Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of ...Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.展开更多
Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interst...Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.展开更多
Background:The aim of this review is to summarize the current evidence regarding small airway disease in asthma,focusing on recent advances in small airway pathophysiology,assessment and therapeutic implications.Metho...Background:The aim of this review is to summarize the current evidence regarding small airway disease in asthma,focusing on recent advances in small airway pathophysiology,assessment and therapeutic implications.Methods:A search in Medline was performed,using the keywords“small airways”,“asthma”,“oscillometry”,“nitrogen washout”and“imaging”.Our review was based on studies from adult asthmatic patients,although evidence from pediatric populations is also discussed.Results:In asthma,inflammation in small airways,increased mucus production and airway wall remodelling are the main pathogenetic mechanisms of small airway disease.Small airway dysfunction is a key component of asthma pathophysiology,leading to increased small airway resistance and airway closure,with subsequent ventilation inhomogeneities,hyperresponsiveness and airflow limitation.Classic tests of lung function,such as spirometry and body plethysmography are insensitive to detect small airway disease,providing only indirect measurements.As discussed in our review,both functional and imaging techniques that are more specific for small airways,such as oscillometry and the multiple breath nitrogen washout have delineated the role of small airways in asthma.Small airways disease is prevalent across all asthma disease stages and especially in severe disease,correlating with important clinical outcomes,such as asthma control and exacerbation frequency.Moreover,markers of small airways dysfunction have been used to guide asthma treatment and monitor response to therapy.Conclusions:Assessment of small airway disease provides unique information for asthma diagnosis and monitor-ing,with potential therapeutic implications.展开更多
Asthma is a heterogeneous disease that involves a complex interplay of genetic and environmental factors, leading to＇chronicinflammation and airway remodeling. The major features that lead to clinical symptoms are in...Asthma is a heterogeneous disease that involves a complex interplay of genetic and environmental factors, leading to＇chronicinflammation and airway remodeling. The major features that lead to clinical symptoms are infiltration of inflammatory cells, epithelial shedding, mucous gland hyperplasia, increased airway smooth muscle mass and contraction,展开更多
Background The immunologic response to allergens mediated by T lymphocytes is an incipient key element in the pathogenesis of asthma, and Thl/Th2 balance is regarded as the core of asthma pathogenesis. Notch is a sing...Background The immunologic response to allergens mediated by T lymphocytes is an incipient key element in the pathogenesis of asthma, and Thl/Th2 balance is regarded as the core of asthma pathogenesis. Notch is a single-pass transmembrane receptor protein that regulates differentiation, proliferation and apoptosis in a broad range of cells. It is considered that the Notch signal pathway works in every stage of T cell development and differentiation. Whether the pathway of asthma pathogenesis is related to Notch1 remains unknown. This study is aimed to investigate whether the pathway of asthma pathogenesis is related to Notch1 by examining the effect of knockdown of the Notch1 gene by small interfering RNA on T cell differentiation. Methods An OVA-induced asthma mouse model was established. The expression of Notch1 in the tissue and T cells of the lung from asthmatic mice was detected by RT-PCR and Western blotting. The expression of Notch1 and cytokine interleukin （IL）-4 and interferon （IFN）-γ in activated lung T cells was detected by RT-PCR and enzyme-linked immunosorbent assay after blocking Notch1 by small interfering RNA. Results The mRNA and protein expression of Notch1 increased significantly both in the lung tissue and lung T cells of asthmatic mice （both P 〈0.05）. IL-4 decreased and IFN-y increased significantly in active lung T cells after Notch1 was blocked by Notchl-specific small interfering RNA （IL-4： （2.51±0.51） pg/ml vs 0.64±0.27） pg/ml protein; IFN-γ： （21.72±4.24） pg/ml vs （39.79±4.09） pg/ml protein, P 〈0.05）. Conclusion This study demonstrated that the Notch1 signal might play a role in the pathogenesis of asthma by its involvement in Thl/Th2 differentiation.展开更多
OBJECTIVE： To investigate the effect of Gubenfangxiao decoction （GBFXD） on respiratory-syncytial-virus （RSV） -induced asthma and the expression of asthma susceptibility gene, orosomucoid 1-1ike protein 3 （ORMDL3...OBJECTIVE： To investigate the effect of Gubenfangxiao decoction （GBFXD） on respiratory-syncytial-virus （RSV） -induced asthma and the expression of asthma susceptibility gene, orosomucoid 1-1ike protein 3 （ORMDL3） in mice. METHODS： Seventy-two female BALB/c mice were randomly assigned to normal, model, GBFXD high dose, GBFXD moderate dose, GBFXD low dose and montelukast groups. An asthma model was induced via intraperitoneal injection and aerosol inhalation of ovalbumin （OVA） and repeated intranasal instillation of RSV in all mice, except those in the normal group. All treatments were administered at the first onset of asthma （within 8 weeks of model establishment） and the mice were euthanized after 28 days of treatment. The levels of transforming growth factor-β （TGF-β） and interleukin-6 （IL-6） in bronchoalveolar lavage fluid （BALF） of the mice were measured and the expression of asthma sus- ceptibility gene ORMDL3 in lung tissue was deter- mined using real-time polymerase chain reaction （RT-PCR） and western blotting. RESULTS： Expression of ORMDL3 and levels of TGF-β and IL-6 were significantly higher in the mod- el group （P 〈 0.05, P 〈 0.01） compared with the normal mice. Levels of ORMDL3, TGF-β and IL-6 were significantly lower in all three GBFXD treated groups （P 〈 0.05） compared with the model group. However, the levels in the GBFXD treatment groups did not differ significantly from the montelukast group. CONCLUSION： GBFXD had a therapeutic effect in this experimental model. The functional mechanism of GBFXD may involve multiple factors, including alleviation of airway inflammation, down-regulation of asthma susceptibility gene ORMDL3 and inhibition of airway remodeling.展开更多
基金supported by the National Natural Science Foundation of China(No.81970024).
文摘Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.
文摘Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.
基金DT is a recipient of a Long-Term Research Fellowship from the Eu-ropean Respiratory Society.
文摘Background:The aim of this review is to summarize the current evidence regarding small airway disease in asthma,focusing on recent advances in small airway pathophysiology,assessment and therapeutic implications.Methods:A search in Medline was performed,using the keywords“small airways”,“asthma”,“oscillometry”,“nitrogen washout”and“imaging”.Our review was based on studies from adult asthmatic patients,although evidence from pediatric populations is also discussed.Results:In asthma,inflammation in small airways,increased mucus production and airway wall remodelling are the main pathogenetic mechanisms of small airway disease.Small airway dysfunction is a key component of asthma pathophysiology,leading to increased small airway resistance and airway closure,with subsequent ventilation inhomogeneities,hyperresponsiveness and airflow limitation.Classic tests of lung function,such as spirometry and body plethysmography are insensitive to detect small airway disease,providing only indirect measurements.As discussed in our review,both functional and imaging techniques that are more specific for small airways,such as oscillometry and the multiple breath nitrogen washout have delineated the role of small airways in asthma.Small airways disease is prevalent across all asthma disease stages and especially in severe disease,correlating with important clinical outcomes,such as asthma control and exacerbation frequency.Moreover,markers of small airways dysfunction have been used to guide asthma treatment and monitor response to therapy.Conclusions:Assessment of small airway disease provides unique information for asthma diagnosis and monitor-ing,with potential therapeutic implications.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81170039）.
文摘Asthma is a heterogeneous disease that involves a complex interplay of genetic and environmental factors, leading to＇chronicinflammation and airway remodeling. The major features that lead to clinical symptoms are infiltration of inflammatory cells, epithelial shedding, mucous gland hyperplasia, increased airway smooth muscle mass and contraction,
基金This study was supported by the grants from the Major Program of Shanghai Education Committee Foundation （No. 09ZZ114） and the National Natural Science Foundation of China （No. 30971302）.
文摘Background The immunologic response to allergens mediated by T lymphocytes is an incipient key element in the pathogenesis of asthma, and Thl/Th2 balance is regarded as the core of asthma pathogenesis. Notch is a single-pass transmembrane receptor protein that regulates differentiation, proliferation and apoptosis in a broad range of cells. It is considered that the Notch signal pathway works in every stage of T cell development and differentiation. Whether the pathway of asthma pathogenesis is related to Notch1 remains unknown. This study is aimed to investigate whether the pathway of asthma pathogenesis is related to Notch1 by examining the effect of knockdown of the Notch1 gene by small interfering RNA on T cell differentiation. Methods An OVA-induced asthma mouse model was established. The expression of Notch1 in the tissue and T cells of the lung from asthmatic mice was detected by RT-PCR and Western blotting. The expression of Notch1 and cytokine interleukin （IL）-4 and interferon （IFN）-γ in activated lung T cells was detected by RT-PCR and enzyme-linked immunosorbent assay after blocking Notch1 by small interfering RNA. Results The mRNA and protein expression of Notch1 increased significantly both in the lung tissue and lung T cells of asthmatic mice （both P 〈0.05）. IL-4 decreased and IFN-y increased significantly in active lung T cells after Notch1 was blocked by Notchl-specific small interfering RNA （IL-4： （2.51±0.51） pg/ml vs 0.64±0.27） pg/ml protein; IFN-γ： （21.72±4.24） pg/ml vs （39.79±4.09） pg/ml protein, P 〈0.05）. Conclusion This study demonstrated that the Notch1 signal might play a role in the pathogenesis of asthma by its involvement in Thl/Th2 differentiation.
基金Supported by Natural Science Foundation of China(Effect of Gubenfangxiao Decoction on the Expression of Asthma Susceptibility Gene ORMDL3 and ADAM33 and its Signaling pathway,No.81173209)
文摘OBJECTIVE： To investigate the effect of Gubenfangxiao decoction （GBFXD） on respiratory-syncytial-virus （RSV） -induced asthma and the expression of asthma susceptibility gene, orosomucoid 1-1ike protein 3 （ORMDL3） in mice. METHODS： Seventy-two female BALB/c mice were randomly assigned to normal, model, GBFXD high dose, GBFXD moderate dose, GBFXD low dose and montelukast groups. An asthma model was induced via intraperitoneal injection and aerosol inhalation of ovalbumin （OVA） and repeated intranasal instillation of RSV in all mice, except those in the normal group. All treatments were administered at the first onset of asthma （within 8 weeks of model establishment） and the mice were euthanized after 28 days of treatment. The levels of transforming growth factor-β （TGF-β） and interleukin-6 （IL-6） in bronchoalveolar lavage fluid （BALF） of the mice were measured and the expression of asthma sus- ceptibility gene ORMDL3 in lung tissue was deter- mined using real-time polymerase chain reaction （RT-PCR） and western blotting. RESULTS： Expression of ORMDL3 and levels of TGF-β and IL-6 were significantly higher in the mod- el group （P 〈 0.05, P 〈 0.01） compared with the normal mice. Levels of ORMDL3, TGF-β and IL-6 were significantly lower in all three GBFXD treated groups （P 〈 0.05） compared with the model group. However, the levels in the GBFXD treatment groups did not differ significantly from the montelukast group. CONCLUSION： GBFXD had a therapeutic effect in this experimental model. The functional mechanism of GBFXD may involve multiple factors, including alleviation of airway inflammation, down-regulation of asthma susceptibility gene ORMDL3 and inhibition of airway remodeling.
