Lung function and bronchial responsiveness in children who had infantile bronchiolitis

A number of studies have shown that children who had infantile bronchiolitis are at increased risk of recurrent episodes of wheezing. A genetic predisposition to atopy is mentioned in some studies and is contested by others. Lung function abnormalities and increased bronchial responsiveness (BR) have been described after infantile bronchiolitis. We investigated children who had had the clinical syndrome of bronchiolitis during infancy and compared them with asthmatic and healthy children of the same age regarding bronchial caliber, smooth muscle tone, and responsiveness to histamine. Lung function was measured by forced oscillometry. We found that most children with current symptoms had either decreased baseline bronchial caliber, increased bronchial smooth muscle tone, or increased BR. These patients are comparable to mild asthmatics. The children without current symptoms are comparable to healthy children in these respects. Recurrent respiratory symptoms after bronchiolitis should be regarded as mild asthma and treated as such.     

Lung function decline in bronchial asthma

STUDY OBJECTIVE: We evaluated the longitudinal changes in lung function and the factors associated with FEV(1) changes over time in a sample of asthmatic subjects. SETTING: FEV(1) measures were recorded every 3 months over a 5-year follow-up period. To compare all subjects independently of body size, FEV(1) values were normalized for the subject's height at the third power. We evaluated the possible effect of age, baseline FEV(1), disease duration, and FEV(1) variability on the rate of change of FEV(1). PATIENTS: We studied 142 subjects with asthma diagnosed on the basis of validated clinical and functional criteria. RESULTS: FEV(1) showed a linear decay with aging in each subject. For a subject 1.65 m in height, the median overall FEV(1) decay was 40.9 mL/yr. FEV(1) decay slopes were significantly influenced by age and sex, being steeper in younger male subjects. A significant interaction was found between age and baseline FEV(1): the FEV(1) decay was significantly higher among younger asthmatics with a poorer baseline functional condition. A longer disease duration was associated with a lower FEV(1) slope. FEV(1) variability was strongly associated with an increased rate of FEV(1) decline. CONCLUSIONS: FEV(1) decline in patients with bronchial asthma is significantly influenced by baseline FEV(1), disease duration, and FEV(1) variability. Moreover, the rate of FEV(1) decline seems to increase in younger subjects only when the baseline function is poorer.     

Increased level of bronchial responsiveness in inactive children with asthma

We estimated the association between bronchial responsiveness and hours of exercise per week in children with and without asthma. A random sample of school children (n = 2188), 6-16 years old, was enrolled in a cross-sectional study of asthma in Oslo using the ISAAC questionnaire. Lung function and bronchial responsiveness (BR) using methacholine was measured in a random sample of 80 children with asthma, wheeze and no asthma/no wheeze. The relation between hours of exercise per week and BR [log (DRS)] was estimated by linear regression. Sex and age were included as covariates. Hours of exercise were categorized in: none, 30 min, 1 h, 2-3 h, 4-6 h and 7 h or more. The mean values of log (DRS) were different in the low and high exercise groups for children with asthma (P = 0.02), whereas there was no effect of exercise on BR for children without asthma. BR increased with decreasing hours of exercise per week in children with asthma. The bronchial responsiveness decreased with 0.11 (95% CI -0.20, -0.01) pr unit in scale. This pattern was not present in children without asthma.The results suggest that there is a relation between hours of exercise per week and bronchial responsiveness in children with asthma.     

Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

Mycoplasma (M.) pneumoniae has been associated with exacerbation of symptoms in asthmatic school children and adults; and an etiological role in asthma has been suggested. The purpose of this study was to investigate whether infection with M. pneumoniae in early childhood has a long-term influence on lung function and bronchial responsiveness. In a retrospective, clinical cohort-study children younger than 5 years-of-age when PCR-tested for M. pneumoniae were enrolled. Sixty-five children with clinical symptoms suggesting infection with M. pneumoniae during an epidemic season completed a clinical follow-up examination including lung function testing (28 PCR-positive and 37 PCR-negative). In addition to the PCR-test for M. pneumoniae all respiratory tract specimens were additionally tested for other atypical bacteria and for viruses by PCR. Lung function was measured as specific airway resistance by whole-body plethysmography and bronchial hyperresponsiveness was assessed by cold, dry air hyperventilation. Neither baseline lung function nor bronchial response to cold dry air hyperventilation differed between M. pneumoniae-positive and -negative children: mean baseline lung function were 1.17 versus 1.21 (kPa sec), P = 0.45; and mean change in specific resistance was 13% versus 9%, P = 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection.     

Repeatability of bronchial responsiveness to mannitol dry powder in children with asthma

Our objective was to determine the repeatability of bronchial responsiveness to mannitol dry powder (MDP) as an objective marker of asthma in children. MDP challenge was performed in children with stable asthma at the same time of the day on two separate occasions within a week. The test was terminated after a 15% fall of forced expiratory volume in 1 sec (FEV1) and the provocative dose to produce a 15% fall in FEV1 (PD15) were calculated. Seventeen children (aged 9-16 years) on inhaled corticosteroids (200-1,500 mcg) were studied. Mean baseline FEV1 before the challenges were 95% (81-119) and 96% (74-121), respectively, with a standard deviation of differences of 5.2%. PD(15) values ranged from 7-387 mg, with a geometric mean of 38 mg for the first and 49 mg for the second test. Of the 17, all but two pairs of tests achieved a PD15 within one dose of capsules. Four children had a negative challenge on two occasions. A high relative reliability was reflected by a concordance coefficient of 0.86. In conclusion, MDP is a convenient challenge which is easy to administer and is well-tolerated by children. It is a highly reproducible test of airway responsiveness in children with moderate to severe persistent asthma on inhaled corticosteroids within 7 days under laboratory conditions.     

肺水通道蛋白与支气管哮喘

通过对肺水通道蛋白(aquaporins,AQPs)的结构、分布及功能的研究,发现AQPs与支气管哮喘(简称哮喘)之间存在密切关系,其中,AQP1参与了肺部水的转运、哮喘急性炎症期的发病机制,AQP3可能在保持气道表面的液体平衡及防止细菌人侵、气道重塑等方面起着重要的作用,AQP4可能参与了哮喘条件下黏液分泌的调控,AQP5则与气道高反应性、气流受限、调节气道水稳态有关,这些为哮喘的诊断及治疗开辟了新的思路.     

肺水通道蛋白与支气管哮喘

通过对肺水通道蛋白(aquaporins,AQPs)的结构、分布及功能的研究,发现AQPs与支气管哮喘(简称哮喘)之间存在密切关系,其中,AQP1参与了肺部水的转运、哮喘急性炎症期的发病机制,AQP3可能在保持气道表面的液体平衡及防止细菌入侵、气道重塑等方面起着重要的作用,AQP4可能参与了哮喘条件下黏液分泌的调控,AQP5则与气道高反应性、气流受限、调节气道水稳态有关,这些为哮喘的诊断及治疗开辟了新的思路.     

Pulmonary function changes induced by bronchial asthma in children, teenagers and adults

The study has established that pulmonary dysfunctions in bronchial asthma are less marked in children and teenagers than in adults. The magnitude of pulmonary dysfunctions are chiefly determined by the severity of bronchial asthma. There was a less close relationship of pulmonary function to the duration of bronchial asthma. There was no association of the severity of pulmonary dysfunctions with the duration of bronchial asthma.     

Effect of azelastine, an antiasthmatic drug, on bronchial responsiveness in patients with bronchial asthma

This study was designed to clarify whether azelastine, an antiasthmatic drug, could favorably alter bronchial responsiveness in patients with bronchial asthma. To estimate bronchial responsiveness, methacholine challenge was performed in 21 patients with bronchial asthma. After the first examination, all patients were treated for eight weeks with azelastine, 2 mg twice daily. After four and eight weeks' treatment, methacholine challenge was repeated. After eight weeks' treatment, Dmin, an index of bronchial sensitivity, was increased significantly, and after four weeks an insignificant increase was observed. The RrsC, SGrs/GrsC, indices of respiratory resistance and bronchial reactivity, respectively, did not change significantly during eight weeks' treatment. Recently various chemical transmitters, especially leukotrienes, were shown to be closely related to the genesis of bronchial asthma. Accordingly, the effect of azelastine observed here might be ascribed to its antagonizing action on leukotriene. Since bronchial hyperresponsiveness is a critical etiologic factor in bronchial asthma, long-term administration of azelastine might help to modify the disease's basic pathophysiologic conditions.     

Lung function and bronchial responsiveness after bronchoalveolar lavage and bronchial biopsy performed without premedication in stable asthmatic subjects.

We evaluated tolerance, safety, and effects on lung function and bronchial responsiveness of BAL (4 x 50 ml) combined with BB (three to five specimens) performed without premedication in 13 mild and stable asthmatics and eight healthy volunteers. All subjects tolerated bronchoscopy procedures well and without serious side effects. During procedures, no supplemental oxygen was administered and no ECG abnormalities were noted. The PEFR was measured before and immediately after bronchoscopy and at 5-min intervals up until recovery. The maximal percentage fall in PEFR after bronchoscopy was significantly greater in asthmatics (23.1 +/- 13.9 percent) compared to normal subjects (7.8 +/- 8.2 percent, p less than 0.01). Changes in PEFR returned to baseline values within 120 min in all asthmatics. The tcPO2 was recorded at baseline, during and after bronchoscopy. In both groups, a significant change in tcPO2 was measured during the infusion of BAL aliquots, and persisted throughout the procedure. A significant difference in asthmatics compared to healthy subjects was evident during BB and at the end of the procedure (p less than 0.05). In asthmatics, M challenge was performed on three different days over a three-week period prior to bronchoscopy, and was repeated at intervals of 2, 6, and 24 h following procedure. The PC20 M values measured before bronchoscopy were found to have a very high reproducibility (intraclass correlation coefficient = 0.93). The PC20 values measured during experiment times after bronchoscopy were not significantly different from baseline values. These data demonstrate that in mild and stable asthmatics, BAL combined with BB can be safely performed following administration of only local anesthesia. In carefully selected asthmatic subjects, transient bronchoconstriction and a lowering of oxygen tension can be induced by BAL and BB, whereas changes in bronchial responsiveness are more unlikely to occur.     

Longitudinal changes of pulmonary function and bronchial responsiveness in cough-variant asthma treated with bronchodilators alone.

Cough due to cough-variant asthma (CVA) responds well to bronchodilators such as beta 2 adrenergic agonists. The aim of this study was to assess longitudinal changes of pulmonary function and bronchial responsiveness in CVA, which was treated with bronchodilators alone. Seventeen CVA patients recorded intensity and frequency of cough every day. Spirometry and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20) were measured in the run-in period and after cough almost completely relieved on therapy. Cough score had improved within 2 weeks after the initiation of bronchodilator therapy. Forced expiratory volume in one second (FEV1) was significantly increased from 2.7 +/-0.7 L in the run-in period to 2.8+/-0.7 L after improvement of cough. However, the geometric mean (GSEM) PC20 value did not change from the run-in period [1542 (GSEM 1.29) microg/mL] to the time of improvement [2600 (GSEM 1.43) microg/mL]. Mildly increased bronchial responsiveness in CVA does not improve when only bronchodilator therapy is carried out. Because bronchial hyperresponsiveness has been shown to be a risk factor for typical asthma onset from CVA, the effect of inhaled corticosteroids on the longitudinal changes in bronchial responsiveness should be examined.     

Lung function in 3-5-year-old children with cystic fibrosis

It is well established that the lung disease of CF can occur early in life and may progress through the preschool years when accurate lung function assessment has been challenging to perform. We hypothesized that respiratory inductive plethysmography (RIP) and spirometry could be effectively performed in 3-6-year-old children and could be used to assess both longitudinal changes in lung function and the acute changes that occur during exacerbation of pulmonary disease. Both RIP and spirometry were equally feasible; however, the success rate for spirometry gradually increased with age to become higher than that for RIP in the 6-year-old subjects. Forty-four subjects were studied longitudinally and demonstrated significant increases in FVC, FEV(1), and FEV(0.5), but not in FEF(25-75) or RIP variables. There were significant differences in FVC, FEV(1), and phase angle (a measure of thoracoabdominal asynchrony) during exacerbations of lung disease. Although both RIP and spirometry were able to show differences in lung function in subjects with acute clinical worsening, spirometry was more robust in demonstrating change in lung function longitudinally and in children who had an exacerbation of lung disease.     

Lung function and symptom perception in children with asthma and their parents

A large proportion of children with asthma are managed without recourse to specialized care, and treatment decisions are based solely on symptoms as reported by the children and their parents. We investigated 90 school-age children with the diagnosis of asthma and their accompanying parent to evaluate whether we can obtain better information by using three different means of asking for asthma symptoms: a questionnaire for children (QSR(children)), "smilies," and a visual analogue scale for children (VAS(children)). Furthermore, we analyzed the relationship between these symptom reports and lung function results. Finally, we attempted to determine whether performing a lung function test contributes relevant information toward improving asthma management. Multiple linear regression adjusted for age and gender showed a significant relationship between VAS for children and forced expiratory volume in 1 sec (FEV(1)) (P = 0.047) and maximal expiratory flow at 50% of forced vital capacity (MEF(50)) (P = 0.037). Neither age, gender, QSR for children, "smilies for children" nor all the parents' scores showed a significant association with lung function measurement in the regression model. Subgroup analysis with Spearman's rank correlation coefficients by age group revealed significant correlation in children <10 years between VAS for children, QSR for parents, smilies for parents, and the lung function parameters FEV(1), and MEF(50). Above age 10 years there was no correlation at all, with the accuracy correlation ranging from -0.04 to +0.21. Our data demonstrate that reported symptoms do not reliably correlate with lung function results in asthmatic children and the childrens' parents, and correlation is dependent on the instrument used for symptom evaluation. In children, the VAS, and in parents, the QSR were the most valuable means of obtaining best information on asthma symptoms. This underlines the importance of supplementing information on asthma symptoms with lung function measurements to more reliably assess the severity of asthma.     

Effect of inhaled steroid therapy on exhaled nitric oxide and bronchial responsiveness in children with asthma.

Inhaled steroid therapy is reported to reduce the level of exhaled nitric oxide (eNO), but the effects of inhaled corticosteroids (ICS) on bronchial hyperresponsiveness (BHR) have been controversial. The aim of this study was to determine the effects of ICS on the relationship between eNO and BHR. Twenty-six children with asthma were recruited, including 14 children who were receiving ICS (ICS group) and 12 who were not (ICS-naive group). The fractional exhaled nitric oxide concentration (FE(NO)) was examined by the recommended online method. To evaluate BHR, an acetylcholine challenge test was performed. In the ICS-naive group, FE(NO) was significantly correlated with PC20 (p < 0.05, r = -0.70), but not in the ICS group. In conclusion, FE(NO) was significantly correlated with BHR in the ICS-naive group, but this relationship was not present in the ICS group. Our results suggest that the use of ICS should be taken into consideration when evaluating the relation between BHR and airway inflammation.