Factores asociados con la presencia de hiperreactividad bronquial en rinitis alérgica de niños y adolescentes / Factors associated with presence the bronchial hyperresponsiveness in allergic rhinitis the children and adolescent

Objetivos: la hiperreactividad bronquial (HRB) inespecífica está presente en el asma bronquial así como en otras enfermedades respiratorias y no respiratorias. Fue nuestro objetivo investigar la prevalencia de HRB inespecífica a la metacolina y los factores asociados con su presencia en un grupo de niños y adolescentes con rinitis alérgica (RA). Material y métodos: se incluyeron 25 niños y adolescentes de ambos sexos, entre 7 y 19años de edad, con diagnóstico de rinitis alérgica, sin asma bronquial previo o actual. Los pacientes fueron clasificados en dos grupos: metacolina positivos (MTC +) y metacolina negativos (MTC Ä) según reactividad bronquial manifiesta a la prueba de broncoprovocación con metacolina (umbral diferencial PC20FEV1=16 mg/ml). Se estudiaron comparativamente los niveles hemáticos de IgE y eosinófilos, IgA secretoria, eosinófilos en secreción nasal, presencia de anormalidades en la radiografía de senos paranasales y, por interrogatorio, el tiempo de evolución de RA, condición de fumador pasivo y antecedentes hereditarios de asma bronquial. Resultados: la prevalencia de HRB a la metacolina fue del 56 por ciento: 14 de 25 pacientes tuvieron un PC-20FEV1ó16 mg/ml...

Factores asociados con la presencia de hiperreactividad bronquial en rinitis alérgica de niños y adolescentes / Factors associated with presence the bronchial hyperresponsiveness in allergic rhinitis the children and adolescent

Objetivos: la hiperreactividad bronquial (HRB) inespecífica está presente en el asma bronquial así como en otras enfermedades respiratorias y no respiratorias. Fue nuestro objetivo investigar la prevalencia de HRB inespecífica a la metacolina y los factores asociados con su presencia en un grupo de niños y adolescentes con rinitis alérgica (RA). Material y métodos: se incluyeron 25 niños y adolescentes de ambos sexos, entre 7 y 19años de edad, con diagnóstico de rinitis alérgica, sin asma bronquial previo o actual. Los pacientes fueron clasificados en dos grupos: metacolina positivos (MTC +) y metacolina negativos (MTC Ä) según reactividad bronquial manifiesta a la prueba de broncoprovocación con metacolina (umbral diferencial PC20FEV1=16 mg/ml). Se estudiaron comparativamente los niveles hemáticos de IgE y eosinófilos, IgA secretoria, eosinófilos en secreción nasal, presencia de anormalidades en la radiografía de senos paranasales y, por interrogatorio, el tiempo de evolución de RA, condición de fumador pasivo y antecedentes hereditarios de asma bronquial. Resultados: la prevalencia de HRB a la metacolina fue del 56 por ciento: 14 de 25 pacientes tuvieron un PC-20FEV1ó16 mg/ml...

Oxatomide modifies methacholine- and exercise-induced bronchoconstriction in asthmatic children.

Oxatomide is a potent inhibitor of both the release and effects of allergic mediators and is similar to calcium antagonists in chemical structure. It prevents histamine release by inhibiting not only the increase in calcium intake, but also intracellular calcium release. We investigated its effect on methacholine-induced and exercise-induced bronchoconstriction in asthmatic children. Methacholine challenges were performed after oral administration of 0.88 mg/kg oxatomide or placebo in nine asthmatic children in a double-blind placebo-controlled study. Respiratory thresholds were improved in seven patients and log PC20 in the oxatomide group (6.65 +/- 1.34 micrograms/mL) was significantly higher than that in the placebo group (5.74 +/- 1.04 micrograms/mL) (P < .05). Exercise challenges were performed after oral administration of 1.5 mg/kg oxatomide or placebo in eight asthmatic children in a double-blind placebo-controlled study. Oxatomide produced acute bronchodilatation with 6.1% improvement on an average in FEV1. The mean maximal % fall obtained by oxatomide was 13.5%, while that by placebo was 22% (P < .05). These results indicate that oxatomide reduces nonspecific bronchial hyperresponsiveness.

Determinación del umbral de reactividad bronquial a la metacolina entre niños asmáticos y normales / Determination of the threshold of bronchial reactivity to the methacholine betwen asthmaticsand normals children

Se realizaron pruebas de provocación bronquial con metacolina a un grupo de 66 niños con asma bronquial, entre 6 y 17 años, y un grupo control de 19 niños normales, entre 7 a 14 años, con la finalidad de establecer el umbral de reactividad bronquial mediante la determinación de los índices de sensibilidad y especificidad. Se utilizó el método de aerosolización continua de concentraciones doblemente crecientes de bromuro de metacolina entre 0.008 y 128 mg/ml, expresando los resultados con la PC20 VEF1 -concentración que provoca la caída del 20% en el Volumen Espiatorio Forzado en el primer segundo- mediante interpolación lineal y logarítmica, estudiándose la correlación entre los valores obtenidos por ambos métodos. Obtuvimos una alta correlación entre los valores de PC20 VEF1 lineal y logarítmico (r=0.99; p<0.001). Se estableció en 20 mg/ml el umbral de reactividad bronquial teórico, obteniéndose una sensibilidad y especificidad del 90%. Con 25 mg/ml se mejoró la sensibilidad que alcanzó el 96% sin mayor detrimento de la especificidad que se redujo al 84%. Concluímos que la determinación del umbral de reactividad bronquial a la metacolina inhalada, establece límites relativos entre la población de niños asmáticos y normales; según nuestras observaciones podrá considerarse la posibilidad diagnóstica de asma bronquial cuando exista reactividad bronquial al agente colinérgico a concentraciones menores de 25 mg/ml

Determinación del umbral de reactividad bronquial a la metacolina entre niños asmáticos y normales / Determination of the threshold of bronchial reactivity to the methacholine betwen asthmaticsand normals children

Se realizaron pruebas de provocación bronquial con metacolina a un grupo de 66 niños con asma bronquial, entre 6 y 17 años, y un grupo control de 19 niños normales, entre 7 a 14 años, con la finalidad de establecer el umbral de reactividad bronquial mediante la determinación de los índices de sensibilidad y especificidad. Se utilizó el método de aerosolización continua de concentraciones doblemente crecientes de bromuro de metacolina entre 0.008 y 128 mg/ml, expresando los resultados con la PC20 VEF1 -concentración que provoca la caída del 20% en el Volumen Espiatorio Forzado en el primer segundo- mediante interpolación lineal y logarítmica, estudiándose la correlación entre los valores obtenidos por ambos métodos. Obtuvimos una alta correlación entre los valores de PC20 VEF1 lineal y logarítmico (r=0.99; p<0.001). Se estableció en 20 mg/ml el umbral de reactividad bronquial teórico, obteniéndose una sensibilidad y especificidad del 90%. Con 25 mg/ml se mejoró la sensibilidad que alcanzó el 96% sin mayor detrimento de la especificidad que se redujo al 84%. Concluímos que la determinación del umbral de reactividad bronquial a la metacolina inhalada, establece límites relativos entre la población de niños asmáticos y normales; según nuestras observaciones podrá considerarse la posibilidad diagnóstica de asma bronquial cuando exista reactividad bronquial al agente colinérgico a concentraciones menores de 25 mg/ml

[Bronchial hyperreactivity and heart failure]. / Hyperréactivité bronchique et insuffisance cardiaque.

A moderate to severe bronchial hyperresponsiveness to methacholine is frequently observed in patients with left heart failure. This bronchial obstruction can be prevented by inhalation of methoxamine, an alpha-adrenergic vasoconstrictor agent. The mechanisms of this hyperresponsiveness include a direct vasodilating effect of methacholine on bronchial vessels and a contractile effect of an airway smooth muscles. This bronchoconstriction is the consequence of a direct effect of methacholine and a contractile effect of an extravased mediators and of an increased vagal tone due to the stimulation a bronchial afferent nerves. The role of bronchial hyperresponsiveness in cardiac dyspnea is currently under investigations.

The use of the dose-response curve in the assessment of normal and asymptomatic asthmatic patients.

We studied bronchial reactivity, the slope of the dose-response curve to inhaled methacholine, in normal subjects (N), young asthmatics with normal respiratory resistance (Rrs) (YAL), young asthmatics with high Rrs (YAH), and old asthmatics with high Rrs (OAH) by three different methods: linear reactivity (slope of the linear cumulative dose-conductance (Grs = 1/Rrs) curve), timed reactivity (slope of the log concentration-Grs or time-Grs curve), and log reactivity (slope of the log cumulative dose-Grs curve). There were significant differences in linear reactivity between the N and the three asthmatics but no difference among the three asthmatic groups. On the other hand, both timed and log reactivities showed significant differences between the three asthmatic groups. Log and timed reactivities corrected by baseline Grs did not differentiate the YAL from the YAH but showed a significant difference between the YAH and OAH. This study suggests that timed and log reactivities may be better indices of bronchial reactivity than linear reactivity because they differentiate asthmatics, and that bronchial reactivity in asthmatics may be dependent on not only baseline airway caliber in asthmatics but also other factors such as atopic status or age.

Recurrent asthma induced by toluene diisocyanate.

A worker developed toluene diisocyanate induced asthma in 1974. On reassessment, 11 years after leaving the chemical plant where toluene diisocyanate was produced, he had no respiratory symptoms and normal bronchial reactivity in response to methacholine, and showed no reaction when challenged with a subirritant concentration of toluene diisocyanate. He developed asthma within five months of returning to the workplace. Repeat challenge testing showed bronchial hyperreactivity to methacholine and to the specific sensitising agent, toluene diisocyanate. This clinical pattern could be due to underlying toluene diisocyanate sensitivity with resolution and reappearance of hyperresponsiveness to methacholine and toluene diisocyanate reactivity associated with workplace toluene diisocyanate exposure. Alternatively, this worker may have developed sensitisation to toluene diisocyanate anew.

Isotonic nebulized disodium cromoglycate provides better protection against methacholine- and exercise-induced bronchoconstriction.

In 21 asthmatic subjects we determined whether inhalation of an isotonic solution of disodium cromoglycate (DSCG) would result in better protection against bronchial provocation with methacholine or exercise than the standard hypotonic solution of DSCG. Pretreatment with isotonic DSCG resulted in significantly greater reduction in exercise-induced bronchospasm (10 patients) than with hypotonic DSCG. In addition, the dose of methacholine required to induce a decrease greater than 20% in FEV1 was significantly higher following pretreatment with isotonic DSCG compared with placebo or hypotonic solution of the drug (11 patients). We conclude that nebulized isotonic DSCG provides better protection against exercise- and methacholine-induced bronchoconstriction than does the standard solution. Our findings suggest that the use of an isotonic solution of DSCG would be beneficial in the management of asthmatic patients.

An assessment of methacholine inhalation tests in elderly asthmatics.

We have assessed the feasibility and value of measuring nonspecific bronchial responsiveness to methacholine in investigation of asthma in the elderly. Results from duplicated tests in 20 subjects aged 65-82 years were expressed as dose provoking a 20% decrement in 1 second forced expiratory volume (PD20.FEV1) or peak expiratory flow (PD20.PEF). Repeatability for PD20.FEV1 was satisfactory but less good than in younger subjects, 95% confidence limits being 0.39-2.57 and 0.52-1.91, respectively, x initial PD20. For PD20.PEF, confidence limits were wider (0.26-3.91 x initial PD20) but multiple PEF measurements were better tolerated than those of FEV1, which commonly caused fatigue and dizziness. PD20.FEV1 and PD20.PEF correlated closely (r = 0.95, P less than 0.0001) and both predicted bronchodilatation following a 6-week course of inhaled corticosteroid and beta agonist. This was not predicted by the response to a single dose of beta agonist. We conclude that measurement of bronchial responsiveness is feasible and clinically valuable in elderly subjects.

[Calcium inhibitors in asthma]. / Les inhibiteurs calciques dans l'asthme.

Calcium ions are involved in many activities of cells, especially muscle contraction, mediator release and enzyme activities. It has been suggested that regulation of the cellular calcium could be important in the pathogenesis of asthma. In several studies, the efficiency of calcium antagonists on basophil degranulation and on asthma that is induced by pharmacological drugs (histamine, metacholine) or by exercise or allergens, has been investigated. A few studies on long-term treatment of asthma with calcium antagonists have been published. It seems that there is a place for the use of calcium inhibitors in the treatment of asthma, but it remains to fix the dosages and routes of administration and to identify the most effective products.

Passive transfer of methacholine sensitivity from man to monkey.

A model of human allergic disease, in which nonhuman primates were infused with serum from allergic humans and challenged with appropriate antigen, was used to determine whether the animals also develop hyperreactive airways characteristic of asthma. Anesthetized monkeys were insufflated with increasing concentrations of methacholine aerosol, and changes in pulmonary function were measured. Airway reactivity as assessed by the dose of methacholine aerosol culminating in apnea was determined after infusion of serum from allergic or nonallergic humans or with heated allergic serum. A comparison of the results indicated that only infusion of unheated serum from allergic humans resulted in an increase in airway reactivity to aerosolized methacholine. These results suggest that a factor in the serum of allergic humans may play a role in the hyperreactivity of airways characteristic of asthma.

Limited bronchoconstriction to methacholine using partial flow-volume curves in nonasthmatic subjects.

We investigated whether the plateau of the dose-response to nonsensitizing stimuli, such as methacholine, could be explained by the airway dilation that follows lung inflation in nonasthmatics. We used maximal expiratory partial flow-volume curves to measure the response of the airways to doubling doses of inhaled methacholine up to 256 mg/ml (a noncumulative dose of 340 mumol delivered to the mouth during tidal breathing) in 12 nonasthmatics on 2 days. Maximal expiratory complete flow-volume curves and FEV1 were also obtained along with the partial curves. Flows were measured at 40% of control vital capacity using the complete (V40c) and the partial (V40p) curves. A maximal response plateau of 2 or more doubling concentrations was demonstrated in all subjects based on V40p, and in 10 subjects based on FEV1. The level of the plateau was the highest for the V40p (mean +/- SD = 65 +/- 19% of baseline), intermediate for V40c (45 +/- 22%), and the lowest for FEV1 (16 +/- 11%). There was more than a 100-fold range in responsiveness expressed as the provocative concentration to cause a 40% fall of baseline in V40p (PC40); the lower the PC40, the higher the level of the plateau. All the results were reproducible between the 2 days. We also investigated whether the plateau may have been due to a tachyphylactic effect of cumulative doses of methacholine. The maximal response after increasing concentrations of methacholine up to 256 mg/ml was not different from the response obtained after a single dose of 256 mg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway responses to sulfur dioxide and methacholine in asthmatics.

Sulfur dioxide (SO2) is a common air pollutant found in the workplace. Considerable variation exists in the airway responses of asthmatics to the inhalation of SO2. To determine if such variation among asthmatics is related to nonspecific airway reactivity, we compared the threshold doses of methacholine and SO2 required to produce significant changes in flow rates at 60% of the vital capacity below total lung capacity on the partial expiratory flow volume curve in a group of eight mildly asthmatic subjects. A significant correlation between the dose of SO2 and the dose of methacholine required to produce bronchoconstriction (r = .86, p less than .05) was observed, suggesting that there is a relationship between the response to SO2 and the response to methacholine in mildly asthmatic individuals. More generally, nonspecific airway hyperreactivity may help to predict untoward airway responses to inhaled SO2 in the workplace.

Bronchial hyperresponsiveness to methacholine after exercise in asthmatics.

We studied the effect of exercise on bronchial responsiveness to methacholine in 10 asthmatics. Bronchial responsiveness to methacholine was compared before and 20 minutes after exercise. Although five out of 10 asthmatics showed exercise-induced bronchoconstriction (EIB), nine out of 10 asthmatics became more hypersensitive after exercise, irrespective of EIB.