MECHANISMS OF BRONCHIAL HYPERREACTIVITY
\nIN HEALTHY PERSONS<\/p>\n
V.N.Solopov, S.B.Dogadkina
\nMedical center ‘Pulmonologist’, Moscow, Russia<\/p>\n
KEY WORDS<\/p>\n
Bronchial hyperresponsiveness. Microcirculation. Sinus arrhythmia. Nebulized distilled water test.<\/p>\n
ABSTRACT<\/p>\n
The interrelation between the bronchial hyperresponsiveness, degree of sinus arrhythmia and the state of the microcirculatory bed was studied in 64 teenagers — 38 males and 26 females aged 15-16 years. The examination program consisted of the evaluation of the microcirculatory bed state,expression of the respiratory (sinus) arrhythmia and pulmonary function (PF) investigation with bronchoprovocation nebulized distilled water test.
\nPhotomicrographs of the microcirculatory bed were taken on a intravital slit bulboconjunctive microscope with a camera attachment. Morphometric measurments were performed on negative pictures by means of the graduated photomagnifier with an object-micrometer scale.
\nThe degree of the sinus arrhythmia was evaluated by the ECG second standard deviation after recording of 15 cardiac complexes PQRST. For each person all the intervals R-R were measured and Means \u00b1 SD were calculated. The degree of the sinus arrhythmia was expressed by the coefficient of variation (CV):<\/p>\n
SD
\nCV = ——- x 100%
\nMean<\/p>\n
The PF investigation and evaluation of the bronchial hyperresponsiveness using the nebulized distilled water test were carried out by means of the computer spirometer as follows: 1) initial evaluation of the PF indices; 2) 3 min inhalation of a distilled water aerosol by means of the highly productive (4 ml\/min) ultrasonic nebulizer with particle size less than 5 mm.; 3) repeated evaluation of the PF indices. The bronchoprovocation test was considered to be positive in cases, when one of the PF indices decreased by more than 10% of predicted values and it was associated with all the indices decreasing.
\nIt was found that bronchial hyperresponsiveness is closely connected with microcirculatory bed state and the degree of sinus arrhythmia.<\/p>\n
INTRODUCTION<\/p>\n
One of the characteristic feature of bronchial asthma pathogenesis determined inadequate response to various factors (execise, hyperventilation, forced respiration, fog, cold air etc.) is bronchial hyperresponsiveness \/1, 2\/. Primary hyperresponsiveness (without bronchial inflammation or allergy) in number of cases can play the key role in asthma development \/ 2 \/. Since any constitutional and inherent mechanisms determine the primary bronchial hyperresponsiveness appearance \/1, 2\/ it is of interest to carry out a deeper study with regard to prevention of asthma development and progression.
\nAs it is known the most probable mechanisms of hyperresponsiveness are being considered any intrinsic, parasympathetic or sympathetic disorders as well as increased delivery of different bronchoconstrictor agents (inflammatory mediators, different peptides, allergenes etc.) \/1, 2\/ causing bronchial mucosa inflammation. On the other hand all the inflammatory processes are closely connected with microcirculation disturbances increasing capillar permeability and causing bronchial mucosa edema \/1\/. With this in mind we consider that it is of theoretical interest to study the interrelation of certain physiological mechanisms and their contribution in the primary hyperresponsiveness phenomenon. One of the method using for estimation of non-specific bronchial reactivity in asthmatics is inhalation test with distilled water \/3\/. We decided to use nebulized distilled water test in healthy persons and to find any relationship between bronchial hyperresponsiveness, state of the microcirculatory bed and expression of parasympathetic (vagal) activity manifesting by the phenomenon of the respiratory (sinus) arrhythmia \/4\/.<\/p>\n
SUBJECTS AND METHODS<\/p>\n
We examined 64 teenagers aged 15-16 years (38 males and 26 females), non-smokers, occupying physical culture on common program with no history of respiratory or cardiovascular diseases. All the subjects were investigated in the morning hours. The examination program consisted of the evaluation of the microcirculatory bed state, expression of the respiratory (sinus) arrhythmia and pulmonary function (PF) investigation with bronchoprovocation nebulized distilled water test.
\nPhotomicrographs of the microcirculatory bed were taken on an intravital slit bulboconjunctive microscope with a camera attachment using the analogous Kodak black & white film with a resolution 300 lines\/mm. The original micrographs were taken in each person two times. Morphometric measurments were performed on negative pictures by means of the graduated photomagnifier with an object-micrometer scale.
\nThe degree of the sinus arrhythmia was evaluated by recording of the ECG second standard deviation as follows: in resting respiration 15 cardiac complexes PQRST were recorded. Then for each person all the intervals R-R were measured and Means \u00b1 SD were calculated. The degree of the sinus arrhythmia was expressed by the calculating of the coefficient of variation (CV):<\/p>\n
SD
\nCV = —— x 100%
\nMean<\/p>\n
The PF investigation and evaluation of the bronchial hyperresponsiveness using the nebulized distilled water test were carried out by means of the computer spirometer (Vitalograph-Compact) as follows:
\n1) initial evaluation of the PF indices:Vmax 25%, Vmax 50% and Vmax 75% — maximum expiratory flow at 25, 50 and 75%, respectively, of forced vital capacity;
\n2) 3 min inhalation of a distilled water aerosol by means of the highly productive (4 ml\/min) ultrasonic nebulizer with particle size less than 5 m.;
\n3) repeated evaluation of the PF indices.
\nAll the PF indices were expressed as a percent of predicted values \/ 5 \/. The bronchoprovocation test was considered to be positive in cases, when one of the PF indices decreased by more than 10% of predicted values and it was associated with all the indices decreasing.
\nThus the examination program included measuring the following parameters:
\n1) AI and AII — diameter of arterioles of the first and second divisi ons (mm);
\n2) CV — coefficient of variation (in per cent) as a degree of sinus ar rhythmia expression;
\n3) Vmax 25%, Vmax 50% and Vmax 75% — maximum expiratory flow, respectively 25, 50 and 75% of forced vital capacity;
\n4) ReVmax 25%, ReVmax 50% and ReVmax 75% — bronchial response («+» — increase; «-» — decrease) to inhalation nebulized distilled water test.
\nStatistical analysis of the obtained results was performed by applying the methods of variation statistic and correlation analysis. The large standard deviations and abnormal distribution determined the use of nonparametric methods: Wilkoxon’s unpaired test and Spearman’s correlation analysis.<\/p>\n
RESULTS<\/p>\n
According to the results of bronchoprovocation test with nebulized distilled water all the subjects were divided into two groups (table 1).<\/p>\n
Table 1. The results of subjects’ investigation
\n(X \u00b1 SEM)<\/p>\n
| Investigated groups<\/td>\n | Vmax 25%<\/td>\n | Vmax 50%,<\/td>\n | Vmax 75%,<\/td>\n | AI, mcm<\/td>\n | AII, mcm<\/td>\n | ReVmax 25%<\/td>\n | ReVmax 50%<\/td>\n | ReVmax 75%<\/td>\n | CV<\/td>\n<\/tr>\n | ||||||||||||||||||||||||||||
| the 1st \n(n=22)<\/td>\n | 92,9 \n\u00b14,36<\/td>\n | 101,2 \n\u00b15,34<\/td>\n | 113,3 \n\u00b18,48<\/td>\n | 30,6 \n\u00b10,72<\/td>\n | 21,6 \n\u00b10,79<\/td>\n | -11,7**W \n\u00b12,09<\/td>\n | -17,2**W \n\u00b12,37<\/td>\n | -19,7**W \n\u00b12,73<\/td>\n | 5,06*W \n\u00b10,46<\/td>\n<\/tr>\n | ||||||||||||||||||||||||||||
| the 2nd \n(n=42)<\/td>\n | 89,9 \n\u00b12,71<\/td>\n | 97,3 \n\u00b14,15<\/td>\n | 110,9 \n\u00b17,08<\/td>\n | 29,9 \n\u00b10,87<\/td>\n | 20,8 \n\u00b10,64<\/td>\n | -0,98 \n\u00b11,35<\/td>\n | -1,45 \n\u00b11,46<\/td>\n | 6,6 \n\u00b14,2<\/td>\n | 6,14 \n\u00b10,58<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n *W \u2014 Wilkoxon’s test (* \u2014 p<0.05, ** \u2014 p<0.01) the 1st group vs. the 2nd group.<\/p>\n The first group comprised 22 persons with bronchial hyperreactivity resulted in decreasing of flow-volume curve indices. In 7 out of these 22 teenagers we found slight clinical symptoms of bronchoconstriction: cough and wheezes revealed by auscultation. In one youth aged 15 years after 3 min inhalation we observed an appearance of acute expiratory dyspnea which was arrested by the inhalation of one dose (0.2 mg) of fenoterol. His PF indices dynamics was the follows: a) initially — Vmax 25% = 101%, Vmax 50% = 109% , Vmax 75% = 99%; b) on the background of bronchoprovocation test — Vmax 25% = 60%, Vmax 50% = 54%, Vmax 75% = 41%; c)20 min after fenoterol inhalation — Vmax 25% = 102%, Vmax 50% = 108% and Vmax 75% = 99% of predicted values. Table 2. The results of correlation analysis in teenagers with bronchial hyperresponsiveness<\/p>\n \n
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