Bronchial hyperreactivity: pathogenesis and treatment options

This review is written to summarize and critically analyze pathogenesis of bronchial hyperreactivity (BHR) as an underlying outcome for suitable treatment options. It describes and discusses the role of genetic predisposition, inflammatory mediators and other endogenous factors (growth factors, nuclear transcription factors), neural regulation and proinflammatory neurotransmitter in the pathogenesis of BHR. Based on these data it provides brief insight into the treatment options, which could be applied to minimize symptoms of respiratory diseases characterized by BHR and successfully diminish the pathogenesis pathways involved.

Preventive Effect of an Extract of Terminalia avicennioides on Acetylcholine-Induced Tracheoconstriction in Wistar Strain Rats

Asthma is one of the most common chronic respiratory pathologies worldwide. The cost of its treatment, particularly for populations in developing countries like Senegal, requires an alternative which consists of developing research into new therapeutic approaches with the use of plants from traditional pharmacopoeia. The objective of this study was to determine whether the hydroalcoholic extract of Terminalia avicennioides leaves has a preventive effect on the constriction of tracheal smooth muscle induced by Acetylcholine in Wistar strain rats. Methods: The species used in our experiments were male Wistar rats aged between 12 and 14 weeks. Rings of rat trachea were suspended in isolated organ chambers connected to tension sensors. Two pharmacological agents were used: acetylcholine, for its constrictor effect and adrenaline, for its dilating effect on the pulmonary trachea. Our plant material consisted of a hydroalcoholic extract of Terminalia avicennioides leaves. The experimental protocol was that of the preventive model which consisted of impregnating these rings with the extract at a defined concentration then testing its contractility in the presence of Acetylcholine which was the contractile agonist used in this study. The preventive effect of the extract was studied with an Acetylcholine contraction range on rings pre-incubated with Terminalia avicennioides extract. Results: The results showed that Acetylcholine contracts the trachea and the increase in its contractility was dependent on the dose of Ach added cumulatively (10−5 to 4 × 10−5 mol/l). The administration of the hydroalcoholic extract of Terminalia avicennioides leaves led to a modification of the contractile response to Acetylcholine. Indeed, this extract induced a significant attenuation of the contractile responses of the treated tracheal rings compared to those untreated. Conclusion: Terminalia avicennioides had a relaxing effect on tracheal smooth muscle and this effect could play an important role in the prevention of bronchial hyperreactivity in certain respiratory diseases, particularly asthmatic disease.

Bronchial hyperresponsiveness in childhood: A narrative review

Bronchial hyperresponsiveness(BHR) is an important but not asthma-specific characteristic and can be assessed by direct and indirect methods, based on the stimulus causing airway obstruction. BHR has been proposed as a prognostic marker of asthma severity and persistence, and may also be used to control pharmacological management of asthma. The most recent data on the prevalence and development of BHR in childhood and its predictive value for subsequent asthma development in late adolescence and adulthood is discussed in this review. According to the BHR-related scientific articles written in the English language and indexed in the publicly searchable PubM ed database, the prevalence of BHR varies based upon the methods used to assess it and the population examined. In general, however, BHR prevalence is reduced as children grow older, in both healthy and asthmatic populations. While asthma can be predicted by BHR, the predictive value is limited. Reduced lung function, allergic sensitization, female sex, and early respiratory illness have been identified as risk factors for BHR. The collective studies further indicate that BHR is a dynamic feature related to asthma, but asymptomatic BHR is also common. Ultimately, the prevalence of BHR varies depending on the population, the environment, and the evaluation methods used. While both the methacholine challenge and the exercise test may predict asthma in adolescence or early adulthood, the predictive value is higher for the methacholine challenge compared to the exercise test. The collective data presented in the present study demonstrate how BHR develops through childhood and its relation to bronchial asthma.

High-frequency electrical stimulation of cervical vagi reduces airway response to methacholine

AIM: To test whether high-frequency electrical stimulation(HES) of the bilateral cervical vagus nerves reduces the airway responses to methacholine(MCh).METHODS: Guinea pigs were pretreated with saline(Sal, n = 9) or ovalbumin(Ova, n = 10) aerosol for two weeks(5 min/d, 5 d/wk) and subsequently anesthetized, paralyzed, tracheotomized and artificially ventilated. Both total lung resistance(RL) and dynamic pulmonary compliance(Cdyn) were recorded. In addition, the effects of vagal low-frequency electrical stimulation(LES, monophasic, 50 Hz) and HES(monophasic and biphasic, 1 and 2.5 kH z) for about 10 s or 2 min on the responses of RL and Cdyn to MCh aerosol-induced bronchoconstriction were compared in both groups of guinea pigs. In a few guinea pigs, the impact of bivagotomy on the RL responses to MCh was assessed.RESULTS: Before MCh challenge, LES, but not HES, significantly increased RL by about 30%(P < 0.01) and decreased Cdyn by about 20%(P < 0.01) similarly in both groups. MCh aerosol for 2 min elevated RL and diminished Cdyn more in Ova- than Sal-treated animals(RL: 313% ± 52% vs 113% ± 17%, P < 0.01; Cdyn:-56% ± 7% vs-21% ± 3%, P < 0.01). During MCh-induced airway constriction, LES further enhanced, but HES decreased RL and this decrease was greater in Ova-(about 45%) than Sal-treated animals(about 34%, P < 0.01) with little change in cardiovascular activity. On the other hand, LES further reduced whereas HES increased Cdyn more in Ova-(about 20%) than Sal-treated animals(about 13%, P < 0.01). In addition, bivagotomy almost eliminated the RL and Cdyn responses to MCh. CONCLUSION: We conclude that vagal HES is able to alleviate the bronchoconstriction induced by MCh in anesthetized guinea pigs, likely via reversible inhibition/blockade of vagal conduction.

The influence of vitamin D3 on airway inflammation and osteopontin expression in cough variant asthma rats

Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment group,each group with 10 rats.The CVA model was induced by intraperitoneal injection combined with aerosolized ovalbumin(OVA),the treatment group was given 100 mg/ml of vitaminD330 minutes before challenge by administered orally.Airway hyperreaction were measured by airway resistance after inhalation of acetylcholine(Ach).Wright-Gimsa staining was used to observe the inflammatory cells in bronchoalveolar lavage fluid(BALF).HE and PAS were used to observe the morphological changes of lung tissue.OPN expression was detected by immunohistochemistry.Results:1)Airway hyperreaction:airway resistance after inhalation Ach in model group and treatment group were significantly higher than that in blank group(P<0.01),airway resistance in treatment group were lower than that in model group(P<0.01);2)Classification of inflammatory cells:The percentage of macrophages,lymphocytes,neutrophils,and eosinophils in the BALF of the model group and the treatment group were increased compared with the blank group(P<0.01),furthermore,the number of treatment group were lower than the model group(P<0.05);3)Morphological changes of lung tissue:a large amount of inflammatory cells and goblet cell proliferation were observed in the lung tissue of the model group,and these changes were slight in treatment group compared with model group;OPN expression in lung tissue:The expression of OPN in model and treatment group were increased compared with blank group(P<0.05),and the treatment group was lower than that of model group(P<0.05).The OPN content was positively correlated with the percentage of inflammatory cells in BALF(P<0.05).Conclusions:Vitamin D3 can reduce airway hyperreaction and airway inflammation in CVA rats.The mechanism may be related to the intervention of OPN expression in lung tissue.

Cold Agglutinin Disease Prevalence and Immunoglobulin M levels in Patients with Splenomegaly from Endemic Areas for Malaria in Rwanda

Background: Inhabitants from malaria endemic zones often present with enlarged spleen, mainly due to hyper reactive malarial splenomegaly (HMS), and it is seen more commonly associated with elevated levels of Immunoglobulin M (IgM). Cold agglutinin disease is an acquired autoimmune hemolytic anemia (AIHA) that is usually due to cold-reacting IgM autoantibodies directed against red cell antigens. The study was conducted in response to the observed high frequency of transfusion dependent anemia in patients with splenomegaly from malaria endemic zones in southern province of Rwanda. The objectives of this study were to determine the prevalence of cold agglutinin disease and to assess the distribution of IgM antibodies among these patients. Methodology: This was a descriptive, cross-sectional study conducted over a period of six months from June 2016 to December 2016. The study enrolled adult population from malaria endemic areas of the southern province of Rwanda with unexplained splenomegaly. Blood samples for testing IgM levels, cold agglutinin, FBC, and markers of hemolysis were collected from peripheral health settings and analyzed at the laboratory of Butare University Teaching Hospital. Results: During the study period, we enrolled 188 participants with enlarged spleen. One hundred twenty-five (66%) were females and 34% were males. The mean (±SD) age of the study participants was 35.6 ± 15.2 years. Out of 188 participants, only 4.8% were found with significantly positive Cold Agglutinin Titer (CAT) (≥1:64) and 84% of participants were found to have elevated serum IgM level. Hemoglobin level, white blood count and platelets count decrease with severity of splenomegaly, while IgM level increases with spleen size. Conclusion: Among patients with splenomegaly from malaria endemic areas, IgM levels correlate with the stages of splenomegaly while cold agglutinin disease plays a small role in the etiology of anemia.

Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin

BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P

Clinical Observation of the Therapeutic Effect of Ginkgo Leaf Concentrated Oral Liquor on Bronchial Asthma

Objective: To determine the effects of Ginkgo leaf concentrated oral liquor (GLC) on airway inflammation. Methods: Airway hyperreactivity, clinical symptoms and pulmonary functions of asthma patients were determined. Results: In contrast to placebo group, GLC significantly reduced airway hyperreactivity (P<0. 05) and improved clinical symptoms (P < 0. 05 ) and pulmonary functions (P < 0. 05 ) of the asthmatic patients. Conclusion: GLC is an effective drug of anti-airway inflammation.

Application of Ultra-low-dose Incremental Gn Protocol in Controlled Ovarian Hyperstimulation of the Patients with Ovary Hyperreaction

Objective To explore the clinical outcome of ultra-low-dose incremental protocol in the controlled ovarian hyperstimulation （COH） for the ovary hyperreaction patient. Methods A prospective, randomized, controlled study was conducted between June 2006 and February 2008 on 120 women who underwent COH. The patients＇ clinic outcomes were compared between ultra-low-dose incremental protocal （experimental group, n=60） and other ovulation stimulating protocols （control group, n=60）. Results The mean number of large follicles （≥14 mm） on the day of oocytes retrivaling, the mean number of harvested oocytes and the incidence rate of OHSS were significantly lower in experimental group. However, the gonadotropin stimulating time was significantly longer in experimental group. And the rate of leading follicle punctuation was also higher in this group when compared with control group. The clinical pregnant rate, the mean number of gonadotropin ampoules, the cancel rate were similar in the two groups. Conclusion The application of ultra-low-dose incremental protocal in the COH for the ovarian hyperreaction patients is able to effectively reduce the risk of occurrence of OHSS under the precondition of assurance of pregnancy rate. It is a safe and more effective COH program.