms of the rates of rise (Xp/Ti) and peak activities (Xp). Experiments were performed on 15 asthmatics, aged 11 to 17 yrs, (6 mild and 9 severe asthmatics) and three normal subjects, aged 8 to 13 yrs. Pulmonary function values before provocation tests, except for mid‐maximal expiratory flow (MMEF), showed no significant differences among these three groups.Changes in Xp and Xp/Ti were measured at the degree of 1.5 and 2 times the initial respiratory resistance level. In severe asthmatics, the changes in Xp and Xp/Ti were significantly larger than those of mild asthmatics, especially in intercostal Xp/Ti.From our results, the severe asthmatics had respiratory muscle hyper‐reactivity compared with mild asthmatics, especially in the intercostal muscles.

Cold air challenge of airway hyperreactivity in children: Dose-response interrelation with a reaction plateau

A previous study of cold air challenge (CACh) in children with asthma produced indirect evidence for the existence of a reaction plateau. To examine directly this phenomenon, 17 children, mean age 13 1/2 years, were challenged by isocapnic hyperventilation with -10 degrees C air at 75% of maximal voluntary ventilation for 10 minutes (extended CACh [ECACh]). Each minute FEV1 and maximum expiratory flow at 25% remaining vital capacity (V25) were measured. During "recovery" these measurements were repeated every minute for 10 minutes. Analysis of the cumulative dose-response curves constructed from the measurements revealed that a reaction plateau was reached in the last minutes of the challenge by both functions in each child. Induced changes in absolute terms were similar for both functions (FEV1: -28 +/- 12% predicted; V25: -29 +/- 17% predicted), but V25 started at a lower baseline (FEV1: 81 +/- 15% predicted; V25: 48 +/- 27% predicted) and thus arrived at a higher degree of obstruction (FEV1: 53 +/- 19% predicted; V25: 19 +/- 13% predicted). Together with the reaction plateau developing faster for V25, this indicated a dose-response influenced by baseline small airway obstruction. Although the size of the reaction differed from one child to the other (FEV1: -5% to -50% predicted; V25: -4% to -77% predicted), interindividual variability in the development of the reaction decreased toward the end of the challenge and was minimal at the plateau and in the early minutes of "recovery."(ABSTRACT TRUNCATED AT 250 WORDS)

DOSE RESPONSE CURVES TO COLD AIR CHALLENGE (CACh) IN CHILDREN WITH ASTHMATIC AIRWAY HYPERREACTIVITY

A previous study of CACh in asthmatic children produced indirect evidence of a reaction plateau (Zach et al., Pediatr Res 18:469, 1984). In order to directly examine this phenomenon, nine boys and 8 girls (mean age 13 6/12 years) were challenged by isocapnic hyperventilation of -10°C air at 75% of MVV for 10 minutes. Each minute FEV1 and Vmax25%VC were measured. During recovery these measurements were repeated every minute for 10 minutes. Analysis of the cumulative dose-response curves constructed from these measurements revealed that a maximum reaction plateau was reached by both PFT-parameters in each child. The reaction plateau for Vmax25%VC was reached somewhat earlier than for FEV1. This, the more abnormal baseline and lower absolute value at maximum reaction for Vmax25%VC with comparable maximum changes for both tests, indicate a dose response markedly influenced by the baseline small-airway obstruction. By identifying a reaction plateau, CACh offers a new parameter for outlining the individual dimensions of airway hyperreactivity in children with asthma.

The effect of ketotifen on bronchial hyperreactivity in childhood asthma

Eighteen children with perennial bronchial asthma with an average age of 9.6 yr were studied with respect to the protective effect of ketotifen on bronchial hyperreactivity. All children included demonstrated bronchial reversibility after inhalation of salbutamol, and the methacholine challenge produced a decrease of the forced expiratory volume during the first second of at least 20% in the concentration interval of 0.25 mg/ml to 4.0 mg/ml. The study was double-blind with patients divided into two parallel groups treated for 12 wk with ketotifen or placebo. Methacholine provocation tests were performed every fourth week during this period. No differences between the challenges before and during the treatment period were found in either group, nor were any differences found between the ketotifen and placebo groups. Long-term treatment with ketotifen does not appear to alter the bronchial hyperreactivity in children with bronchial asthma.