The preventive effects of natural adjuvants, G2 and G2F on tracheal responsiveness and serum IL-4 and IFN-? (th1/th2 balance) in sensitized guinea pigs

OBJECTIVE: The effects of natural adjuvants on lung inflammation and tracheal responsiveness were examined in sensitized guinea pigs. METHODS: The responses of guinea pig tracheal chains and the serum levels of interleukin-4 and interferon-gamma were examined in control pigs and three other groups of guinea pigs: the sensitized group and two other sensitized groups treated with either adjuvant G2 or adjuvant G2F (n = 7 for each group). Sensitization of the animals was achieved by injection and inhalation of ovalbumin. RESULTS: The results showed that sensitized animals had increased tracheal responsiveness and increased serum levels of interleukin-4 and interferon-gamma compared to controls (p<0.05 to p<0.001). Treatments with either G2 or G2F prevented the increase in tracheal responsiveness and serum interleukin-4 (p<0.01 to p<0.001). However, the serum levels of interferon-gamma and the interleukin-4-to-interferon-gamma ratio was increased in the treated groups (p<0.001 for all cases). CONCLUSIONS: These results indicate important preventive effects of two natural adjuvants, particularly G2, on the changes in tracheal responsiveness, serum cytokines and the interleukin-4-to-interferon-gamma ratio (T helper 1/T helper 2 balance) in sensitized guinea pigs. .

The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs

OBJECTIVE: To examine the preventive effect of a hydro-ethanolic extract of Nigella sativa on the tracheal responsiveness and white blood cell count in the lung lavage fluid of sensitized guinea pigs. METHODS: Three groups of guinea pigs sensitized to intraperitoneally injected and inhaled ovalbumin were given drinking water alone (group S), drinking water containing a low concentration of N. sativa extract (group S+LNS) or drinking water containing a high concentration of N. sativa extract (group S+HNS). The tracheal responses of control animals (group C) and the three groups of sensitized guinea pigs (n = 7 for all groups) to methacholine were measured by the assessment of the tracheal smooth muscle response to increasing concentrations of methacholine, and the effective concentration causing 50 percent of the maximum response (EC50) was determined. Tracheal responses to 0.1 percent ovalbumin and white blood cell counts in the lung lavage fluid were also examined. RESULTS: The tracheal response of the group S guinea pigs to both methacholine and ovalbumin was significantly higher than the response of the controls (p<0.01 for both cases). The tracheal responses of the S+LNS and S+HNS groups to both methacholine and ovalbumin were significantly decreased compared to those of the S group (p<0.05 to p<0.01). The total white blood cell and eosinophil counts in the lung lavage fluid of group S were significantly higher than those of group C (p<0.01). The white blood cell counts in both treated groups showed significant improvements (p<0.01 for both cases). CONCLUSIONS: These results demonstrate the preventive effect of the N. sativa extract on the tracheal response and lung inflammation in sensitized guinea pigs.

Gender and perception of dyspnea: The role of the variation in the forced expiratory volume in one second / Género y percepción de disnea: el rol de la variación del volumen espiratorio forzado en un segundo

During bronchoconstriction women perceive more breathlessness than men. The aims of study were 1) to evaluate if quality of dyspnea in bronchoconstriction was different in women and men 2) to assess if gender difference in the perception of dyspnea could be related to the level of bronchoconstriction. 457 subjects (257 women) inhaled methacholine to a 20% decrease in FEV1, or 32 mg/ml. Dyspnea was evaluated using the modified Borg scale and a list of expressions of dyspnea. Borg scores were recorded immediately before the challenge test baseline and at the maximum FEV1 decrease. The prevalence of descriptors of dyspnea reported by women and men was similar. Dyspnea was related to the level of FEV1 (ΔFEV1: OR 1.05, 95%CI 1.01-1.09, p 0.0095), females (OR 2.90, 95%CI 1.33-6.33, p 0.0072), younger subjects (OR 0.93, 95%CI 0.89- 0.97, p 0.0013) and body mass index (BMI) (OR 1.11, 95%CI 1.01-1.23, p 0.023). As the FEV1 fell less than 20% from baseline, only the ΔFEV1 was significantly associated with dyspnea (ΔFEV1:OR 1.15, 95%CI 1.07- 1.24, p 0.0002). Instead, if the FEV1 fell higher ≥ 20%, the presence of dyspnea was related to the degree of bronchoconstriction (ΔFEV1: OR 1.04, 95%CI 1.01-1.09, p 0.0187), females (OR 3.02, 95%CI 1.36-6.72, p 0.0067), younger subjects (OR 0.92, 95%CI 0.88-0.96, p 0.0007) and BMI (OR 1.12, 95%CI 1.01-1.23, p 0.023). The quality of dyspnea during the bronchoconstriction was similar in women and men; women showed a higher perception of dyspnea than men only when the FEV1 fell more than 20% from baseline.

Durante la broncoconstricción las mujeres perciben más disnea que los hombres. Los objetivos del estudio fueron evaluar: 1) si la calidad de la disnea durante la broncoconstricción fue diferente en mujeres y hombres, 2) si la diferencia entre sexos en la percepción de disnea podría relacionarse al nivel de broncoconstricción. 457 sujetos (257 mujeres) inhalaron metacolina hasta un descenso del FEV1 ≥ 20% o 32 mg/ml. La disnea fue evaluada mediante escala de Borg y una lista de expresiones de disnea. El Borg fue registrado en forma basal y con el máximo descenso del FEV1. La frecuencia de descriptores de disnea informados por mujeres y hombres fue similar. La disnea estuvo relacionada al grado de broncoconstricción (ΔFEV1: OR 1.05, 95%CI 1.01-1.09, p 0.0095), sexo femenino (OR 2.90, 95%CI 1.33-6.33, p 0.0072), edad (OR 0.93, 95%CI 0.89-0.97, p0.0013) e índice de masa corporal (IMC) (OR 1.11, 95%CI 1.01-1.23, p 0.023). Cuando el FEV1 cayó menos del 20%, solo el ΔFEV1 se asoció con disnea (ΔFEV1: OR 1.15, 95%CI 1.07-1.24, p 0.0002). En tanto que si el FEV1 cayó ≥ del 20%, la disnea estuvo relacionada al grado de broncoconstricción (ΔFEV1: OR 1.04, 95%CI 1.01-1.09, p 0.0187), sexo femenino (OR 3.02, 95%CI 1.36-6.72, p 0.0067), edad (OR 0.92, 95%CI 0.88-0.96, p 0.0007) e IMC (OR 1.12, 95%CI 1.01-1.23, p 0.023). La calidad de la disnea durante la broncoconstricción fue similar en hombres y mujeres; las mujeres tuvieron mayor percepción de disnea que los hombres solo cuando el FEV1 descendió más del 20%.

Protector mechanisms of the association between gastroesophageal reflux disease and asthma: experimental study in rats / Mecanismos protetores: doença do refluxo gastroesofágico e asma: estudo experimental em ratos

BACKGROUND: It is well known the association between gastroesophageal reflux disease and asthma. The hyperreactivity of the airways is a characteristic of an asthmatic. Many studies associate the increase of the airways reactivity with gastroesophageal reflux disease. AIM: In this study we have evaluated the effect of the intraluminal exposition to gastric juice of trachea on the reactivity to methacholine from rats submitted to a pulmonary allergic inflammation. METHODS: Group of rats were sensitized and challenged with ovalbumin. After 24 hours the animals were sacrificed, and their tracheae were removed to be cultured with gastric juice. The gastric juice was obtained from a donor rat. Subsequently the segments were placed into plastic plates with RPMI-1640 for incubation, under suitable atmosphere and time. After the period of incubation the segments were put into chambers for the analysis of the contractile response to methacholine. RESULTS: We observed reduction in the contractile response of trachea cultured with gastric juice from allergic rats. This result was confirmed by the pharmacological treatments with compound 48/80 and dissodium cromoglicate (mast cells blockade), L-NAME (nitric oxide inhibitor, NO), capsaicin (neuropeptides depletion) and indomethacin (ciclooxigenase inhibitor). CONCLUSIONS: Our results highlight to the existence of a complex interaction between pulmonary allergy and gastric juice in the airways. The involvement of the non-adrenergic non-cholinergic system, NO, prostanoids and mast cells are directly related to this interaction. We suggest that the reduced contractile response observed in vitro may represent a protector mechanism of the airways. Despite its presence in the human body it can not be observed due to the predominant effects of excitatory the non-adrenergic non-cholinergic system.

RACIONAL: É bem estabelecida a relação entre a doença do refluxo gastroesofágico e a asma. A hiperreatividade das vias aéreas é uma das características que o indivíduo asmático desenvolve e diversos estudos associam o aumento da reatividade das vias aéreas com o refluxo gastroesofágico. OBJETIVO: Avaliar a reatividade à metacolina de traquéia exposta intraluminalmente ao suco gástrico de ratos submetidos a inflamação alérgica pulmonar. MÉTODOS: Grupos de ratos foram sensibilizados e broncoprovocados com ovoalbumina. Após 24 horas, os animais foram sacrificados e a traquéia removida para preenchimento de seu lúmen com suco gástrico obtido de um animal doador. A seguir, os segmentos foram colocados em placas plásticas com RPMI-1640 e mantidos em estufa por 3 horas em condições ambientais adequadas. Após o tempo de incubação, os fragmentos foram montados em cubas de vidro para órgão isolado para registro isométrico de contração, através da construção de curvas concentração-efeito à metacolina. RESULTADOS: Observou-se redução da resposta contrátil em traquéia exposta ao suco gástrico proveniente de ratos alérgicos. Os tratamentos farmacológicos com composto 48/80 e cromoglicato de sódio (bloqueio de mastócitos), L-NAME (inibidor de óxido nítrico, NO), capsaicina (depleção de neuropeptídios) e indometacina (inibidor da ciclooxigenase) corroboraram esta observação. CONCLUSÕES: Os resultados apontam para a existência de complexa interação entre a alergia pulmonar e o suco gástrico nas vias aéreas, com o envolvimento do sistema não-adrenérgico não-colinérgico, NO, prostanóides e mastócitos. À luz das evidências in vivo sobre a hiperreatividade das vias aéreas na associação asma e refluxo gastroesofágico, sugere-se que a reduzida resposta contrátil detectada in vitro pode representar um mecanismo protetor das vias aéreas. A despeito de sua presença, esta redução pode não ser observada in vivo devido à proeminência dos efeitos do sistema não-adrenérgico ...

A Case of Occupational Rhinitis Caused by Porcine Pancreatic Extract Developing into Occupational Asthma

Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of alpha-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.

Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels

Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signáis that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signáis involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of reléase from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes.

Airways are More Reactive to Histamine than to Methacholine in Patients with Mild Airway Hyperresponsiveness, Regardless of Atopy

BACKGROUND: The airway muscles from allergen-sensitized animals in vitro show a heightened response to histamine, but not to carbachol. This study investigated whether the airway responsiveness to histamine in vivo is comparable to that of methacholine in human subjects with varying degrees of atopy. METHODS: One-hundred-and-sixty-eight consecutive adult asthma patients or volunteers underwent bronchoprovocation tests to both histamine and methacholine after determining their blood eosinophil counts, serum total IgE levels and skin test reactivity to 10 common aeroallergens. RESULTS: The responsiveness to histamine was significantly related to that to methacholine (r=0.609, p<0.001), but many individuals with a negative methacholine test response showed a positive response to histamine. The histamine-bronchial reactivity index (BRindex) was significantly higher than the methacholine-BRindex in subjects with a positive response to none (n=69, p<0.01) or only one (n=42, p<0.001) of histamine and methacholine, while there was no significant difference in the subjects with positive responses to both of them (n=57). The histamine-BRindex was significantly higher than the methacholine-BRindex in the subjects with mild histamine hyperresponsiveness (n=58, 1.28+/-0.01 vs. 1.20+/-0.02, respectively, p<0.001). Both histamine and methacholine responsiveness was significantly related to the atopy markers. However, the histamine-BRindex/methacholine-BRindex ratio of the atopics was not significantly different from that of the non-atopics. CONCLUSIONS: The airway responsiveness to histamine is comparable to that of methacholine in the subjects with positive responses to both histamine and methacholine, but the airway responsiveness to histamine is greater than that to methacholine in those subjects with mild airway hyperresponsiveness, regardless of atopy.

Eficácia do formoterol na reversão imediata do broncoespasmo / Efficacy of inhaled formoterol in reversing bronchoconstriction

OBJETIVO: Avaliar efetividade e rapidez de ação do formoterol liberado através de inalador para pó seco na reversão de broncoespasmo induzido pela metacolina. MÉTODOS: Avaliaram-se prospectivamente 84 pacientes com queda do volume expiratório forçado no primeiro segundo 20 por cento após inalação de metacolina. Todos estavam sob investigação de sintomas respiratórios de etiologia não definida. Foram randomizados 41 pacientes para receber 200 mcg de fenoterol spray e 43 para receber 12 mcg de formoterol sob a forma de inalador de pó seco para reversão imediata do broncoespasmo. Avaliaram-se a queda no volume expiratório forçado no primeiro segundo inicial, dose provocadora de queda de 20 por cento do volume expiratório forçado no primeiro segundo inicial, e volume expiratório forçado no primeiro segundo após cinco e dez minutos da administração dos fármacos. RESULTADOS: Não houve diferença significativa entre os grupos em relação ao sexo, idade, peso, altura, dose provocadora de queda de 20 por cento do volume expiratório forçado no primeiro segundo, volume expiratório forçado no primeiro segundo inicial e pós-metacolina. A melhora do volume expiratório forçado no primeiro segundo após uso do broncodilatador foi de 34 por cento (cinco minutos) e 50,1 por cento (dez minutos) no primeiro grupo, e 46,5 por cento (cinco minutos) e 53,2 por cento (dez minutos) no segundo. CONCLUSÃO: O efeito broncodilatador do formoterol após cinco e dez minutos da indução de broncoespasmo pela metacolina foi similar ao do fenoterol. O formoterol, além de ser um broncodilatador de longa duração, tem também rápido início de ação, sugerindo que possa ser empregado como medicação de resgate nas crises de broncoespasmo.

OBJECTIVE: To evaluate the effectiveness and onset of action of formoterol delivered by dry-powder inhaler in reversing methacholine-induced bronchoconstriction. METHODS: Patients presenting a drop in forced expiratory volume in one second > 20 percent after methacholine inhalation were included. A total of 84 patients were evaluated. All of the participating patients presented respiratory symptoms of unknown origin, which were being investigated. The patients were randomized to receive 200 æg of spray fenoterol (n = 41) or 12 æg of dry-powder inhaler formoterol (n = 43), both administered in order to achieve immediate reversal of methacholine-induced bronchoconstriction. We evaluated the decrease in forced expiratory volume in one second (in relation to the baseline value) after methacholine challenge and the dose of methacholine required to provoke a drop of 20 percent in forced expiratory volume in one second, as well as the increase in forced expiratory volume in one second (in relation to the baseline value) at five and ten minutes after bronchodilator use. RESULTS: There were no significant differences related to gender, age, weight, height or dose of methacholine required to provoke a drop of 20 percent in forced expiratory volume in one second. Nor were there any significant differences in terms of baseline or post-methacholine forced expiratory volume in one second. In the fenoterol group, the mean postbronchodilator increase in forced expiratory volume in one second increase was 34 percent (at five minutes) and 50.1 percent (at ten minutes), compared with 46.5 percent (at five minutes) and 53.2 percent (at ten minutes) in the formoterol group. CONCLUSION: The bronchodilator effect of formoterol at five and ten minutes after methacholine-induced bronchoconstriction was similar to that of fenoterol. Despite being a long-acting bronchodilator, formoterol also has a rapid onset of action, which suggests that it could be employed ...

Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

INTRODUCÃO: A isquemia/reperfusão intestinal ou hepática induz lesão pulmonar aguda em modelos animais de falência de múltiplos órgãos. O fator de necrose tumoral (TNF-a) está envolvido no mecanismo inflamatório da síndrome da angústia respiratória aguda. Embora a cascata inflamatória que leva à síndrome da angústia respiratória aguda tenha sido extensamente investigada, os componentes mecânicos desta ainda não são completamente compreendidos. Nós levantamos a hipótese de que a isquemia/reperfusão esplâncnica provoca aumento da reatividade contráctil das vias aéreas, bem como aumento do TNF-a sérico. OBJETIVO: avaliar a reatividade da musculatura lisa brônquica sob estimulação com metacolina, e medir os níveis séricos de TNF-a após isquemia/reperfusão intestinal e/ou hepática em ratos. MÉTODO: Ratos Wistar foram submetidos a 45 min de isquemia intestinal, ou 20 minutos de isquemia hepática, ou a ambas (isquemia dupla), ou controle, seguidos por 120 min de reperfusão. A resposta brônquica a concentrações molares (10-7 to 3x10-4) de metacolina foi avaliada usando-se uma preparação ex-vivo de musculatura brônquica. RESULTADOS: A resposta brônquica (g/100mg de tecido) mostrou reatividade aumentada a concentrações crescentes de metacolina na isquemia intestinal e isquemia dupla, mas não na isquemia hepática. Similarmente, o TNF-a sérico aumentou na isquemia intestinal e isquemia dupla, mas não na isquemia hepática. CONCLUSÃO: Isquemia intestinal, quer isolada ou associada à hepática, provocou hiper-reatividade da musculatura brônquica, sugerindo um possível papel da constrição brônquica na disfunção respiratória conseqüente à isquemia/reperfusão esplâncnica. Este aumento foi simultâneo ao do TNF-a sérico, porém o possível efeito causal do TNF-a na contractilidade brônquica permanece a ser determinado.

Severe Airway Hyperresponsiveness in School-aged Boys with a High Body Mass Index

BACKGROUND: An association between obesity and asthma has been reported. The prevalence of airway hyperresponsiveness (AHR), results of skin prick tests, body mass index (BMI), and asthma symptoms were examined in schoolchildren. METHODS: The results of BMI (kg/m2) determination, skin prick testing, spirometry, asthma questionnaires, and methacholine challenge tests were obtained in a cross-sectional survey of 667 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of AHR. If the PC20 was less than 16 mg/mL, the subject was considered to have methachloine mediated AHR. RESULTS: The mean BMI was 17.1+/-0.09 kg/m2. The prevalence of AHR was 42.7%. The sensitization rate to common inhalant allergens was 30.3%. PC20 in children with BMIs >or=17.1 kg/m2 was significantly lower than that in children with BMIs 17.1 kg/m2. The mean BMIs of boys and girls were not significantly different. The levels of PC20 by sex were not different. The children were grouped by sex into percentile of BMI. PC20 in boys was lower in the obese group than in the non-weight and overweight groups (p<0.05). PC20 in boys and girls with atopy was significantly lower than in those without atopy. In a multiple logistic regression model that included all of the children and adjusted for confounding variables, independent associations with AHR were seen with BMI, asthma symptoms, and atopy . CONCLUSIONS: BMI had an association with AHR in school-age boys.

Acute and Chronic Changes of Vascular Endothelial Growth Factor (VEGF)in Induced Sputum of Toluene Diisocyanate (TDI)-induced Asthma Patients

Vascular endothelial growth factor (VEGF) is a multi-functional cytokine involved in inflammation, repair and angiogenesis in asthmatic airway. This study aimed to evaluate the role of VEGF in immediate bronchoconstriction induced by TDI inhalation, and in chronic TDI-asthma patients. 11 newly diagnosed TDI-asthma patients (group I), 12 chronic TDI-asthma patients with persistent asthma symptoms followed for >4 yr and 15 unexposed healthy controls were enrolled. In group I, induced sputum and serum were collected before and 7 hr after placebo- and TDI-bronchoprovocation test (BPT). In group II, induced sputum and serum were collected every 2 yr. VEGF levels were measured by ELISA. There were no significant differences in sputum and serum VEGF levels between patients and controls. Before and after placebo and TDI-BPT, no significant changes were noted in sputum and serum VEGF levels of group I. In group II patients, sputum VEGF showed variable changes at 1-yr, then decreased significantly at 2-yr (p<0.05), while serum VEGF showed variable changes at 2-yr, which decreased significantly at 4-yr (p<0.05). These results suggest that VEGF may play a minor role in immediate bronchoconstriction after TDI-BPT. In chronic TDI-asthma, VEGF may be involved to 2 yr after the diagnosis and the contribution may decrease after then.

The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in bronchial asthma and allergic rhinitis

Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness, but results at the moment are less than convincing. The present study was conducted to evaluate the effect of immunotherapy on the degree of nonspecific bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA) and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test, allergic skin test, serum IgE and peripheral blood eosinophil counts were performed before and after 12 months or more of immunotherapy. The improved group, as determined by a shift of at least two doubling concentrations of methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR (n=13). The geometric mean of the methacholine provocational concentration (PC20) changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In conclusion, nonspecific bronchial hyperresponsiveness was improved by immunotherapy in three quarters of the allergic rhinitis cases and in about a half of the allergic bronchial asthma patients, which suggests that immunotherapy might be helpful at preventing the development of bronchial hyperresponsiveness in allergic rhinitis patients, and that it does not improve bronchial hyperresponsiveness in about a half of allergic bronchial asthma patients.

Airway Reactivity to Bronchoconstrictor and Bronchodilator: Assessment Using Thin-Section and Volumetric Three-Dimensional CT

OBJECTIVE: To determine the extent to which thin-section and volumetric three-dimensional CT can depict airway reactivity to bronchostimulator, and to assess the effect of different airway sizes on the degree of reactivity. MATERIALS AND METHODS: In eight dogs, thin-section CT scans were obtained before and after the administration of methacholine and ventolin. Cross-sectional areas of bronchi at multiple levels, as shown by axial CT, proximal airway volume as revealed by three-dimensional imaging, and peak airway pressure were mea-sured. The significance of airway change induced by methacholine and ventolin, expressed by percentage changes in cross-sectional area, proximal airway volume, and peak airway pressure was statistically evaluated, as was correlation between the degree of airway reactivity and the area of airways. RESULTS: Cross-sectional areas of the bronchi decreased significantly after the administration of methacholine, and scans obtained after a delay of 5 minutes showed that normalization was insufficient. Ventolin induced a significant increase in cross-sectional areas and an increase in proximal airway volume, while the effect of methacholine on the latter was the opposite. Peak airway pres-sure increased after the administration of methacholine, and after a 5-minute delay its level was near that of the control state. Ventolin, however, induced no significant decrease. The degree of airway reactivity did not correlate with airway size. CONCLUSION: Thin-section and volumetric spiral CT with three-dimensional reconstruction can demonstrate airway reactivity to bronchostimulator. The degree of reactivity did not correlate with airway size.

Bronchial response to methacholine inhalation challenge in families with and without asthma

This study included 140 subjects; 20 asthmatic patients, 60 as first degree relative to asthmatics and 60 from non-asthmatic families. The results showed that all asthmatic patients were highly responders to methacholine inhalation challenge with a PD20 FEV1 less than 600 ug. The responders in asthmatic families were seven cases, but in non- asthmatics families, only three cases responded to methacholine inhalation challenge. This indicated that bronchial hyperresponse to methacholine is not due to environmental factor alone, but a combination of both environmental and genetic factors are responsible for bronchial hyperreactivity

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P> 0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, N G -nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect

Broncoprovocaçäo inespecífica com metacolina em crianças antes e durante a queima dos canaviais em Catanduva-SP / No-specific bronchoprovocation with metacholine in children before and during sugar cane burning in Catanduva-SP

A queima dos canaviais promove a liberaçäo de poluentes para a atmosfera que podem influenciar a hiperreatividade brönquica (HB). Objetivos: Avaliar se a queima dos canaviais interfere com a HB de crianças asmáticas e controles "normais", por meio de testes de broncoprovocaçäo com metacolina; e se interfere nas medidas de funçäo pulmonar. Métodos: Submetemos 22 crianças asmáticas (A) (7 a 14 anos) e 12 crianças controles (C) "normais" (8 a 13 anos) à broncoprovocaçäo inespecífica com metacolina, antes e durante a queima dos canaviais. Utilizamos concentraçöes crescentes de metacolina inalada: 0,025; 0,25; 1,0; 2,5; 10,0; 25,0 mg/ml, expressando os resultados em CP dos VEF (concentraçäo cumulativa capaz de produzir queda de 20 por cento do volume expiratório forçado no primeiro segundo). Resultados: A média da CP das crianças A foi significantemente menor...

Eficácia da flunisolida em aerossol no tratamento da asma em crianças e adolescentes / Efficacy of flunisolide aerosol in the treatment of asthma in children and adolescents

A eficácia da flunisolida em aerossol na dose de 500 mcg, duas vezes ao dia, com aerocâmera de 300 ml foi verificada em 30 pacientes, com idades entre 8 e 16 anos, portadores de asma atópica, moderada e persistente. O estudo era prospectivo e aberto, com avaliaçöes mensais durante três meses de funçäo pulmonar, hiper-reatividade à metacolina (PC20), escore clínico, cortisol plasmático matinal, dosagem da proteína catiônica (ECP), número de eosinófilos no sangue e culturas de orofaringe para Cândida. O tratamento com flunisolida reduziu significativamente o número de crises: 53 por cento sem crises no primeiro mês, para 77 por cento sem crises no terceiro mês, diminuindo também o número de eosinófilos no sangue e os níveis séricos de ECP. Os níveis de cortisol plasmático e a média geométrica de metacolina näo se alteraram durante o tratamento. Houve melhora da funçäo pulmonar e a freqüência de candidíase näo aumentou com o uso de flunisolida. Como efeito indesejável, 66 por cento dos pacientes referiram gosto amargo na boca. Em conclusäo, a flunisolida é eficaz em crianças e adolescentes com asma moderada persistente.

Efectos sobre el valor de PC20 al emplear VEF1 mas alto o mas bajo para su cálculo / Effect on PC20 calculated using the highest or the lowest FEV1 value

Existe poca información en niños acerca de cual valor de VEF1, si el más alto o el más bajo, debe ser considerado para el cálculo de la PC20 de metacolina. Veinte niños asmáticos atópicos, previamente entrenados hasta alcanzar maniobras de capacidad vital forzada reproducibles, fueron estudiados para determinar si había diferencias en las PC20 de metacolina calculadas con los mayores o los menores valores de VEF1. Las diferencias entre las PC20 usando uno u otro valor de VEF1 no fueron estadísticamente significativas (ANOVA). Hubo una correlación significativa entre las PC20 calculadas con ambos métodos (r= 0,93, p< 0,05). El presente estudio demuestra que, en niños asmáticos entrenados hasta lograr maniobras de capacidad vital forzada reproducible, la PC20 puede ser determinada usando el valor más alto o más bajo de VEF1

Effect of inhaled corticosteroids on bronchial hyperresponsiveness in patients with mild asthma.

We studied the effect of inhaled budesonide on bronchial hyperresponsiveness (BHR) in twenty mild asthmatic patients. The study was conducted as a randomized, double-blind, placebo-controlled study. Before entering the study, the patients performed methacholine inhalation challenge (MIC) using a reservoir method to assess BHR. Then, they were randomly allocated to receive budesonide turbuhaler (200 micrograms/dose) or placebo turbuhaler two inhalations, twice daily for eight weeks. During the study, each patient recorded daily asthma score and daily number of puffs of beta 2 agonist and they were assessed at weeks 4 and 8. At the end of the treatment, MIC was repeated again. Patients receiving budesonide showed a significant improvement in airway responsiveness compared with those receiving placebo (p < 0.05). They also showed a significant improvement in asthma severity score and a significant decrease in beta 2 agonist bronchodilator use. This study also suggested that inhaled corticosteroids may be the primary treatment in patients, even with mild asthmatic and well-controlled symptoms.