Increase In Bronchial Hyperreactivity Research Articles

Military small arms fire in association with acute decrements in lung function

ObjectiveAfter introduction of unleaded ammunition, Norwegian Armed Forces received reports of acute respiratory symptoms in soldiers after exposure to fumes from firing the standard weapon, HK416. The aim of the...

Inflammatory markers as exacerbation risk factors after asthma therapy switch from inhaled steroids to montelukast

BackgroundAsthma guidelines allow anti-leukotriene medications to be used as an alternative to inhaled corticosteroids (ICS) in second-step intensity therapy. The aim of the study was to analyze the risk factors of exacerbations, particularly inflammatory markers, during the 12-month period following therapy reduction from an ICS to montelukast in young patients with mild asthma. MethodsA total of 84 patients (aged 7–18 years old) with mild asthma controlled by low-dose ICS, had their treatment switched to montelukast. Exhaled nitric oxide (eNO), sputum eosinophils (sEos), and bronchial hyperreactivity (BHR) were assessed at the beginning and then every three months throughout the one-year period. The patients with asthma exacerbations (first severe or third mild) were discontinued from the study. ResultsOver the study period, 22 patients (26%) discontinued montelukast due to asthma exacerbations. An increased risk of exacerbations was noted among patients with initial sEos above 2.5% (relative risk, RR 36.6; 95% CI: 7.1–189.3; p < 0.001), as well as those with augmented BHR (RR 9.5; 2.8–31.6; p < 0.001), or eNO greater than 20 ppb (RR 3.7; 95% CI: 1.3–10.7; p = 0.013). An increase in BHR and eNO was observed during the last visit before exclusion. ConclusionsAfter switching treatment from a low-dose ICS, montelukast maintained control of asthma symptoms in 75% of patients. High sEos before the treatment change was the strongest exacerbation risk factor. In patients with asthma controlled by low-dose ICS and low inflammatory markers, treatment could be safely switched to montelukast.

Asthme et obésité, effets synergiques

Asthma and obesity are associated in epidemiological studies and both share a genetic susceptibility. Obesity is a risk factor for uncontrolled asthma because of many associated co-morbidities like obstrucive sleep apnoea, gastro-oesophageal reflux and bronchial hyperreactivity related to changes in ventilatory mechanics. Moreover, adipose tissue inflammation caused by obesity leads to eosinophil recruitment, their activation in the bronchial wall and an increase in bronchial hyperreactivity. Asthma may be pejorative for the evolution of obesity because of corticosteroid treatment and physical inactivity, but no evidence for this has yet been shown. Treatment of obesity by regular physical activity and weight loss, has been shown to improve asthma symptoms in many studies. This should encourage the use of dietetic measures and exercise in the management of asthma.

Early impact of smoking on lung function, health, and well‐being in adolescents

Smoking is the single most important risk factor for the development of chronic obstructive pulmonary disease, and more than 80% of adult smokers started smoking before the age of 20. The aim of our study was to evaluate the early impact of smoking on lung function, health, and well-being in adolescents. Twenty-four non-smokers (10 male, 14 female, mean age 17.6 years) and 24 smokers (mean of 3.5 pack-years; 15 male, 9 female, mean age 17.8 years) were compared in terms of lung function, bronchial hyperreactivity (BHR), levels of exhaled carbon monoxide (eCO), exhaled nitric oxide (eNO), and blood counts. A questionnaire containing items from the ISAAC study was used to detect differences in health and well-being. There were no significant differences in lung function values between non-smokers and smokers (VC 95% vs. 103%, FEV(1) 106% vs. 116%, FEV(1) %/VC MAX 94.6% vs. 95.2%), whereas BHR significantly differed (P < 0.05). Furthermore, significant differences were found for eCO, eNO, Hb, leukocytes, and neutrophils. Health and well-being in terms of sleep and physical activity were significantly worse in smokers. Our results suggest an early impact of smoking on health after as few as 3.5 pack-years. Early signs of smoking are an increase in BHR, changes in blood count and a decrease of eNO even before changes in lung function become apparent.

Perimenstrual increase in bronchial hyperreactivity in premenopausal women: Results from the population-based SAPALDIA 2 cohort

Studies on perimenstrual asthma are inconsistent, and different methodologies limit comparisons. To investigate cyclic variations in bronchial hyperreactivity (BHR) to methacholine in premenopausal women in a population-based cohort and assess effect modification by oral contraceptives (OCs). Day of menstruation cycle at the time of methacholine challenge was calculated in 571 menstruating women without hormonal treatment, age 28 to 58 years, on the basis of questionnaire data from the Swiss cohort study on Air Pollution And Lung Disease In Adults (SAPALDIA) cohort 2001/2002. A window of risk was defined 3 days before and after the first day of menstruation. Logistic and linear regression analyses were performed adjusting for main predictors of BHR and stratifying for asthma status. The impact of OCs was studied in the same sample enlarged by 130 women taking OCs. The prevalence of BHR was 13% (fall of > or =20% in FEV(1) up to a maximal cumulative dose of 2 mg), and 6% had asthma. A total of 143 women had undergone methacholine challenge within the risk window. We observed a significant increase in BHR within the window of risk (odds ratio [OR], 2.3; 95% CI, 1.27-4.29). A cyclic association pattern was confirmed by trigonometric functions. Effect modification by asthma status and oral contraceptive use was found, with lower OR in subjects without asthma and OR <1 in women using OCs. The data provide evidence of a systematic variation in BHR during the menstruation cycle, supporting the hypothesis of a hormonal influence. OCs appear to have a protective effect. Cyclicity of BHR could be of clinical importance in view of future medication recommendations and timing of respiratory function tests in women.

Withdrawal of inhaled steroids in children with non-cystic fibrosis bronchiectasis

To study the effects of inhaled steroid withdrawal on bronchial hyperreactivity, sputum inflammatory markers and neutrophilic apoptosis in children with non-cystic fibrosis (non-CF) bronchiectasis. To evaluate the role of inhaled steroids in the treatment of children with non-CF bronchiectasis with specific emphasis on the bronchial hyperreactivity and neutrophilic apoptosis. Twenty-seven children with steady-state non-CF bronchiectasis were evaluated primarily with metacholine challenge tests and apoptotic neutrophil ratios in induced sputum and secondarily with symptom scores, pulmonary function tests and tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) levels and neutrophil ratios in induced sputum before and after 12-week withdrawal of inhaled steroids. There were 16 girls and 11 boys. Median (interquartile range) age was 11.4 (9.5-13.6) years, follow-up duration was 3.5 (2-6.5) years. Symptom scores (4 vs. 3; P = 0.27), oxygen saturation (95% vs. 97%; P = 0.06), pulmonary function tests (FEV1: 82% predicted vs. 83% predicted; P = 0.73), sputum neutrophil ratios (29.9% vs. 46.8%; P = 0.20), TNF-alpha (58 pg/mL vs. 44.5 pg/mL; P = 0.55) and IL-8 (2.7 ng/mL vs. 2.4 ng/mL; P = 0.82) levels in induced sputum were similar before and after 12-week withdrawal of inhaled steroids. However, the number of patients with bronchial hyperreactivity increased (37% vs. 63% of patients; P = 0.016) and neutrophilic apoptosis in induced sputum decreased (42.8% vs. 20.2%; P = 0.03) after withdrawal. In this study, 12 week-withdrawal of inhaled steroid treatment resulted in a significant increase in bronchial hyperreactivity and decrease in neutrophil apoptosis, but no change in sputum inflammatory markers in children with non-CF bronchiectasis was observed.

The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.

House Dust Mite Facilitates Ovalbumin-specific Allergic Sensitization and Airway Inflammation

Mouse models of allergic airway disease have greatly contributed to our understanding of disease induction and pathogenesis. Although these models typically investigate responses to a single antigen or allergen, humans are frequently exposed to a myriad of allergens, each with distinct antigenic potential. Given that airway exposure to ovalbumin (OVA), a prototypic innocuous antigen, induces inhalation tolerance, we wished to investigate how this response would be altered if OVA were encountered concurrently with a house dust mite extract (HDM), which we have recently shown is capable of eliciting a robust allergic airway inflammatory response that is mediated, at least in part, by granulocyte-macrophage colony-stimulating factor. Balb/c mice were exposed daily to HDM (intranasally) followed immediately by exposure to aerosolized OVA for 5 weeks. To allow the inflammatory response elicited by HDM to subside fully, mice were then allowed to rest, unexposed, for 8 weeks, at which time they were rechallenged with aerosolized OVA for 3 consecutive days. At this time, we observed a robust eosinophilic inflammatory response in the lung that was associated with an increase in bronchial hyperreactivity. Moreover, we documented significantly elevated serum levels of OVA-specific IgE and IgG(1) and increased production of the Th2 cytokines interleukin 4 (IL-4), IL-5, and IL-13 by splenocytes stimulated in vitro with OVA. Our data demonstrate the potential of a potent allergen such as HDM to establish a lung microenvironment that fosters the development of allergic sensitization to otherwise weak or innocuous antigens, such as OVA.

Introducción

Asthma is the most frequent chronic disease in childhood. Its prevalence varies (in Spain between 12 % in coastal regions and 6 % in the Castilian plateau). Asthma represents chronic inflammation of the airways associated with an increase in bronchial reactivity to various stimuli, leading to reduced air flow and subsequent remodeling of the bronchial wall. Asthma usually begins in the first few years of life and 30 % of patients will continue to be asthmatic throughout their lives. The main characteristic associated with the persistence of asthma in adulthood seems to be allergy. Another risk factor is the presence of bronchial hyperreactivity. Wheezing associated with viral infections in childhood shows a favorable outcome when not associated with atopic features. The atopic disposition is caused by the interaction between genetic and distinct environmental factors (allergens), as well as by the various clinical manifestations that favor a mainly Th2 response, with interleukins that lead to the formation of specific IgE, pro-inflammatory cytokines, bronchial hyperreactivity, etc. In most cases, asthma is mainly an allergic process, mediated by an IgE mechanism. Inhalation of allergens is considered the most important cause of the onset of asthma in predisposed children. First the presence of an allergen gives rise to sensitization, with the formation of specific IgE. In a subsequent contact, mediators are released, with inflammatory response of the airways and an increase in bronchial hyperreactivity. If the presence of the allergen is prolonged, inflammation and subsequent healing may lead to irreversible damage to the bronchial wall and permanent deterioration of respiratory function. In children with asthma, the aim is to modify the natural history of the disease and prevent its persistence in adulthood. This involves identifying the allergen or allergens causing the symptoms, confirming the role of these allergens in clinical manifestations through specific challenge tests and, lastly, indicating the treatment be followed.

Nebivolol (Nebilet®) - ein sicherer Betablocker der dritten Generation - auch für Patienten mit obstruktiven Lungenerkrankungen?

Twenty-four patients with bronchial hyperreactivity due to asthma (8 patients), COPD (13) and of unknown origin (3) entered and completed a randomized double-blind intraindividual cross-over study. Thirteen patients first received the highly selective vasodilatating beta 1-blocker Nebivolol (5 mg) and 11 patients first placebo with a wash-out period of at least 2 days. Before the controlled oral intake of the tablets, the patients were challenged with increasing inhalative doses of carbachol between 8 and 9 a.m. according to the recommendation of the German Society of Pneumology. At 10, 11 and 12 a.m. and 1 and 2 p.m. control measurements of airway patency (Raw, FEV1) were performed in the body box. At the same time intervals, oxygen saturation and pulse rate (pulsoximetry) including systolic and diastolic blood pressure were monitored. From 2-3 p.m. the carbachol provocation was repeated as in the morning to assess the changes in hyperreactivity due to Nebivolol. During the Nebivolol phase, blood pressure values and pulse rates were significantly reduced compared to the placebo phase. At the same time intervals, no significant changes of the measured body box variables to assess airway obstruction were observed during therapy with Nebivolol compared to placebo. Comparing the measured variables (maximal deviation from base-line values of Raw and FEV1) during carbachol provocation in the afternoon under Nebivolol and placebo with the values in the morning before any medication (base-line values), there were also no significant detectable differences indicating an increase of bronchial hyperreactivity under Nebivolol treatment. It seems that Nebivolol in these hyperreactive patients is as safe as placebo despite its significant effect on blood pressure and pulse rate.

Passive cigarette smoke—challenge studies: Increase in bronchial hyperreactivity

Degree and duration of bronchial hyperreactivity (BHR) after environmental tobacco smoke (ETS) inhalation was assessed in 31 smoke-sensitive subjects with asthma who exhibited lower airway symptoms on ETS exposure (group I) and 39 smoke-sensitive subjects without asthma who manifested only upper airway symptoms on cigarette-smoke exposure (group II). Subjects were challenged with ETS for 4 hours in a static-test chamber. The atmosphere was continuously monitored for airborne particulate levels (800 cpm), total suspended particulates (1266 ± 283 μg/m 3), and airborne nicotine levels (226 ± 49 μg/m 2). Methacholine challenges were performed before and serially after cigarette-smoke exposure, and the provocative dose causing a 20% fall in FEV 1 was determined. Five of the 31 smoke-sensitive subjects with asthma and none of the smoke-sensitive subjects without asthma reacted to cigarette-smoke challenge (≥20% fall from baseline FEV 1). Thirty-two percent ( 10 31 ) of the subjects with asthma demonstrated increased BHR at 6 hours, 29% ( 9 31 ) at 24 hours, and 13% ( 4 31 ) up to day 14 after ETS challenge. Of the subjects without asthma, 18% ( 7 39 ) demonstrated increased BHR at 6 hours, 10% ( 4 39 ) at 24 hours, and 8% ( 3 39 ) at 3 weeks. These studies demonstrated an increase in BHR after cigarette-smoke challenge in a number of study subjects (although they were clinically asymptomatic) and suggest that prolonged subclinical airway inflammation can occur in the absence of demonstrable change in airway caliber on exposure to ETS.

Bronchial Response to Methacholine in “Healthy” Children of Asthmatic Parents: Effect of Treatment with Cromolyn Sodium

Cumulative dose response curves to inhaled methacholine were established in 24 "healthy" children of asthmatic parents and 7 healthy children of healthy parents. Atopic children of asthmatic parents demonstrated higher bronchial hyperreactivity (BHR) than nonatopic children. The BHR was about ten times less than in the atopic parents of asthmatic children, indicating marked increase in BHR with age in atopic members of asthmatic families. Six weeks of treatment with cromolyn sodium (disodium cromoglycate) decreased BHR significantly (p less than 0.05) in eight atopic children, while no change occurred in BHR in five nonatopic children.

Cromolyn sodium: a review of mechanisms and clinical use in asthma.

The cellular and clinical pharmacology of cromolyn sodium are reviewed. Cromolyn sodium inhibits the release of mediators of inflammation, induced by specific antigens as well as nonspecific mechanisms, such as exercise, from mast cells. Cromolyn may also inhibit the activity of other cell types that produce inflammation. It is the only antiasthmatic that blocks both early and late asthmatic responses induced by allergen inhalation and exercise. Consequently, cromolyn therapy can block the increase in bronchial hyperreactivity induced by chronic allergen exposure. Cromolyn is effective for controlling the symptoms of mild to moderate chronic asthma in 60 to 70 percent of patients. In comparative studies, cromolyn has been as effective as theophylline for controlling symptoms of chronic asthma with fewer side effects, and may be particularly suited for asthmatic patients with learning or behavioral problems. The combination of theophylline and cromolyn is often more effective than either agent alone. Because of the convenience of administration, cromolyn is preferred over theophylline for exercise-induced asthma. Cromolyn may allow the corticosteroid dosage to be reduced in severe steroid-dependent asthmatics, but it is primarily indicated for the prophylaxis of mild to moderate disease. Adverse reactions to cromolyn are uncommon to rare. Cromolyn is now available in a Spinhaler, a metered-dose aerosol, and a nebulizer solution. If taken properly all preparations appear to be equally effective. Attention to proper inhalation technique and appropriate education of the patient is essential to ensure a good outcome with cromolyn.