Reduced late asthmatic response by repeated low-dose allergen exposure

Palmqvist, Mona; Cui, ZH; Sjöstrand, Margareta; Lindén, Anders; Lötvall, Jan

doi:10.1183/09031936.01.17508720

Cited by 19 publications

(18 citation statements)

References 36 publications

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“…In previous repeated low-dose allergen challenge studies, ICS-naïve asthmatics demonstrated small reductions in FEV1 immediately after allergen exposure (ranging from 6.50 to 9.2%) without any significant effect on FEV1 measured the next morning [16][17][18][25][26][27][28][29]; this is similar to our findings. However, these previous studies also demonstrated increased airway inflammation; FeNO, sputum measurements of eosinophils and sputum Th2 mediators increased after low-dose challenge [18,27,28].…”

Section: Discussionsupporting

confidence: 91%

“…The low-dose allergen challenge model has been developed in order to administer a more physiologically relevant concentration of allergen repetitively over a period of days. Low-dose allergen challenge increases airway inflammation and bronchial hyper-reactivity [15][16][17] and is inhibited by ICS and antileukotriene drugs in ICS-naïve asthma patients [15,18]. The low-dose allergen challenge model has not been evaluated in patients taking ICS.…”

Section: Introductionmentioning

confidence: 99%

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High‐ and low‐dose allergen challenges in asthmatic patients using inhaled corticosteroids

Lee

Southworth

Booth

et al. 2015

Brit J Clinical Pharma

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AIMSThe inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high-and low-dose allergen challenges in asthmatic patients using ICS. METHODSTwenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day −1 ) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers. RESULTSThe high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1, but had no effect on FEV1 at 24 h after challenge or sputum measurements. CONCLUSIONSThe high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

High‐ and low‐dose allergen challenges in asthmatic patients using inhaled corticosteroids

Lee

Southworth

Booth

et al. 2015

Brit J Clinical Pharma

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“…In newborns and infants during the first year of life, failing to shift a Th2 cytokine profile to a Th1 profile has been associated with blood eosinophilia and serum markers of atopy (24). Others have demonstrated that there is no relationship between the number of eosinophils and an attenuated late asthmatic response with repeated low-dose allergen exposure (26). Therefore, investigation into the Th1/Th2 balance in very young mice outside of the BAL fluid compartment may help clarify the association between early life eosinophilia and a reduced later life allergic inflammatory response.…”

Section: Discussionmentioning

confidence: 95%

Early exposure to a nonhygienic environment alters pulmonary immunity and allergic responses

George¹,

White²,

Kulhánková³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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The hygiene hypothesis suggests that early life exposure to a nonhygienic environment that contains endotoxin reduces the risk of developing allergic diseases. The mechanisms underlying the hygiene hypothesis are unclear and may involve subtle immune system interactions that occur during maturation. Experimental objectives of this study were to use a novel animal model to test the hygiene hypothesis and to characterize early life immune system responses to a nonhygienic environment. Mice were reared in corn dust, a grain-processing byproduct with a high-endotoxin content and microbial products or in a low-endotoxin environment. The influence of early or later life exposure to corn dust on a subsequent allergen stimulus (ovalbumin) was assessed by bronchoalveolar lavage (BAL) cell analysis, lung histology, serum IgE, and BAL cytokine measurements. The influence of the corn dust environment on the developing pulmonary immune system was assessed by BAL cell analysis and immunostaining of lung tissue. The corn dust environment contained significantly more endotoxin (P < 0.001), and the dust exposures attenuated the cellular inflammatory response to ovalbumin in the adult mouse (P < 0.01) but did not reduce serum IgE levels or alter baseline BAL fluid proinflammatory cytokine levels. The corn dust environment did not induce significant neutrophilia in lavage fluid but significantly increased the number of antigen-presenting cells in alveolar walls early in life by approximately 37%. In conclusion, exposure to a nonhygienic environment did not induce significant airway neutrophilia, yet altered the population of immunologically active cells in the lung and reduced subsequent allergic inflammation.

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“…In this challenge setting, patients with atopic asthma were subjected to inhalations of fixed doses of allergen, titrated to cause minimal bronchoconstriction and administered once daily on 4-10 consecutive weekdays [1][2][3][4][5][6]. The procedure generates a distinct increase in airway hyperresponsiveness (AHR) to direct bronchoconstrictors [1][2][3][4][5][6].…”

mentioning

confidence: 99%

Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge

Ihre

Gyllfors²,

Gustafsson³

et al. 2006

Eur Respir J

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Repeated low-dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. The current authors performed a controlled study to evaluate the time course of changes in exhaled nitric oxide fraction (Fe,NO) and urinary biomarkers of airway inflammation.Eight subjects with mild allergic asthma completed two 7-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and were investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and Fe,NO and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine.Despite no change in pulmonary function (forced expiratory volume in one second mean¡SEM fall 0.3¡0.7 versus 0.6¡1.0%, for diluent and allergen, respectively) and no asthma symptoms, repeated allergen exposure, in contrast to diluent, caused significant increases in histamine responsiveness (2.3 doubling doses), an early and gradual increase in Fe,NO (up to a doubling from baseline) and a small increase in the mast cell marker 9a11b-prostaglandin F 2 after adenosine challenge.In conclusion, serial measurements of exhaled nitric oxide fraction have the potential to provide a very sensitive strategy for early detection of emerging airway inflammation and subsequent changes in airway hyperresponsiveness to histamine.

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Reduced late asthmatic response by repeated low-dose allergen exposure

Cited by 19 publications

References 36 publications

High‐ and low‐dose allergen challenges in asthmatic patients using inhaled corticosteroids

High‐ and low‐dose allergen challenges in asthmatic patients using inhaled corticosteroids

Early exposure to a nonhygienic environment alters pulmonary immunity and allergic responses

Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge

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