Increase In Bronchial Hyperresponsiveness Research Articles

Dose-Response Effect of Saccharomyces cerevisiae UFMG A-905 on the Prevention of Asthma in an Animal Model.

Probiotics should be administered in adequate amounts to confer health benefits. Probiotic dose-response studies are still missing. Saccharomyces cerevisiae UFMG A-905 prevented asthma development; however, the ideal dose has not been investigated. We evaluated the optimal dose and administration regimen of S. cerevisiae UFMG A-905 in the prevention of asthma. Male Balb/c mice were sensitized intraperitoneally with ovalbumin (OVA) and challenged with OVA intranasally. Mice received, via gavage, daily or alternate-day S. cerevisiae UFMG A-905. In daily regimen, different concentrations (107, 108, or 109CFU/mL) were given 10days before OVA sensitization and during challenges. In alternate-day regimen, a concentration of 109CFU/mL was administered three times per week for 5weeks, starting 2weeks prior to the first sensitization. After the last challenge, in vivo bronchial hyperresponsiveness and airway and lung inflammation were assessed. OVA-challenged mice, when compared to saline-challenged mice, presented a significant increase in bronchial hyperresponsiveness and airway and lung inflammation. Daily and alternate-day administration of 109CFU/mL of S. cerevisiae UFMG A-905 significantly reduced bronchial hyperresponsiveness; lower concentrations of S. cerevisiae UFMG A-905 did not significantly reduce bronchial hyperresponsiveness. Daily regimen with the highest concentration significantly reduced total cell number, eosinophil count in the BAL, and the levels of IL-4, IL-5, and IL-13. Daily administration of S. cerevisiae UFMG A-905 at 107 and 108CFU/mL and alternate-day regimen did not significantly decrease airway and lung inflammation. S. cerevisiae UFMG A-905 led to a significant attenuation of bronchial hyperresponsiveness and lung inflammation in a dose-dependent manner.

Sex in Respiratory and Skin Allergies.

A bulk of literature demonstrated that respiratory allergy, and especially asthma, is prevalent in males during childhood, while it becomes more frequent in females from adolescence, i.e., after menarche, to adulthood. The mechanisms underlying the difference between females and males are the effects on the immune response of female hormones and in particular the modulation of inflammatory response by estrogens, as well as the result of the activity of various cells, such as dendritic cells, innate lymphoid cells, Th1, Th2, T regulatory (Treg) and B regulatory (Bregs) cells, and a number of proteins and cytokines, which include interleukin (IL)-4, IL-5, IL-10, and IL-13. As far as sexual dimorphism is concerned, a gender difference in the expression profiles of histamine receptors and of mast cells was demonstrated in experimental studies. A critical phase of hormone production is the menstrual cycle, which often is associated with asthma deterioration, as assessed by worsening of clinical symptoms and increase of bronchial hyperresponsiveness. In asthmatic woman, there is a high risk to develop more severe asthma during menstruation. The higher prevalence of asthma in females is confirmed also in the post-menopause age, but the underlying mechanisms are not yet understood. In pregnancy, asthma may worsen but may also improve or remain unchanged, with no significant difference in frequency of these three outcomes. For allergic rhinitis, the available studies indicate, likewise asthma, a male predominance in prevalence in childhood that shifts to a female predominance in adolescence and adulthood, but further investigation is needed.

Inflammatory and Oxidative Stress Markers in Experimental Allergic Asthma.

Ovalbumin-induced allergic lung inflammation (ALI) is a condition believed to be mediated by cytokines, extracellular matrix remodeling, and redox imbalance. In this study, we evaluated pulmonary function together with inflammatory markers as interleukin-4 (IL-4), myeloperoxidase (MPO), eosinophil cells, and redox markers in the lungs of BALB/c mice after ovalbumin (OVA) sensitization and challenge. Our results showed an increase in bronchial hyperresponsiveness stimulated by methacholine (Mch), inflammatory cell influx, especially eosinophils together with an increase of high mobility group box 1 (HMGB1) and altered lipid peroxidation (LP) and antioxidant defenses in the OVA group compared to the control group (p≤0.5). Thus, we demonstrated that OVA-induced ALI altered redox status concomitantly with impaired lung function, which was associated with HMGB1 expression and proteolytic remodeling. Taken together all results found here, we may suggest HMGB1 is an important therapeutic target for asthma, once orchestrates the redox signaling, inflammation, and remodeling that contribute to the disease development.

Experimental Asthma Induced By Tropomyosins from Cockroach and Shrimp: Insights into in Vivo Cross-Reactivity

In vivo cross-reactivity among tropomyosins, major pan-allergens among invertebrates, is not established. Our aim was to investigate the effects of purified tropomyosins from cockroach (recombinant Pera7) and shrimp (natural Litv1) on airway inflammation and hyperresponsiveness in a mouse model of asthma. Balb/c mice, 4 to 6 weeks-old, were sensitized twice with 50μg of rPera7 or nLitv1 intraperitoneally with 1 mg alum, and challenged with 50μg of rPer7 or nLitv1 intranasally for three days. A group was sensitized with rPera7 and challenged with nLitv1 under same conditions. Controls received saline on same days. Twenty-four hours after the last challenge, mice were ventilated with FlexiVent®, and in vivo bronchial hyperresponsiveness was evaluated with inhaled methacholine (6.25,12.5,25 and 50mg/ml). After ventilation, bronchoalveolar lavage fluid (BALF) was collected and cell counts were performed. Sensitization and challenge of mice with rPera7 or nLitv1 resulted in increase in bronchial hyperresponsiveness, given by increase in resistance and elastance. Total cells in BALF increased in rPera7 and nLitv1 groups, as compared to controls. There was increase in macrophages (5x104 vs 1x105 and 3x105 for rPera7 and nLitv1, p<0.001) and eosinophils (2x103 vs 1.4x105 and 9.1x105, p<0.001). Mice immunized with rPera7 and challenged with nLitv1 showed no changes in bronchial hyperresponsiveness or cells on BALF as compared to controls. Experimental asthma induced by tropomyosins from cockroach and shrimp mimicked the main characteristics of human asthma. Despite the high degree of sequence identity and IgE immunologic cross-reactivity, our data suggested that in vivo cross-reactivity of these tropomyosins is unlikely.

A half doubling dose change in bronchial hyperresponsiveness in a population represents an important difference.

BackgroundThe prevalence of asthma has increased over recent decades and the reasons for this are poorly understood. A sensitive tool that can evaluate potential risk factors for asthma is bronchial hyperresponsiveness (BHR), a key physiological characteristic of asthma. However, although the minimum clinically important difference in BHR for an individual is accepted to be around one doubling dose, the minimum important change in a population is not defined. As with surrogate measures of cardiovascular disease risk such as blood pressure and cholesterol, a change that is not clinically important in an individual may be extremely important in public health terms.FindingsTo assess the potential impact of a small absolute change in BHR across a population, we modelled the effect of different changes in BHR on the prevalence rates of moderate and severe BHR in an asthmatic population. We calculate that a one half doubling dose increase in BHR increases the prevalence of moderate and severe BHR by 30%. If this was accompanied by an equivalent increase in the population prevalence of moderate and severe asthma, this would be highly significant in public health terms.ConclusionsWe propose that a one half doubling dose worsening in BHR across a population may represent an important change.Electronic supplementary materialThe online version of this article (doi:10.1186/2213-0802-1-4) contains supplementary material, which is available to authorized users.

S118 IL-13 Induced Mouse Airway Inflammation Induces an Increase of Soluble ADAM33 in Bronchoalveolar Lavage Fluid, Which is Enzymatically Active and Associated with Bronchial Hyperresponsiveness

RationaleThe asthma susceptibility gene ADAM33/Adam33 is associated with bronchial hyperresponsiveness(BHR) in humans and mice. Soluble ADAM33 is increased in bronchoalveolar lavagefluid (BALF) of allergic asthma patients (Lee JY et al,...

The effects of natural pollen exposure on inflammatory cytokines and their relationship with nonspecific bronchial hyperresponsiveness in seasonal allergic rhinitis

The exact mechanism of bronchial hyperresponsiveness (BHR) is not clear in allergic rhinitis (AR); an increase of BHR in pollen season suggests that natural pollen exposure causes airway inflammation in seasonal AR (SAR). This study was designed to investigate the effects of natural pollen exposure on inflammatory cytokines and their relationship with BHR. Sixty-six SAR patients with grass pollen sensitivity and 26 nonallergic rhinitis (NAR) patients were included. Peripheral blood samples for cytokine levels were taken and a nonspecific bronchial provocation test was performed during pollen season between May and August. The same measurements were repeated off-season between November and February. These measurements were done in NAR patients once. During the pollen season, SAR patients had significantly more increased levels of IL-13 than NAR patients (11.45 +/- 12.54 versus 5.19 +/- 4.02; p = 0.005). Blood eosinophil numbers were higher in those patients with BHR during pollen season than those without BHR (399.0 +/- 255.8 versus 278.9 +/- 193.2 mm(-3); p = 0.046). Blood eosinophil numbers during off-season were not different in those with and without BHR (respectively, 261.4 +/- 202.3 mm(-3) versus 205.9 +/- 116.9 mm(-3); p = 0.53). IL-10 levels were higher in the patients without BHR (n = 28) than those patients with BHR (n = 22) during off-season (8.12 +/- 13.1 versus 3.28 +/- 0.37; p = 0.04). Having higher levels of IL-10 than threshold value was more frequent in SAR patients without BHR than those patients with BHR during off-season (7/28 versus 1/22; chi(2) = 4.34; p = 0.04). IL-10 has a role in the continuation of BHR during off-season in SAR patients.

Long-Term Effects of Allergen Sensitization and Exposure in Adult Asthma: A Prospective Study

Background We investigated the effects of sensitization and exposure to common domestic allergens on longitudinal changes in lung function and bronchial hyperresponsiveness.Methods Subjects attended 2 visits that were 4 years apart. Skin prick testing was performed and household dust samples were collected for quantification of mite, dog, and cat allergens at baseline. Measurements of lung function, exhaled nitric oxide, and bronchial hyperresponsiveness were completed at both visits.Results Dust samples were collected in 165 of the 200 subjects completing both visits. Mean length of follow-up was 47 months. Bronchial hyperresponsiveness, measured at both visits in 86 subjects, deteriorated in those exposed to high mite allergen levels compared with those not exposed [mean (95% CI) doubling dose change PD20 = -0.44 (-1.07 to 0.19) vs 0.82 (0.27 to 1.36)], but improved in those exposed to high dog allergen levels compared with those not exposed [1.10 (0.33 to 1.86) vs 0.10 (-0.39 to 0.58)]. The associations were significant in the multivariate models. Cat allergen exposure was not associated with any changes in lung function, exhaled nitric oxide, or bronchial hyperresponsiveness.Conclusions In a 4-year prospective cohort of persons with asthma, exposure to high levels of dust mite allergens at baseline was associated with a subsequent increase in bronchial hyperresponsiveness.

The incidence of respiratory symptoms and sensitisation in baker apprentices

The aim of the current study was to describe the incidence of respiratory symptoms and allergic sensitisation and the sequence of events leading to respiratory symptoms among Danish baker apprentices (BA). A total of 114 BA were surveyed over a 20-month period. Questionnaires were completed along with spirometric analysis and skin-prick tests to common and work-related allergens. Bronchial hyperresponsiveness (BHR) was determined at baseline and at the end of the follow-up period. The incidences of work-related rhinitis and asthma-like symptoms were 22.1 and 10.0 cases.100 person-yrs(-1), respectively. At 20 months the cumulative incidence proportion was 40.2 and 20.5% for rhinitis and asthma-like symptoms, respectively. The cumulative incidence of occupational sensitisation was 6.1%. An increased risk of asthma-like symptoms was found in both atopic subjects and in females. In the BA with new onset respiratory symptoms, an increase in BHR from baseline was observed. Forced expiratory volume in one second and forced vital capacity did not change during the follow-up period. No relationship was observed between new sensitisation and new symptoms. In conclusion rhinitis- and asthma-like symptoms were found to develop commonly in Danish baker apprentices. The mechanism by which symptoms arose was perceived to reflect the development of an inflammation rather than the production of a specific immunoglobulin E pathway, as sensitisation to occupational allergens was rarely observed. Hence, respiratory symptoms and allergy may develop through separate pathways.

Asthma, allergy, the athlete and the Olympics

As the 2008 Summer Olympics in Beijing approach, both the general public and health care professionals are gaining interest in the potential health implications of sport. When asthma and allergy are present in athletes, this may affect their performance and achievements and justify the special attention of health care professionals who specialize in taking care of top athletes. However, the impact of allergy and asthma on sport and exercise goes further than just top athletes. The Editors of Allergy decided that in this issue they would focus the attention of allergy and asthma specialists by presenting a series of articles on the relationship between sport, asthma and allergy in the hope that an increased awareness of these problems would be highlighted not only for sports medicine doctors but also for all practicing allergists. Exercise-induced asthma (EIA) is a general concern for growing children and adolescents. In most international guidelines, one of the main objectives of treating asthma during childhood is for the child to be able to master EIA. Also among athletes, and especially elite athletes, EIA and bronchial hyperresponsiveness (BHR) have become major problems with regard to the correct diagnosis and to treatment. EIA is increasingly common among the top athletes of several different types of sport. Traditionally this has been reported mainly in athletes competing in endurance sports in cold climates, especially among crosscountry skiers (1, 2) and swimmers (3, 4), but also among endurance athletes in summer sports (5). A surprisingly high prevalence of asthma (56%) diagnosed by the reversibility of lung function to inhaled s2-agonists (56%) was reported among professional Canadian football players (6). The prevalence of EIA among top athletes has increased over the past decades. Weiler et al. reported 11% prevalence of EIA among American athletes participating in the 1984 Summer Olympic Games (7) and an increase to a prevalence of more than 20% was noticed among American participants in the 1996 Summer Olympic Games in Atlanta (8).

Bronchial Responsiveness During Esophageal Acid Infusion

Among the possible mechanisms explaining the worsening of asthma due to gastroesophageal reflux disease (GERD) is the increase in bronchial hyperresponsiveness. The effects of GERD on bronchial hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The aim of this study was to determine the effects of esophageal acid perfusion on bronchial responsiveness to bradykinin in patients with both asthma and GERD. In 20 patients with asthma and GERD disease, esophageal pH was monitored with a pH meter and bronchial responsiveness was evaluated by aerosol inhalation of bradykinin during esophageal acid perfusion and, 24 h earlier or later the patients were submitted to another bronchial provocation test without acid infusion. No significant changes were observed in FEV(1), FEF(25-75%), FVC, or PEF during acid perfusion. The response to the bronchial provocation test did not differ between the control day and the day of acid infusion (p = 0.61). The concentration provoking a 20% fall in FEV(1) (geometric mean +/- geometric SD) was 1.09 +/- 5.84 on the day of acid infusion and 0.98 +/- 5.52 on the control day. There is no evidence that acid infusion changes bronchial responsiveness to bradykinin. These findings strongly question the significance of acid infusion as a model to study the pathogenesis of GERD-induced asthma.

Changes in bronchial hyperresponsiveness following high‐ and low‐sulphite wine challenges in wine‐sensitive asthmatic patients

Previous studies suggest that challenge of most wine-sensitive asthmatic patients may not result in a reduction in forced expiratory volume in 1 s (FEV(1)). The aim of this study was to assess whether changes in bronchial hyperresponsiveness (BHR) occur following wine challenge of asthmatic patients who report sensitivity to wine, and whether such changes could help clarify the role of sulphite additives in wine-induced asthmatic responses. Eight self-reporting wine-sensitive asthmatic patients completed double-blind challenges with high- and low-sulphite wines on separate days. FEV(1) and histamine PC(20) were measured before and after consumption of 150 mL of wine. None of the eight subjects demonstrated a clinically significant >or=15%) reduction in FEV(1) following challenge with either high- or low-sulphite wine. In contrast, one patient demonstrated clinically significant increase in BHR following challenge with both high- and low-sulphite wines, and a smaller increase in BHR following placebo challenge. A second patient showed a significant increase, while another showed a significant decrease in BHR following challenge with low-sulphite wine. A fourth patient showed borderline increases in BHR following challenge with both high- and low-sulphite wines. Although changes in BHR, in the absence of reductions in FEV(1), were observed in some asthmatic patients following wine challenge, these changes were not consistent with a single aetiology. Consequently, this study did not support a major role for the sulphite additives in wine-induced asthmatic responses in the patients studied. The aetiology of wine-induced asthma is likely to be complex and appears to vary among individuals who are sensitive to these drinks.

Links between allergic rhinitis and asthma

航线的过敏疾病，包括季节的鼻炎，长期的长期的鼻炎和气喘，作为航线 mucosa 的煽动性的混乱被认出，但是在煽动性的反应的地点和疾病的临床的表明不同。气喘和过敏鼻炎经常在一样的病人共存并且被认为分享普通预先安排与环境影响交往的基因因素。两疾病特别地在西洋化的国家在最近的十年在流行增加了。这增加过时的人或物大部分归因于象暴露那样的环境因素到天线污染物质，和早年生活事件，包括到可能影响 IgEproduction 的传染代理人的暴露的度，自从在基因水池的一个重要变化有不够的时间。

Diagnosing asthma in young children

Asthma is defined by the 1997 National Asthma Education and Prevention Program guideline as a chronic inflammatory disorder of the airways which leads to an increase in bronchial hyperresponsiveness to a variety of stimuli or triggers. Since it is difficult to determine whether an individual patient has the above pathophysiology, particularly in young children, it is essential that clinically useful criteria be identified that can serve as proxies for the presence of asthma. There are three reasons for making a diagnosis: to identify the most effective treatment to alleviate symptoms and prevent mortality; to educate the parent or primary caregiver to manage symptoms and avoid triggers; and to estimate the prognosis. A diagnostic test is a procedure which gives a rapid, convenient and inexpensive indication of whether a patient has a certain disease. The likelihood ratio incorporates both the sensitivity and specificity of the test and provides a direct estimate of how much a test result will change the odds of having a disease. By applying the principles of evidence-based medicine to define likelihood ratios for each criterion, it should be possible to define the probability of asthma and to identify the best treatment. Future research should permit accurate correlations to be drawn between the underlying pathophysiology and the clinical condition commonly known as asthma.

β&lt;sub&gt;2&lt;/sub&gt;-Agonists and Bronchial Hyperresponsiveness

Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, and individuals with this disease respond to a range of physiological and chemical insults that are otherwise innocuous to healthy subjects, suggesting that the mechanisms underlying this phenomenon are characteristic of the asthma phenotype. BHR can be increased following exposure to environmental allergens in suitably sensitized individuals, pollutants, and certain viruses and can also be exacerbated by exposure to certain drugs, including nonsteroidal anti-inflammatory agents and beta-blockers. Although beta2-agonists administered acutely remain the treatment for the symptoms of asthma, paradoxically, regular treatment with these drugs can result in an increase in BHR, and this has been suggested to contribute to the increase in asthma morbidity and mortality that has been reported by numerous investigators. This article highlights our current understanding of this phenomenon and examines the potential mechanisms responsible for this effect.

What is New with the β2-Agonists: Issues in the Management of Asthma

To review the more recent literature addressing the issue of whether beta2-agonists can worsen asthma and/or increase the risk of severe exacerbations and death from asthma. PubMed was searched (2001-December 2004), along with the Food and Drug Administration and Cochrane Library Web sites. In addition, the bibliographies of recent reviews of the subject were assessed. Randomized clinical trials, retrospective and prospective cohort studies, and meta-analyses published in the past 3 years were reviewed. Studies assessing the potential for beta2-agonists to worsen outcomes in asthma as well as long-term studies assessing asthma outcomes that included an arm with regular administration of short- or long-acting inhaled beta2-agonists (LABAs) were selected. Worsening asthma was defined as a decline in lung function, an increase in bronchial hyperresponsiveness, exacerbations, or death. Studies older than 3 years selected from the bibliographies of the primary articles that addressed background perspective were also included where appropriate. The studies fell into 3 primary categories with some overlap: those assessing toxicity of the S-enantiomer of albuterol, those evaluating the risk of specific genotypes regarding worsening asthma, and those assessing asthma outcomes with LABA therapy. The current data on the use of beta2-agonists continue to support the national and international guidelines for the treatment of asthma. That is, short-acting inhaled beta2-agonists should only be used as needed for symptoms and prevention of exercise-induced bronchospasm, and LABAs should only be used regularly as adjunctive therapy with inhaled corticosteroids in patients whose asthma is not controlled with low to medium doses of the inhaled corticosteroid.

The World Trade Center Residents’ Respiratory Health Study: New-Onset Respiratory Symptoms and Pulmonary Function

The destruction of the World Trade Center (WTC) on 11 September 2001 in New York City resulted in the massive release of pulverized dust and combustion products. The dust and smoke settled in the surrounding area, which encompassed a large residential community. We hypothesized that previously normal residents in the community surrounding the former WTC would have an increased incidence of persistent respiratory symptoms and abnormalities in screening spirometry. A hybrid cross-sectional and retrospective cohort study using a symptom-based questionnaire and onsite screening spirometry in residents in an exposed area and in a control area was performed 12 ± 4 months after the collapse. Surveys were analyzed from 2,812 residents. New-onset respiratory symptoms were described by 55.8% of residents in the exposed area, compared with 20.1% in the control area after the event. Persistent new-onset symptoms were identified in 26.4 versus 7.5% of residents in the exposed area versus control area, respectively. No differences in screening spirometry between the groups were detected. A small pilot study suggested the possibility of an increase in bronchial hyperresponsiveness in exposed participants with persistent symptoms. The data demonstrate an increased rate of new-onset and persistent respiratory health effects in residents near the former WTC compared with a control population.

Effect of intranasal triamcinolone acetonide on bronchial hyper-responsiveness in children with seasonal allergic rhinitis and comparison of perceptional nasal obstruction with acoustic rhinometric assessment

Objective: Many patients with allergic rhinitis (AR) have bronchial hyper-responsiveness (BHR), and seasonal variation of BHR has been demonstrated in these patients. We aimed to investigate how BHR in children with seasonal AR is modified by triamcinolone acetonide aqueous nasal spray (TANS) therapy during the pollen season. A secondary aim was to assess the efficacy of TANS on nasal congestion by acoustic rhinometry and symptom scores. Methods: A total of 34 children aged 7–18 years with grass pollen-induced AR and 18 age and sex-matched healthy controls were included in study. The patients were divided into the following two subgroups: 22 patients who had AR only; and 12 patients who had AR and asthma. All of them had a baseline BHR (PC 20FEV 1 methacholine <8 mg/ml). All patients received 220 μg TANS once daily for 4 weeks following a 1-week run-in period. Nasal patency was measured by acoustic rhinometry and patients recorded their nasal obstruction scores in a diary. Results: There was no significant difference at baseline pulmonary function test parameters between the patients and the healthy control children. None of the control subjects had BHR. Asthmatic children with AR had significantly reduced baseline PC 20FEV 1 when compared with the AR only group [mean±S.E.M., (1.60±0.57 mg/ml versus 2.93±0.42 mg/ml, P=0.021)]. The mean PC 20FEV 1 values increased slightly at the end of treatment in both group (from 1.60±0.57 mg/ml to 3.25±1.11 and from 2.93±0.42 mg/ml to 3.93±1.41 mg/ml), but the change was not statistically significant. TANS produced substantial symptomatic recovery in nasal obstruction according to patients’ daily diary assessments, and significantly improved all objective acoustic rhinometry parameters. Conclusions: Once-daily intranasal TANS 220 μg effectively controlled nasal obstruction in children with seasonal AR according to subjective and objective assessments, and blocked the increase in BHR to methacholine after high-load natural pollen exposure. There was no correlation between patients’ own subjective assessment of nasal obstruction and objective acoustic rhinometric assessment.

Asthma and allergy: a worldwide problem of meanings and management?

Asthma and allergy: a worldwide problem of meanings and management?

Increased resting bronchial tone in normal subjects acclimatised to altitude

Background: Normal subjects frequently experience troublesome respiratory symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and full and partial flow-volume loops were measured before and after ascent to 5000 m...