Bronchial Reactivity to Histamine Is Correlated With Airway Remodeling in Adults With Moderate to Severe Asthma

Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan.
Journal of Asthma (Impact Factor: 1.8). 10/2010; 47(8):841-8. DOI: 10.3109/02770903.2010.504876
Source: PubMed


Chronic eosinophilic inflammation may promote airway remodeling, including thickening of the reticular basement membrane (RBM), hypertrophy and hyperplasia of the airway smooth muscles (ASM), and an increase in the production of tenascin. The authors examined the correlation between airway remodeling and bronchial reactivity to histamine (Hist) and acetylcholine (ACh) in patients with moderate to severe asthma.
In 30 adult patients with asthma, the authors assessed bronchial hyperresponsiveness (BHR) to various concentrations of ACh and Hist by measuring decreases in forced expiratory volume in one second (FEV₁) of >20% from the preprovocation state, and % recoveries of FEV₁ after inhalation of β-stimulant. After corticosteroid therapy, the authors evaluated the thickening of RBM and ASM and the production of tenascin in bronchial specimens.
The % decrease in FEV₁ was correlated with the % recovery in FEV₁ after provocation by ACh or Hist. Hypertrophy of ASM was correlated with the % decrease in FEV₁ after provocation by Hist, but not by ACh. Thickening of ASM, up-regulation of tenascin in RBM, and duration of asthma were inversely correlated with the % recovery of FEV₁ after provocation by Hist, but not by ACh.
In adult patients with moderate to severe asthma, a strong bronchial contraction provoked by Hist and a subsequent small recovery indicate airway remodeling.

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Available from: Naomi Tsurikisawa, Jan 17, 2014
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    • "Airway remodeling in asthma includes increased ASM mass, reflecting myocyte proliferation.56–58 Hypertrophy of ASM is correlated with a decrease in FEV1 after provocation by histamine.59 Interestingly, vitamin D has antiproliferative effects on ASM, decelerating cell cycling and decreasing hyperplasia.60 "
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    ABSTRACT: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.
    Journal of Asthma and Allergy 04/2014; 7(7):23-30. DOI:10.2147/JAA.S46944
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    • "Moreover, airway wall remodeling can lead to airway inflammation and AHR [20]. As a characteristic of pathological change in asthma; airway remodeling was also the pathological basis of chronic, persistent, severe, steroid-resistant asthma, and irreversible airway obstruction [21-24]. "
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    ABSTRACT: Over-proliferation of airway smooth muscle cell (ASMC) is one of the important contributors to airway remodeling in asthma. The aim of this study was to investigate the effect of Shenmai injection (SMI) on the proliferation of the rat ASMC in asthma. Rats were randomly divided into three groups: the control group, the asthma group, and the SMI treatment group. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry staining were used to detect the mRNA and protein expression of transient receptor potential vanilloid 1 (TRPV1) and proliferating cell nuclear antigen (PCNA) in rat ASMC respectively. Intracellular Ca2+ concentration ( [Ca2+]i ) in rat ASMC were measured with Fluo-3/AM by confocal microscopy. The proliferation was detected by MTT assay. Compared with the control group, the asthma group showed an increased expression of TRPV1 and [Ca2+]i in rat ASMC. The expression of PCNA and absorbance of MTT assay in asthma rat ASMC was also significantly increased. SMI could significantly decrease the expression of TRPV1 channel and [Ca2+]i in the asthmatic rat ASMC. Furthermore, the expression of PCNA and absorbance of MTT assay in asthmatic rat ASMC was significantly reduced after SMI treatment. SMI may prevent asthma-induced ASMC over-proliferation probably by inhibiting the expression of TRPV1 channel, which regulates the intracellular calcium concentration.
    BMC Complementary and Alternative Medicine 09/2013; 13(1):221. DOI:10.1186/1472-6882-13-221 · 2.02 Impact Factor
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    ABSTRACT: Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma.
    Allergologia et Immunopathologia 03/2012; 40(2):108-16. DOI:10.1016/j.aller.2011.11.002 · 1.74 Impact Factor
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