© Borgis - New Medicine 1/2001, s. 42-47
Bronchial reactivity and initial airway status in asthmatic children
Department of Paediatric Respiratory Diseases and Allergology, Medical University of Warsaw Hospital, Warsaw, Poland
Bronchial hyper-reactivity (BHR) to various stimuli is a characteristic feature of asthma. However, it is not always possible to perform a bronchial provocation test (BPT) to assess bronchial reactivity. There is no general agreement as to whether the result of a BPT can be predicted on the basis of routine lung tests. The aim of the study was evaluation of the relationship between BPT results and baseline lung function tests, especially assessing the status of small bronchi in children suffering from asthma.
The investigated group comprised 139 children aged 7 to 17 years, with episodic, mild, or moderate asthma. Lung function was assessed on the basis of spirography, flow-volume curve, and airway resistance. Bronchial challenges were carried out with carbachol.
The results showed a good correlation between a BPT result and baseline lung function. Children with impaired initial lung tests had more pronounced bronchial hyper-reactivity. This relationship was closest in the group of children with obstruction of the small bronchi. Analysis of the correlation showed a highly significant relationship between baseline lung function tests and the degree of bronchial reactivity (PC20). The highest significance was observed for MEF50 and MEF25 (p<0.001).
We conclude that small bronchi tests in children with asthma can predict the results of a bronchial challenge with high probability.
Bronchial hyper-reactivity (BHR) to different allergic and non-allergic stimuli is regarded as one of the basic features of asthma. However, it is not always possible to detect BHR in children suffering from asthma. Some data show that it is observed only in about 80% of asthmatic children, and its absence does not exclude asthma. Other authors stress that the use of improper diagnostic tools or misinterpretation indicates an absence of hyper-responsivity in asthma, and that there is no asthma without BHR. Unfortunately BHR is not its exclusive attribute. It is observed in such diseases as cystic fibrosis, atopic rhinitis, chronic lung diseases, congestive heart diseases or even atopic dermatitis. Common viral bronchitis can also induce bronchial hyper-responsivity lasting several weeks. The prevalence of BHR in those diseases is lower, and the course seems to be less severe than in bronchial asthma. Therefore the presence of considerable bronchial hyper-responsivity in patients with ambiguous clinical symptoms of asthma can be decisive in the diagnosis of asthma.
A significant decrease in bronchial obstruction after use of a bronchodilator is also found in bronchial hyperreactivity in asthma. However, in the asymptomatic period when there is no bronchoconstriction the usefulness of bronchial provocation tests (BPT) as a diagnostic tool or for the evaluation of the efficacy of anti-inflammatory treatment is rather questionable. A bronchial challenge requires a proper respiratory laboratory and some experience in the interpretation of BPT results. Sometimes it is impossible to perform the test because of a refusal by the patient or the patient´s parents. Therefore it seems valuable to know if it is possible to predict the results of a bronchial challenge on the basis of routine lung function tests.
The aim of the study was to investigate the correlation between lung function indices, especially describing small bronchi patency, and the results of bronchial provocation tests in asthmatic children.
Material and Methods
The investigated group comprised 139 asthmatic children (44 girls and 95 boys) aged 7 to 17 years (mean 9.4 ± 3.5 yrs). The children were patients of our Outpatient Clinic for children with bronchial asthma. All of them were suffering from an episodic, mild, or moderate form of the disease. The diagnosis was established on the basis of the patient´s clinical history, skin prick tests, lung function tests, and immunological investigations.
Method of study
At the moment of the study children were asymptomatic and had been free of acute respiratory tract infections for at least 6 weeks, without any subjective signs of bronchial obstruction, and appeared well on physical examination on the day of the challenge. The course of the disease allowed for a temporary cessation of treatment, which might influence BPT results according to ERS guidelines (26). Baseline lung function tests, including vital capacity (VC), forced expiratory volume in one second (FEV1), maximal expiratory flows for 50% and 25% of forced vital capacity (MEF50, MEF25), and airway resistance (Raw), were performed immediately prior to investigation. We also evaluated indices derived from a flow-volume curve - i.e. mean flow time at 50% of VC (T50), being the result of dividing the half VC by MEF50, and mean flow time at 25% of VC (T25), being the result of dividing the quarter VC by MEF25. The surface under the second half of the flow volume curve (S50) was also calculated. Patients with bronchial obstruction (decreased FEV1%VC below 74%) were not included in the study. A bronchial provocation test was performed next with carbachol. Bronchial challenges were done between 9 and 11 a.m. during the winter months in three consecutive years.
Carbachol chloride solution in buffered saline was prepared immediately before the challenge. An initial inhalation of nebulized, chloride saline preceded each challenge. Subsequently two-fold concentrations starting at 156 mg/ml up to 5mg/ml of carbachol were used during two-minute-long tidal breathing nebulizations (Pari Standard nebulizer). VC, FEV1, MEF50, MEF25, Raw (Body test, Jaeger) and Rrs were measured following each nebulization. Inhalations were provided at 5-minute intervals until the maximal concentration of carbachol was achieved or a 20% fall in FEV1 had occurred. The provocative concentration that induced a 20% fall in FEV1 (PC20) was calculated.
According to the baseline FEV1, MEF50 and MEF25 results, patients were divided in the following manner.
? Group A - with FEV1 higher than predicted for height.
? Group B - with FEV1 equal to or lower than predicted for height.
The division of the children according to their small bronchi test results was done in two ways:
? Group I - with MEF50 or MEF25 higher than predicted for height.
? Group II - with MEF50 or MEF25 equal to or lower than predicted for height and
? Group N - with MEF50 or MEF25 within normal ranges.
? Group O - with MEF50 or MEF25 below normal ranges (value predicted for height less 2 standard deviations) - i.e. a group of children with small bronchi obstruction.
Children were also divided into 5 groups according to their bronchial provocation test results, grading bronchial reactivity. The method used by Woolcock et al. (29) was used with our own modification based on carbachol molar weight.
1. Very severe hyper-reactivity (logPC20 < 4.99).
2. Severe hyper-reactivity (logPC20 between 5.0 and 7.07).
3. Moderate hyper-reactivity (logPC20 between 7.08 and 8.46).
4. Mild hyper-reactivity (logPC20 between 8.47 and 10.37).
5. Normal reactivity (logPC20 > 10.37).
Parental informed consent was obtained before each test. Warsaw Medical School Ethics Committee approved the study protocol.
Results of lung function tests were expressed as standard deviation scores (SDS). For standardization, the predicted values for Polish girls and boys were taken from Haluszka and co-workers, while for MEF50 and MEF25 the predicted values were taken from Zapletal et al. (31) and for T50, T25 and S50 the predicted values were from our own laboratory.
Values of PC20 carbachol were logarithmically transformed to normalize their distribution. Differences between groups were calculated with an unpaired Student´s T-test. The relationship between pre-challenge lung function indices and log PC20 was tested by linear regression analysis. The level of statistical significance was taken as a p-value of less than 0.05.
In the investigated group of asthmatic children 34 patients had MEF50 above the average for the population (group I, SDS <=0). Their bronchial reactivity (log PC20=9.1508 ±2.9218) was significantly lower (p<0.001) than the rest of the investigated patients (group II, SDS<0) (log PC20=6.9261 ±2.6217) (Fig. 1a - page 44). Similarly, the group I contained 41 asthmatics with MEF25 above that predicted (SDS <=0), and showed a lower hyper-reactivity (log PC20=8.8591 ±3.2846) (p<0,001) than group II with lower initial MEF25 values (log PC20=6.8897 ±2.4427) (Fig. 1b - page 44).
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