Predictor Factors for Airway Responsiveness during Bronchial Allergen Challenge Tests: Role of Allergen-Specific IgE Levels, Cutaneous Allergen Sensitivity and Non-Specific Airway Hyperresponsiveness

2009 ◽  
Vol 123 (2) ◽  
pp. S9-S9
Author(s):  
C. Barnig ◽  
A. Purohit ◽  
A. Casset ◽  
C. Sohy ◽  
F. Lieutier-Colas ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Allergen Challenge ◽  
Specific Ige ◽  
Airway Responsiveness ◽  
Challenge Tests ◽  
Bronchial Allergen Challenge ◽  
Predictor Factors

scholarly journals Allergen Induced Increase in Nonallergic Airway Responsiveness: A Citation Classic Revisited

2000 ◽  
Vol 7 (2) ◽  
pp. 182-187 ◽  
Author(s):  
Donald W Cockcroft
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Immunoglobulin E ◽  
Allergen Challenge ◽  
Airway Responsiveness ◽  
Forced Expiration ◽  
Citation Classic ◽  
Poor Understanding ◽  
The Times

BACKGROUND:The present paper revisits the 1977 paper by DW Cockcroft, RE Ruffin, the late J Dolovich and FE Hargreave entitled "Allergen-induced increase in nonallergic bronchial reactivity" (Clin Allergy1977;7:503-13) that became a citation classic. Although clinical types of asthma were recognized at the time, there was a poor understanding regarding the role of allergic reactions in causing increases in airway hyperresponsiveness. The objective was to study formally Dr Altounyan's observation that patients with asthma showed increases in airway responsiveness at the times of natural allergen exposure during pollen season. Thirteen atopic patients with asthma were studied over two days, following inhalation of diluent (control) and following doubling amounts of an allergen solution at 10-min intervals until forced expiration volume in 1 s fell by 20%. Methacholine and histamine challenges were performed before, at 8 h, at 32 h and seven days following the inhalations. A significant reduction (reduction of at least one doubling concentration) in the provocative concentration that causes a 20% fall in forced expiration volume in 1 s occurred in seven of 13 patients, and more often in subjects with a late bronchoconstrictor response to allergen challenge.IMPORTANCE:The study showed that large changes in airway responsiveness could occur in patients with asthma and suggested that allergens could cause, rather than trigger, asthma. The study also led to the concept of asthma inducers and inciters -- inducers causing airway inflammation and inciters provoking bronchospasm. The results led to a series of observations that have now implicated immunoglobulin E-mediated airway inflammation as perhaps the most important cause of airway hyperresponsiveness in asthma.

Effects of IL-13 on airway responses in the guinea pig

2002 ◽  
Vol 282 (1) ◽  
pp. L44-L49 ◽  
Author(s):  
Brian Morse ◽  
Joseph P. Sypek ◽  
Debra D. Donaldson ◽  
Kathleen J. Haley ◽  
Craig M. Lilly
Keyword(s):  
Guinea Pig ◽  
Airway Hyperresponsiveness ◽  
Histological Grade ◽  
Allergen Challenge ◽  
Cell Counts ◽  
Respiratory System Resistance ◽  
Airway Responses ◽  
Necessary And Sufficient ◽  
Eosinophil Accumulation

Levels of interleukin (IL)-13 are increased in asthmatic airways. IL-13 has been shown to be necessary and sufficient for allergen-induced airway hyperresponsiveness and increased inflammatory cell counts in bronchoalveolar lavage (BAL) fluid in a murine model of asthma but is thought to protect against airway inflammation when low doses are provided to the guinea pig lung. To determine the role of IL-13 in the guinea pig, we studied the effects of a 360-μg/kg dose of nebulized IL-13 in naive animals and of IL-13 abrogation after airway challenge of sensitized animals. Nebulized IL-13 significantly decreased the dose of histamine required to double baseline respiratory system resistance (ED100, 22 ± 3 vs. 13 ± 2 nmol/kg; P < 0.05) and was associated with recovery of significantly greater numbers of macrophages, lymphocytes, eosinophils, and neutrophils in BAL fluid. Guinea pigs pretreated with a fusion protein that binds IL-13 [soluble IL-13 receptor α2 (sIL-13Rα2)] were protected from developing antigen-induced airway hyperresponsiveness (ED100, 210 ± 50 vs. 20 ± 10 nmol/kg; P <0.01). sIL-13Rα2 (2 doses of 20 mg/kg) significantly reduced the histological grade of allergen-induced lung eosinophil accumulation, whereas the effects of two doses of 10 mg/kg were not significant. These findings demonstrate that the tissue levels of IL-13 induced by allergen challenge of sensitized animals induce airway hyperresponsiveness and inflammation and that IL-13 is required for the expression of allergen-induced airway hyperresponsiveness in the guinea pig ovalbumin model.

Allergen-induced airway hyperresponsiveness in Brown-Norway rat: role of parasympathetic mechanisms

1993 ◽  
Vol 75 (1) ◽  
pp. 279-284 ◽  
Author(s):  
W. Elwood ◽  
T. Sakamoto ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Airway Hyperresponsiveness ◽  
Allergen Challenge ◽  
Electrical Field Stimulation ◽  
Airway Responsiveness ◽  
Brown Norway ◽  
Field Stimulation ◽  
Electrical Field ◽  
Norway Rat

Enhanced parasympathetic mechanisms may contribute to airway hyperresponsiveness. The present study examined whether the in vivo increase in airway responsiveness seen 18–24 h after either a single or chronic aerosolized allergen challenge protocol in actively sensitized Brown-Norway rats was due to altered parasympathetic mechanisms. The roles of central and reflex vagal mechanisms were studied by performing bilateral cervical vagotomy before measurement of airway responsiveness. Bilateral vagotomy failed to reduce the increase in airway responsiveness after either a single or chronic allergen challenge. The roles of increased neural release of acetylcholine (ACh) and increased end organ responsiveness were studied in vitro. The isometric responses of tracheal and bronchial strips to both electrical field stimulation and exogenously applied ACh from rats exposed both to single and chronic allergen challenges were compared with those from saline-exposed rats. The responses to electrical field stimulation and to exogenous ACh were not significantly enhanced 18–24 h after either protocol. We conclude that the airway hyperresponsiveness observed in this allergic rat model is not mediated through an enhancement of parasympathetic mechanisms.

scholarly journals Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma

1999 ◽  
Vol 189 (10) ◽  
pp. 1621-1630 ◽  
Author(s):  
George T. De Sanctis ◽  
James A. MacLean ◽  
Kaoru Hamada ◽  
Sanjay Mehta ◽  
Jeremy A. Scott ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Allergic Asthma ◽  
Airway Hyperresponsiveness ◽  
Airway Responsiveness ◽  
Wild Type ◽  
Methacholine Challenge ◽  
Oxide Synthase ◽  
Nos Isoforms ◽  
Deficient Mice

Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.

Protective Effect of a New Anti-Asthmatic Agent (Minocromil) in Bronchial Allergen Challenge Tests

Allergy ◽  
1985 ◽  
Vol 40 (6) ◽  
pp. 458-460
Author(s):  
U. G. Svendsen ◽  
L. Frølund ◽  
F. Madsen ◽  
B. Weeke
Keyword(s):  
Protective Effect ◽  
Allergen Challenge ◽  
Challenge Tests ◽  
Bronchial Allergen Challenge

Ozone-induced airway hyperresponsiveness: role of superoxide anions, NEP, and BK receptors

1995 ◽  
Vol 78 (3) ◽  
pp. 1015-1022 ◽  
Author(s):  
H. Tsukagoshi ◽  
E. B. Haddad ◽  
J. Sun ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Airway Hyperresponsiveness ◽  
Lavage Fluid ◽  
Airway Responsiveness ◽  
Ozone Exposure ◽  
Brown Norway ◽  
Superoxide Anions ◽  
Norway Rat

We investigated the role of reactive oxygen species in ozone-induced airway hyperresponsiveness (AHR) in Brown Norway rats. Airway responsiveness to inhaled acetylcholine (ACh) and bradykinin (BK) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were measured in vivo. Neutral endopeptidase (NEP) activity assay and measurement of BK-receptor binding sites in Brown Norway rat lungs were carried out in vitro. Apocynin (5 mg/kg), an inhibitor of superoxide anion-generating NADPH oxidase, was administered perorally 30 min before a 3- or 6-h exposure to 3 ppm of ozone, and the animals were studied 18–24 h postexposure. Ozone induced increases in airway responsiveness to ACh and BK and in neutrophil counts in BALF. Apocynin inhibited the increase in airway responsiveness to BK but not to ACh without affecting the neutrophil counts in BALF. The antioxidants allopurinol and deferoxamine prevented ozone-induced AHR to both ACh and BK but did not reduce neutrophil counts. To further examine the mechanisms of ozone-induced AHR to BK, we measured NEP activity and the density of BK receptors in vitro after ozone exposure. Ozone exposure had no significant effect either on NEP activity or on the affinity and the number of BK receptors in lungs from rats treated with or without apocynin. We conclude that superoxide anions released from inflammatory cells in the airway may be involved in ozone-induced AHR. Inactivation of NEP or upregulation of BK receptors do not appear to be involved, but the possibility of localized changes cannot be excluded.

Mechanisms of airway smooth muscle relaxation during maturation

2005 ◽  
Vol 83 (10) ◽  
pp. 833-840 ◽  
Author(s):  
Lu Wang ◽  
Thomas M Murphy ◽  
Pasquale Chitano
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Relaxation ◽  
Electrical Field Stimulation ◽  
Airway Responsiveness ◽  
Smooth Muscle Relaxation ◽  
Asthma Prevalence ◽  
Spontaneous Relaxation

Greater airway responsiveness in healthy juveniles is considered a factor in the higher asthma prevalence at a young age compared with adults. We have developed a guinea pig maturational model that utilizes tracheal strips from 1-week-, 3-week-, and 3-month-old guinea pigs to study the role of airway smooth muscle (ASM) in juvenile airway hyperresponsiveness. Because a reduced ability of ASM to spontaneously relax may contribute to airway hyperresponsiveness by maintaining bronchospasm and thus high airway resistance, we have employed this model to study ASM spontaneous relaxation during electrical field stimulation (EFS). Since relaxation during EFS had been neither described nor quantified during maturation, we developed new indices that allowed an appropriate comparison of the relaxing response from strips of different age animals. Using these indices we found that, whereas strips from adult animals relax to a level of tension similar to that found in the absence of stimulation, this ability to spontaneously relax is essentially absent in trachealis from infant animals. These results confirmed that maturation of ASM relaxation may play a role in juvenile airway hyperresponsiveness and that our maturational model is suitable to study the mechanisms regulating spontaneous relaxation in physiological conditions. We investigated the role of prostanoids in ASM relaxation and showed that cyclooxygenase inhibition increases relaxation in infant ASM to levels similar to adults. These results suggest that prostanoids regulate the ability of ASM to spontaneously relax, i.e., they reduce relaxation. We have produced preliminary data suggesting a maturational change in the level of prostanoids. Moreover, the possible action of acetylcholinesterase on maturation of ASM relaxation is discussed here on the basis of a preliminary study. We suggest that impairment of ASM relaxation likely contributes to increased airway responsiveness.Key words: acetylcholinesterase, airway responsiveness, asthma, ontogenesis, prostanoids.

scholarly journals Tidal stretches do not modulate responsiveness of intact airways in vitro

2010 ◽  
Vol 109 (2) ◽  
pp. 295-304 ◽  
Author(s):  
Adam S. LaPrad ◽  
Thomas L. Szabo ◽  
Béla Suki ◽  
Kenneth R. Lutchen
Keyword(s):  
Smooth Muscle ◽  
Ultrasound Imaging ◽  
Airway Hyperresponsiveness ◽  
Breathing Pattern ◽  
Airway Responsiveness ◽  
Integrated System ◽  
Airway Constriction ◽  
Static Conditions

Studies on isolated tracheal airway smooth muscle (ASM) strips have shown that length/force fluctuations, similar to those likely occurring during breathing, will mitigate ASM contractility. These studies conjecture that, solely by reducing length oscillations on a healthy, intact airway, one can create airway hyperresponsiveness, but this has never been explicitly tested. The intact airway has additional complexities of geometry and structure that may impact its relevance to isolated ASM strips. We examined the role of transmural pressure (Ptm) fluctuations of physiological amplitudes on the responsiveness of an intact airway. We developed an integrated system utilizing ultrasound imaging to provide real-time measurements of luminal radius and wall thickness over the full length of an intact airway ( generation 10 and below) during Ptm oscillations. First, airway constriction dynamics to cumulative acetylcholine (ACh) doses (10−7 to 10−3 M) were measured during static and dynamic Ptm protocols. Regardless of the breathing pattern, the Ptm oscillation protocols were ineffective in reducing the net level of constriction for any ACh dose, compared with the static control ( P = 0.225–0.793). Next, Ptm oscillations of increasing peak-to-peak amplitude were applied subsequent to constricting intact airways under static conditions (5.0-cmH2O Ptm) with a moderate ACh dose (10−5 M). Peak-to-peak Ptm oscillations ≤5.0 cmH2O resulted in no statistically significant bronchodilatory response ( P = 0.429 and 0.490). Larger oscillations (10 cmH2O, peak to peak) produced modest dilation of 4.3% ( P = 0.009). The lack of modulation of airway responsiveness by Ptm oscillations in intact, healthy airways suggests that ASM level mechanisms alone may not be the sole determinant of airway responsiveness.

scholarly journals Delayed Asthmatic Response to Allergen Challenge and Cytokines Released by Nonspecifically Stimulated Blood Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Zdenek Pelikan
Keyword(s):  
Blood Cells ◽  
Allergen Challenge ◽  
Th1 Cells ◽  
Asthmatic Response ◽  
Asthma Patients ◽  
Additional Role ◽  
Bronchial Allergen Challenge ◽  
Support Evidence

Background. Bronchial asthma patients can develop various asthmatic response types following bronchial allergen challenge, such as immediate (IAR), late (LAR), dual late (DLAR), or delayed (DYAR), due to different immunologic mechanisms. The DYAR, recorded in 24 patients, beginning between 26 and 32 hrs and lasting up to 56 hrs after the bronchial allergen challenge, differs from the IAR, LAR, and DLAR in clinical, diagnostic, and immunologic aspects. Objective. To investigate amounts of particular cytokines released by the blood cells after an additional nonspecific stimulation with Phorbol 12-myristate 13-acetate (PMA) during the DYAR. Methods. In 24 patients, the repeated DYAR was supplemented with determination of cytokines both in the nonstimulated plasma and in the supernatants of the blood cells stimulated with PMA before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results. No significant changes of the prechallenge cytokine concentrations in the non-stimulated serum were recorded in the DYAR patients as compared with the healthy subjects. The DYAR was accompanied by significantly increased postchallenge concentrations (P<0.05) of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, G-CSF, TNF-α, and TGF-β, while decreased concentration of IL-7 (P<0.05) in the nonstimulated plasma. The significantly increased postchallenge concentrations of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, TNF-α, and TGF-β were released by peripheral blood cells after stimulation with PMA, as compared with both their prechallenge concentrations and with the PBS control values. Conclusions. These results would support evidence for an important role of the Th1 cells, neutrophils, monocytes, and probably also NK cells in the immunologic mechanism(s) leading to the development of the clinical DYAR. Nevertheless, an additional role of macrophages, endothelial and epithelial cells in these mechanisms cannot be even excluded.

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