Mouse allergen exposure, wheeze and atopy in the first seven years of life

PubMed Central

Phipatanakul, W.; Celedón, J. C.; Hoffman, E. B.; Abdulkerim, H.; Ryan, L. M.; Gold, D. R.

2008-01-01

Background Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood. Objective To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life. Methods Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months. Results Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis. Conclusions Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life. PMID:18616677

IL-23 secreted by bronchial epithelial cells contributes to allergic sensitization in asthma model: role of IL-23 secreted by bronchial epithelial cells.

PubMed

Lee, Hyun Seung; Park, Da-Eun; Lee, Ji-Won; Chang, Yuna; Kim, Hye Young; Song, Woo-Jung; Kang, Hye-Ryun; Park, Heung-Woo; Chang, Yoon-Seok; Cho, Sang-Heon

2017-01-01

IL-23 has been postulated to be a critical mediator contributing to various inflammatory diseases. Dermatophagoides pteronyssinus (Der p) is one of the most common inhalant allergens. However, the role of IL-23 in Der p-induced mouse asthma model is not well understood, particularly with regard to the development of allergic sensitization in the airways. The objective of this study was to evaluate roles of IL-23 in Der p sensitization and asthma development. BALB/c mice were repeatedly administered Der p intranasally to develop Der p allergic sensitization and asthma. After Der p local administration, changes in IL-23 expression were examined in lung tissues and primary epithelial cells. Anti-IL-23p19 antibody was given during the Der p sensitization period, and its effects were examined. Effects of anti-IL-23p19 antibody at bronchial epithelial levels were also examined in vitro. The expression of IL-23 at bronchial epithelial layers was increased after Der p local administration in mouse. In Der p-induced mouse models, anti-IL-23p19 antibody treatment during allergen sensitization significantly diminished Der p allergic sensitization and several features of allergic asthma including the production of Th2 cytokines and the population of type 2 innate lymphoid cells in lungs. The activation of dendritic cells in lung-draining lymph nodes was also reduced by anti-IL-23 treatment. In murine lung alveolar type II-like epithelial cell line (MLE-12) cells, IL-23 blockade prevented cytokine responses to Der p stimulation, such as IL-1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-33, and also bone marrow-derived dendritic cell activation. In conclusion, IL-23 is another important bronchial epithelial cell-driven cytokine which may contribute to the development of house dust mite allergic sensitization and asthma. Copyright © 2017 the American Physiological Society.

Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.

PubMed

Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Inci, Cigdem; Filinte, Deniz; Kombak, Faruk Erdem; Karaoz, Erdal; Akkoc, Tunc

2014-05-01

New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (P<0.001). Intravenous administration of mCB-MSC significantly reduced these histopathological changes in both distal and proximal airways (P<0.001). We showed that GFP-labeled MSCs were located in the lungs of OVA group 2weeks after intravenous induction. mCB-MSCs also significantly promoted Treg response in ovalbumin-treated mice (OVA+MSC group) (P<0.037). Our studies revealed that mCB-MSCs migrated to lung tissue and suppressed histopathological changes in murine model of asthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. Copyright © 2014 Elsevier B.V. All rights reserved.

Allergens in Urban Schools and Homes of Children with Asthma

PubMed Central

Permaul, Perdita; Hoffman, Elaine B.; Fu, Chunxia; Sheehan, William J.; Baxi, Sachin N.; Gaffin, Jonathan M.; Lane, Jeffrey P.; Bailey, Ann; King, Eva; Chapman, Martin D.; Gold, Diane R.; Phipatanakul, Wanda

2012-01-01

Background Most studies of indoor allergens have focused on the home environment. However, schools may be an important site of allergen exposure for children with asthma. We compared school allergen exposure to home exposure in a cohort of children with asthma. Correlations between settled dust and airborne allergen levels in classrooms were examined. Methods Settled dust and airborne samples from 12 inner-city schools were analyzed for indoor allergens using multiplex array technology (MARIA). School samples were linked to students with asthma enrolled in the School Inner-City Asthma Study (SICAS). Settled dust samples from students’ bedrooms were analyzed similarly. Results From schools, 229 settled dust and 197 airborne samples were obtained. From homes, 118 settled dust samples were obtained. Linear mixed regression models of log-transformed variables showed significantly higher settled dust levels of mouse, cat and dog allergens in schools than homes (545% higher for Mus m 1, estimated absolute difference 0.55 μg/g, p<0.0001; 198% higher for Fel d 1, estimated absolute difference 0.13 μg/g, p=0.0033; and 144% higher for Can f 1, estimated absolute difference 0.05 μg/g, p=0.0008). Airborne and settled dust Mus m 1 levels in classrooms were moderately correlated (r=0.48; p< 0.0001). There were undetectable to very low levels of cockroach and dust mite allergens in both homes and schools. Conclusions Mouse allergen levels in schools were substantial. In general, cat and dog allergen levels were low, but detectable, and were higher in schools. Aerosolization of mouse allergen in classrooms may be a significant exposure for students. Further studies are needed to evaluate the effect of indoor allergen exposure in schools on asthma morbidity in students with asthma. PMID:22672325

S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.

PubMed

Yoon, Sun-Young; Hong, Gyong Hwa; Kwon, Hyouk-Soo; Park, Sunjoo; Park, So Young; Shin, Bomi; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-06-03

Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model

PubMed Central

2010-01-01

Background The dust mite Blomia tropicalis is an important source of aeroallergens in tropical areas. Although a mouse model for B. tropicalis extract (BtE)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol. Objectives This work had two objectives. The first was to study the anti-B. tropicalis allergic responses in different mouse strains using a short-term model of respiratory allergy to BtE. This study included the comparison of the allergic responses elicited by BtE with those elicited by ovalbumin in mice of the strain that responded better to BtE sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low BtE doses. Methods Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 μg of BtE on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 μg of BtE. A/J mice, that were the best responders to BtE sensitization, were used to compare the B. tropicalis-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of BtE. Results Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-BtE IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with BtE induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low BtE dose (10 μg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses. Conclusions The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE. PMID:20433763

Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma.

PubMed

Patel, Kruti R; Bai, Yan; Trieu, Kenneth G; Barrios, Juliana; Ai, Xingbin

2017-10-01

Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation. We found that allergen exposure in neonatal mice, but not in adult mice, elevated the level and activity of cholinergic nerves (termed neuroplasticity). We demonstrated that cholinergic neuroplasticity is necessary for the induction of persistent AHR after neonatal exposure during rescue assays in mice deficient in neuroplasticity. In addition, early intervention with cholinergic receptor muscarinic (ChRM)-3 blocker reversed the progression of AHR in the neonatal exposure model, whereas β2-adrenoceptor agonists had no such effect. Together, our findings demonstrate a functional relationship between cholinergic neuroplasticity and ASM contractile phenotypes that operates uniquely in early life to induce persistent AHR after allergen exposure. Targeting ChRM3 may have disease-modifying benefits in childhood asthma.-Patel, K. R., Bai, Y., Trieu, K. G., Barrios, J., Ai, X. Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma. © FASEB.

Curcumin reduces lung inflammation via Wnt/β-catenin signaling in mouse model of asthma.

PubMed

Yang, Xia; Lv, Jian-Ning; Li, Hui; Jiao, Bo; Zhang, Qiu-Hong; Zhang, Yong; Zhang, Jie; Liu, Yan-Qin; Zhang, Ming; Shan, Hu; Zhang, Jin-Zhao; Wu, Run-Miao; Li, Ya-Li

2017-05-01

Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/β-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/β-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma. C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days. Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. DCs were isolated from mouse bone morrow. The surface markers CD40, CD86 and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and the function of DCs was detected by mixed lymphocyte reaction. The expression of GSK-3β and β-catenin was detected by Western Blot. Results showed that OVA increased the number of inflammatory factors in BALF (bronchoalveolar lavage fluid), elevated lung inflammation scores in mice. Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice. Curcumin activated Wnt/β-catenin signaling pathway in DCs and asthmatic mouse lungs. Curcumin could influence the morphology and function of DCs, ease asthma symptom and inflammatory reaction through the activation of Wnt/β-catenin signaling. These results provide new evidence new evidence for application of curcumin on asthma.

Inhibition of TRPC3 downregulates airway hyperresponsiveness, remodeling of OVA-sensitized mouse.

PubMed

Wang, Lingwei; Li, Jie; Zhang, Jian; He, Qi; Weng, Xuanwen; Huang, Yanmei; Guan, Minjie; Qiu, Chen

2017-02-26

Airway hyperresponsiveness (AHR), airway remodeling and inflammation are the fundamental pathological alterations that occur in asthma. Transient receptor potential canonical 3 (TRPC3) has been implicated in diverse functions of airway smooth muscle cells (ASMCs) in asthma. However, the underlying mechanisms remain incompletely understood. We investigated the mRNA and protein expression of TRPC3 in ASMCs from normal and OVA-sensitized mouse. And the effects of inhibition or knockdown of TRPC3 with Ethyl-1- (4- (2,3,3-trichloroacrylamide) phenyl) -5 - (trifluoromethyl) -1H -pyrazole -4-carboxylate (Pyr3) and lentiviral shRNA on OVA-sensitized mouse AHR, airway remodeling, circulating inflammatory cytokines, cell proliferation and migration. We found that TRPC3 mRNA and protein expression levels were significantly increased in ASMCs from OVA-sensitized mouse. Inhibiting TRPC3 with continuous subcutaneous administration of Pyr3 decreased enhanced pause (Penh) of OVA-sensitized mouse. Meanwhile, both Pyr3 and lentiviral shRNA treatment of ASMCs in OVA-sensitized mouse significantly decreased their proliferation and migration. These results suggest that TRPC3 plays a critical role in asthma and represents a promising new target for asthma treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

l-Arginine administration attenuates airway inflammation by altering l-arginine metabolism in an NC/Nga mouse model of asthma.

PubMed

Zhang, Ran; Kubo, Masayuki; Murakami, Ikuo; Setiawan, Heri; Takemoto, Kei; Inoue, Kiyomi; Fujikura, Yoshihisa; Ogino, Keiki

2015-05-01

Changes in l-arginine metabolism, including increased arginase levels and decreased nitric oxide production, are involved in the pathophysiology of asthma. In this study, using an intranasal mite-induced NC/Nga mouse model of asthma, we examined whether administration of l-arginine ameliorated airway hyperresponsiveness and inflammation by altering l-arginine metabolism. Experimental asthma was induced in NC/Nga mice via intranasal administration of mite crude extract (50 µg/day) on 5 consecutive days (days 0-4, sensitization) and on day 11 (challenge). Oral administration of l-arginine (250 mg/kg) was performed twice daily on days 5-10 for prevention or on days 11-13 for therapy. On day 14, we evaluated the inflammatory airway response (airway hyperresponsiveness, the number of cells in the bronchoalveolar lavage fluid, and the changes in pathological inflammation of the lung), arginase expression and activity, l-arginine bioavailability, and the concentration of NOx, the end products of nitric oxide. Treatment with l-arginine ameliorated the mite-induced inflammatory airway response. Furthermore, l-arginine administration attenuated the increases in arginase expression and activity and elevated the NOx levels by enhancing l-arginine bioavailability. These findings indicate that l-arginine administration may contribute to the improvement of asthmatic symptoms by altering l-arginine metabolism.

Mega-dose vitamin C attenuated lung inflammation in mouse asthma model.

PubMed

Jeong, Young-Joo; Kim, Jin-Hee; Kang, Jae Seung; Lee, Wang Jae; Hwang, Young-Il

2010-12-01

Asthma is a Th2-dependent disease mediated by IgE and Th2 cytokines, and asthmatic patients suffer from oxidative stresses from abnormal airway inflammation. Vitamin C is a micro-nutrient functioning as an antioxidant. When administered at a mega-dose, vitamin C has been reported to shift immune responses toward Th1. Thus, we tried to determine whether vitamin C exerted beneficial effects in asthma animal model. Asthma was induced in mice by sensitizing and challenging with ovalbumin. At the time of challenge, 3~5 mg of vitamin C was administered and the effects were evaluated. Vitamin C did not modulate Th1/Th2 balance in asthma model. However, it decreased airway hyperreactivity to methacholine, decreased inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration. These results suggest that vitamin C administered at the time of antigen challenge exerted anti-inflammatory effects. Further studies based on chronic asthma model are needed to evaluate a long-term effect of vitamin C in asthma. In conclusion, even though vitamin C did not show any Th1/Th2 shifting effects in this experiment, it still exerted moderate anti-inflammatory effects. Considering other beneficial effects and inexpensiveness of vitamin C, mega-dose usage of vitamin C could be a potential supplementary modality for the management of asthma.

TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma.

PubMed

Nadeem, Ahmed; Siddiqui, Nahid; Al-Harbi, Naif O; Al-Harbi, Mohammed M; Ahmad, Sheikh F

2016-04-01

Toll-like receptors (TLRs) through innate immune system recognize pathogen associated molecular patterns and play an important role in host defense against bacteria, fungi and viruses. TLR-7 is responsible for sensing single stranded nucleic acids of viruses but its activation has been shown to be protective in mouse models of asthma. The NADPH oxidase (NOX) enzymes family mainly produces reactive oxygen species (ROS) in the lung and is involved in regulation of airway inflammation in response to TLRs activation. However, NOX-4 mediated signaling in response to TLR-7 activation in a mouse model of allergic asthma has not been explored previously. Therefore, this study investigated the role TLR-7 activation and downstream oxidant-antioxidant signaling in a murine model of asthma. Mice were sensitized with ovalbumin (OVA) intraperitoneally and treated with TLR-7 agonist, resiquimod (RSQ) intranasally before each OVA challenge from days 14 to 16. Mice were then assessed for airway reactivity, inflammation, and NOX-4 and nuclear factor E2-related factor 2 (Nrf2) related signaling [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides and copper/zinc superoxide dismutase (Cu/Zn SOD)]. Treatment with RSQ reduced allergen induced airway reactivity and inflammation. This was paralleled by a decrease in ROS which was due to induction of Nrf2 and Cu/Zn SOD in RSQ treated group. Inhibition of MyD88 reversed RSQ-mediated protective effects on airway reactivity/inflammation due to reduction in Nrf2 signaling. SOD inhibition produced effects similar to MyD88 inhibition. The current study suggests that TLR-7 agonist is beneficial and may be developed into a therapeutic option in allergic asthma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression

PubMed Central

Campbell, John D.; Buckland, Karen F.; McMillan, Sarah J.; Kearley, Jennifer; Oldfield, William L.G.; Stern, Lawrence J.; Grönlund, Hans; van Hage, Marianne; Reynolds, Catherine J.; Boyton, Rosemary J.; Cobbold, Stephen P.; Kay, A. Barry; Altmann, Daniel M.; Larché, Mark

2009-01-01

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other (“linked”) epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10+ T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti–IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans. PMID:19528258

Variation in Airway Responsiveness of Male C57BL/6 Mice from 5 Vendors

PubMed Central

Chang, Herng-Yu Sucie; Mitzner, Wayne; Watson, Julie

2012-01-01

Mice are now the most commonly used animal model for the study of asthma. The mouse asthma model has many characteristics of the human pathology, including allergic sensitization and airway hyperresponsiveness. Inbred strains are commonly used to avoid variations due to genetic background, but variations due to rearing environment are not as well recognized. After a change in mouse vendors and a switch from C57BL/6J mice to C57BL/6N mice, we noted significant differences in airway responsiveness between the substrains. To further investigate the effect of vendor, we tested C57BL/6N mice from 3 other vendors and found significant differences between several of the substrains. To test whether this difference was due to genetic drift or rearing environment, we purchased new groups of mice from all 5 vendors, bred them in separate vendor-specific groups under uniform environmental conditions, and tested male first generation (F1) offspring at 8 to 10 wk of age. These F1 mice showed no significant differences in airway responsiveness, indicating that the rearing environment rather than genetic differences was responsible for the initial variation in pulmonary phenotype. The environmental factors that caused the phenotypic variation are unknown. However, differences between vendor in feed components, bedding type, or microbiome could have contributed. Whatever the basis, investigators using mouse models of asthma should be cautious in comparing data from mice obtained from different vendors. PMID:23043804

Fatty Acid Binding Protein 4 Regulates VEGF-Induced Airway Angiogenesis and Inflammation in a Transgenic Mouse Model

PubMed Central

Ghelfi, Elisa; Yu, Chen-Wei; Elmasri, Harun; Terwelp, Matthew; Lee, Chun G.; Bhandari, Vineet; Comhair, Suzy A.; Erzurum, Serpil C.; Hotamisligil, Gökhan S.; Elias, Jack A.; Cataltepe, Sule

2014-01-01

Neovascularization of the airways occurs in several inflammatory lung diseases, including asthma. Vascular endothelial growth factor (VEGF) plays an important role in vascular remodeling in the asthmatic airways. Fatty acid binding protein 4 (FABP4 or aP2) is an intracellular lipid chaperone that is induced by VEGF in endothelial cells. FABP4 exhibits a proangiogenic function in vitro, but whether it plays a role in modulation of angiogenesis in vivo is not known. We hypothesized that FABP4 promotes VEGF-induced airway angiogenesis and investigated this hypothesis with the use of a transgenic mouse model with inducible overexpression of VEGF165 under a CC10 promoter [VEGF-TG (transgenic) mice]. We found a significant increase in FABP4 mRNA levels and density of FABP4-expressing vascular endothelial cells in mouse airways with VEGF overexpression. FABP4−/− mouse airways showed a significant decrease in neovessel formation and endothelial cell proliferation in response to VEGF overexpression. These alterations in airway vasculature were accompanied by attenuated expression of proinflammatory mediators. Furthermore, VEGF-TG/FABP4−/− mice showed markedly decreased expression of endothelial nitric oxide synthase, a well-known mediator of VEGF-induced responses, compared with VEGF-TG mice. Finally, the density of FABP4-immunoreactive vessels in endobronchial biopsy specimens was significantly higher in patients with asthma than in control subjects. Taken together, these data unravel FABP4 as a potential target of pathologic airway remodeling in asthma. PMID:23391391

Cord blood versus age 5 mononuclear cell proliferation on IgE and asthma

PubMed Central

2010-01-01

Background Fetal immune responses following exposure of mothers to allergens during pregnancy may influence the subsequent risk of childhood asthma. However, the association of allergen-induced cord blood mononuclear cell (CBMC) proliferation and cytokine production with later allergic immune responses and asthma has been controversial. Our objective was to compare indoor allergen-induced CBMC with age 5 peripheral blood mononuclear cell (PBMC) proliferation and determine which may be associated with age 5 allergic immune responses and asthma in an inner city cohort. Methods As part of an ongoing cohort study of the Columbia Center for Children's Environmental Health (CCCEH), CBMCs and age 5 PBMCs were cultured with cockroach, mouse, and dust mite protein extracts. CBMC proliferation and cytokine (IL-5 and IFN-γ) responses, and age 5 PBMC proliferation responses, were compared to anti-cockroach, anti-mouse, and anti-dust mite IgE levels, wheeze, cough, eczema and asthma. Results Correlations between CBMC and age 5 PBMC proliferation in response to cockroach, mouse, and dust mite antigens were nonsignificant. Cockroach-, mouse-, and dust mite-induced CBMC proliferation and cytokine responses were not associated with allergen-specific IgE at ages 2, 3, and 5, or with asthma and eczema at age 5. However, after adjusting for potential confounders, age 5 cockroach-induced PBMC proliferation was associated with anti-cockroach IgE, total IgE, and asthma (p < 0.05). Conclusion In contrast to allergen-induced CBMC proliferation, age 5 cockroach-induced PBMC proliferation was associated with age 5 specific and total IgE, and asthma, in an inner-city cohort where cockroach allergens are prevalent and exposure can be high. PMID:20684781

Ovalbumin-induced allergic inflammation lead to structural alterations in mouse model and protective effects of intranasal curcumin: A comparative study.

PubMed

Subhashini; Chauhan, P S; Singh, R

2016-01-01

Antigen exposure and persistent inflammation leads to structural changes in the asthmatic airways which are collectively termed as "airway remodelling". Presently available asthma medications ameliorate inflammations but are unable to prevent or reverse the airway remodelling process as most of the treatment strategies are only focused on inflammation instead of remodelling. Curcumin, a phytochemical present in the rhizome of Curcuma longa is well known for its anti-inflammatory activity; however, the main drawback is its poor bioavailability which limits its therapeutic approval. So, the effect of nasal curcumin on acute and chronic asthma has been studied where short exposure to ovalbumin (4 days) represents acute phase whereas repeated exposures for longer (twice per week till 5 weeks) represents chronic asthma. Disodium cromoglycate (DSCG, 50mg/kg, i.p.) and dexamethasone (1mg/kg, i.p.) were used as standard drugs in acute and chronic model of asthma respectively. OVA-induced airway inflammation initiated in acute stage led to remodelling due to persistent inflammation, epithelial and sub epithelial thickening (smooth muscle thickening), extracellular matrix (ECM) deposition, goblet cell hyperplasia and mucus plug formation. Intranasal curcumin is effective in inhibiting airway inflammation and remodelling both by maintaining the structural integrity of lungs in terms of inflammation, airway wall thickening and mucus production. Our findings suggest that curcumin administered through nasal route might prove therapeutically efficient in inhibiting allergic airway inflammations and maintaining structural integrity in the mouse model of allergic asthma. This may lead to the development of curcumin aerosol in near future. Copyright © 2016 SEICAP. Published by Elsevier Espana. All rights reserved.

ASSESSMENT OF ALLERGIC IMMUNE RESPONSES TO INDOOR AIR FUNGAL CONTAMINANTS

EPA Science Inventory

We are using a mouse model to assess immune and inflammatory responses as well as changes in respiratory function and pathology characteristic of allergic asthma to fungal extracts M. anisopliae (MACA), S. chartarum (SCE), and P. chrysogenum (PCE). This model will be useful to a...

Comparative study of Korean White Ginseng and Korean Red Ginseng on efficacies of OVA-induced asthma model in mice.

PubMed

Lim, Chi-Yeon; Moon, Jeong-Min; Kim, Bu-Yeo; Lim, Se-Hyun; Lee, Guem-San; Yu, Hak-Sun; Cho, Su-In

2015-01-01

Korean ginseng is a well-known medicinal herb that has been widely used in traditional medicine to treat various diseases, including asthma. Ginseng can be classified as white ginseng (WG) or red ginseng (RG), according to processing conditions. In this study, the authors compared the efficacies of these two ginseng types in a mouse model of acute asthma. To produce the acute asthma model, BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide, and then challenged with OVA. WG and RG extracts were administered to mice orally. The influences of WG and RG on airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a in serum were investigated. Cytokine production by lymphocytes isolated from peribronchial lymph nodes and histopathological changes was also examined. In OVA-sensitized mice, both WG and RG reduced AHR and suppressed immune cell infiltration in bronchoalveolar regions. BALF OVA-specific IgE levels were significantly lower in RG-treated OVA-sensitized mice than in the OVA-sensitized control group. WG and RG also suppressed inflammatory cytokine production by peribronchial lymphocytes. Histopathological findings showed reduced inflammatory cell infiltration and airway remodeling (e.g., epithelial hyperplasia) in WG- and RG-treated OVA mice compared with OVA controls. In this study, WG and RG showed antiasthmatic effects in an OVA-sensitized mouse model, and the efficacies of RG were found to be better than those of WG.

Down-regulation of Glutathione S-transferase Pi in Asthma Contributes to Enhanced Oxidative Stress

PubMed Central

Schroer, Kathy T.; Gibson, Aaron M.; Sivaprasad, Umasundari; Bass, Stacey A.; Ericksen, Mark B.; Wills-Karp, Marsha; LeCras, Tim; Fitzpatrick, Anne M.; Brown, Lou Ann S.; Stringer, Keith F.; Khurana Hershey, Gurjit K.

2011-01-01

Background Glutathione S-transferase Pi (GSTPi) is the predominant redox regulator in the lung. While evidence implicates an important role for GSTPi in asthma, the mechanism for this has remained elusive. Objectives To determine how GSTPi is regulated in asthma and to elucidate its role in maintaining redox homeostasis. Methods We elucidated the regulation of GSTPi in children with asthma and utilized murine models of asthma to determine the role of GSTPi in redox homeostasis. Measurements and Main Results Our findings demonstrate that GSTPi transcript levels are markedly down-regulated in allergen and IL-13 treated mouse models of asthma via STAT6 dependent and independent pathways. Nuclear factor-erythroid 2 related factor 2 (Nrf2) was also down-regulated in these models. The decrease in GSTPi expression was associated with decreased total GST activity in the lungs of mice. Examination of cystine intermediates uncovered a functional role for GSTPi in regulating Cys oxidation, whereby GSTPi-deficient mice exhibited increased oxidative stress (increase in % cystine) compared with wild-type mice following allergen challenge. GSTPi expression was similarly down-regulated in children with asthma. Conclusions These data collectively suggest that down-regulation of GSTPi following allergen challenge may contribute to the asthma phenotype due to disruption of redox homeostasis and increased oxidative stress. Furthermore, GSTPi may be an important therapeutic target for asthma, and evaluation of GSTPi expression may prove beneficial in identifying individuals who would benefit from therapy targeting this pathway. PMID:21570714

Role of breast milk in a mouse model of maternal transmission of asthma susceptibility.

PubMed

Leme, Adriana S; Hubeau, Cedric; Xiang, Yuhong; Goldman, Alejandra; Hamada, Kaoru; Suzaki, Yasue; Kobzik, Lester

2006-01-15

Epidemiologic data suggest a link between nursing by asthmatic mothers and increased risk of allergy in babies. We sought to experimentally test the potential contribution of breast milk mediator(s) in a mouse model of maternal transmission of asthma risk by evaluating the effect of adoptive nursing on asthma susceptibility in the offspring. We measured airway hyperresponsiveness (AHR) and allergic airway inflammation (AI) after an intentionally suboptimal OVA Ag sensitization, tested the allergen independence of the maternal effect by using a second allergen, casein, for sensitization of the baby mice, and tested the potential role of cytokines by measuring their levels in breast milk. Offspring of asthmatic, but not normal, mothers showed AHR and AI, indicating a maternal transfer of asthma risk. After adoptive nursing, both groups (litters born to asthmatic mothers and nursed by normal mothers, and normal babies nursed by asthmatic mothers) showed AHR (enhanced pause after methacholine aerosol, 50 mg/ml, 3.7 +/- 0.7, 4.2 +/- 0.5, respectively, vs 1.1 +/- 0.1 normal controls, n = 25, p < 0.01) and AI, seen as eosinophilia on histology and bronchoalveolar lavage (40.7 +/- 4.5%, 28.7 +/- 3.7%, vs 1.0 +/- 0.5% normals, n = 25, p < 0.01) after OVA sensitization. Similar results using casein allergen were observed. Multiplex assays for cytokines (IFN-gamma, IL-2, IL-4, IL-5, TNF-alpha, and IL-13) in breast milk were negative. Breast milk is sufficient, but not necessary, to mediate allergen-independent maternal transmission of asthma risk to offspring.

Prevention of Asthma Exacerbation in a Mouse Model by Simultaneous Inhibition of NF-κB and STAT6 Activation Using a Chimeric Decoy Strategy.

PubMed

Miyake, Tetsuo; Miyake, Takashi; Sakaguchi, Makoto; Nankai, Hirokazu; Nakazawa, Takahiro; Morishita, Ryuichi

2018-03-02

Transactivation of inflammatory and immune mediators in asthma is tightly regulated by nuclear factor κB (NF-κB) and signal transducer and activator of transcription 6 (STAT6). Therefore, we investigated the efficacy of simultaneous inhibition of NF-κB and STAT6 using a chimeric decoy strategy to prevent asthma exacerbation. The effects of decoy oligodeoxynucleotides were evaluated using an ovalbumin-induced mouse asthma model. Ovalbumin-sensitized mice received intratracheal administration of decoy oligodeoxynucleotides 3 days before ovalbumin challenge. Fluorescent-dye-labeled decoy oligodeoxynucleotides could be detected in lymphocytes and macrophages in the lung, and activation of NF-κB and STAT6 was inhibited by chimeric decoy oligodeoxynucleotide transfer. Consequently, treatment with chimeric or NF-κB decoy oligodeoxynucleotides protected against methacholine-induced airway hyperresponsiveness, whereas the effect of chimeric decoy oligodeoxynucleotides was significantly greater than that of NF-κB decoy oligodeoxynucleotides. Treatment with chimeric decoy oligodeoxynucleotides suppressed airway inflammation through inhibition of overexpression of interleukin-4 (IL-4), IL-5, and IL-13 and inflammatory infiltrates. Histamine levels in the lung were reduced via suppression of mast cell accumulation. A significant reduction in mucin secretion was observed due to suppression of MUC5AC gene expression. Interestingly, the inhibitory effects on IL-5, IL-13, and histamine secretion were achieved by transfer of chimeric decoy oligodeoxynucleotides only. This novel therapeutic approach could be useful to treat patients with various types of asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Propofol Attenuates Airway Inflammation in a Mast Cell-Dependent Mouse Model of Allergic Asthma by Inhibiting the Toll-like Receptor 4/Reactive Oxygen Species/Nuclear Factor κB Signaling Pathway.

PubMed

Li, Hong-Yi; Meng, Jing-Xia; Liu, Zhen; Liu, Xiao-Wen; Huang, Yu-Guang; Zhao, Jing

2018-06-01

Propofol, an intravenous anesthetic agent widely used in clinical practice, is the preferred anesthetic for asthmatic patients. This study was designed to determine the protective effect and underlying mechanisms of propofol on airway inflammation in a mast cell-dependent mouse model of allergic asthma. Mice were sensitized by ovalbumin (OVA) without alum and challenged with OVA three times. Propofol was given intraperitoneally 0.5 h prior to OVA challenge. The inflammatory cell count and production of cytokines in the bronchoalveolar lavage fluid (BALF) were detected. The changes of lung histology and key molecules of the toll-like receptor 4 (TLR4)/reactive oxygen species (ROS)/NF-κB signaling pathway were also measured. The results showed that propofol significantly decreased the number of eosinophils and the levels of IL-4, IL-5, IL-6, IL-13, and TNF-α in BALF. Furthermore, propofol significantly attenuated airway inflammation, as characterized by fewer infiltrating inflammatory cells and decreased mucus production and goblet cell hyperplasia. Meanwhile, the expression of TLR4, and its downstream signaling adaptor molecules--myeloid differentiation factor 88 (MyD88) and NF-κB, were inhibited by propofol. The hydrogen peroxide and methane dicarboxylic aldehyde levels were decreased by propofol, and the superoxide dismutase activity was increased in propofol treatment group. These findings indicate that propofol may attenuate airway inflammation by inhibiting the TLR4/MyD88/ROS/NF-κB signaling pathway in a mast cell-dependent mouse model of allergic asthma.

Effect of an Integrated Pest Management Intervention on Asthma Symptoms Among Mouse-Sensitized Children and Adolescents With Asthma: A Randomized Clinical Trial.

PubMed

Matsui, Elizabeth C; Perzanowski, Matthew; Peng, Roger D; Wise, Robert A; Balcer-Whaley, Susan; Newman, Michelle; Cunningham, Amparito; Divjan, Adnan; Bollinger, Mary E; Zhai, Shuyan; Chew, Ginger; Miller, Rachel L; Phipatanakul, Wanda

2017-03-14

Professionally delivered integrated pest management (IPM) interventions can reduce home mouse allergen concentrations, but whether they reduce asthma morbidity among mouse-sensitized and exposed children and adolescents is unknown. To determine the effect of an IPM intervention on asthma morbidity among mouse-sensitized and exposed children and adolescents with asthma. Randomized clinical trial conducted in Baltimore, Maryland, and Boston, Massachusetts. Participants were mouse-sensitized and exposed children and adolescents (aged 5-17 years) with asthma randomized to receive professionally delivered IPM plus pest management education or pest management education alone. Enrollment occurred between May 2010 and August 2014; the final follow-up visit occurred on September 25, 2015. Integrated pest management consisted of application of rodenticide, sealing of holes that could serve as entry points for mice, trap placement, targeted cleaning, allergen-proof mattress and pillow encasements, and portable air purifiers. Infestation was assessed every 3 months, and if infestation persisted or recurred, additional treatments were delivered. All participants received pest management education, which consisted of written material and demonstration of the materials needed to set traps and seal holes. The primary outcome was maximal symptom days defined as the highest number of days of symptoms in the previous 2 weeks among 3 types of symptoms (days of slowed activity due to asthma; number of nights of waking with asthma symptoms; and days of coughing, wheezing, or chest tightness) across 6, 9, and 12 months. Of 361 children and adolescents who were randomized (mean [SD] age, 9.8 [3.2] years; 38% female; 181 in IPM plus pest management education group and 180 in pest management education alone group), 334 were included in the primary analysis. For the primary outcome, there was no statistically significant between-group difference for maximal symptom days across 6, 9, and 12 months with a median of 2.0 (interquartile range, 0.7-4.7) maximal symptom days in the IPM plus pest management education group and 2.7 (interquartile range, 1.3-5.0) maximal symptom days in the pest management education alone group (P = .16) and a ratio of symptom frequencies of 0.86 (95% CI, 0.69-1.06). Among mouse-sensitized and exposed children and adolescents with asthma, an intensive year-long integrated pest management intervention plus pest management education vs pest management education alone resulted in no significant difference in maximal symptom days from 6 to 12 months. clinicaltrials.gov Identifier: NCT01251224.

Phospholipase A2 in experimental allergic bronchitis: a lesson from mouse and rat models.

PubMed

Mruwat, Rufayda; Yedgar, Saul; Lavon, Iris; Ariel, Amiram; Krimsky, Miron; Shoseyov, David

2013-01-01

Phospholipases A2 (PLA2) hydrolyzes phospholipids, initiating the production of inflammatory lipid mediators. We have previously shown that in rats, sPLA2 and cPLA2 play opposing roles in the pathophysiology of ovalbumin (OVA)-induced experimental allergic bronchitis (OVA-EAB), an asthma model: Upon disease induction sPLA2 expression and production of the broncho-constricting CysLTs are elevated, whereas cPLA2 expression and the broncho-dilating PGE2 production are suppressed. These were reversed upon disease amelioration by treatment with an sPLA2 inhibitor. However, studies in mice reported the involvement of both sPLA2 and cPLA2 in EAB induction. To examine the relevance of mouse and rat models to understanding asthma pathophysiology. OVA-EAB was induced in mice using the same methodology applied in rats. Disease and biochemical markers in mice were compared with those in rats. As in rats, EAB in mice was associated with increased mRNA of sPLA2, specifically sPLA2gX, in the lungs, and production of the broncho-constricting eicosanoids CysLTs, PGD2 and TBX2 in bronchoalveolar lavage (BAL). In contrast, EAB in mice was associated also with elevated cPLA2 mRNA and PGE2 production. Yet, treatment with an sPLA2 inhibitor ameliorated the EAB concomitantly with reverting the expression of both cPLA2 and sPLA2, and eicosanoid production. In both mice and rats sPLA2 is pivotal in OVA-induced EAB. Yet, amelioration of asthma markers in mouse models, and human tissues, was observed also upon cPLA2 inhibition. It is plausible that airway conditions, involving multiple cell types and organs, require the combined action of more than one, essential, PLA2s.

Th2 LCR is essential for regulation of Th2 cytokine genes and for pathogenesis of allergic asthma.

PubMed

Koh, Byung Hee; Hwang, Soo Seok; Kim, Joo Young; Lee, Wonyong; Kang, Min-Jong; Lee, Chun Geun; Park, Jung-Won; Flavell, Richard A; Lee, Gap Ryol

2010-06-08

Previous studies have shown that Th2 cytokine genes on mouse chromosome 11 are coordinately regulated by the Th2 locus control region (LCR). To examine the in vivo function of Th2 LCR, we generated CD4-specific Th2 LCR-deficient (cLCR KO) mice using Cre-LoxP recombination. The number of CD4 T cells in the cLCR KO mouse was comparable to that in wild-type mice. The expression of Th2 cytokines was dramatically reduced in in vitro-stimulated naïve CD4 T cells. Deletion of the LCR led to a loss of general histone H3 acetylation and histone H3-K4 methylation, and demethylation of DNA in the Th2 cytokine locus. Upon ovalbumin challenge in the mouse model of allergic asthma, cLCR KO mice exhibited marked reduction in the recruitment of eosinophils and lymphocytes in the bronchoalveolar lavage fluid, serum IgE level, lung airway inflammation, mucus production in the airway walls, and airway hyperresponsiveness. These results directly demonstrate that the Th2 LCR is critically important in the regulation of Th2 cytokine genes, in chromatin remodeling of the Th2 cytokine locus, and in the pathogenesis of allergic asthma.

Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneider, Brent C.; Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037; Constant, Stephanie L.

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory responsemore » in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr(VI) may augment severity and alter phenotype of ongoing allergic asthma.« less

Inhibition of TRPC3 downregulates airway hyperresponsiveness, remodeling of OVA-sensitized mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lingwei; Li, Jie; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou

Airway hyperresponsiveness (AHR), airway remodeling and inflammation are the fundamental pathological alterations that occur in asthma. Transient receptor potential canonical 3 (TRPC3) has been implicated in diverse functions of airway smooth muscle cells (ASMCs) in asthma. However, the underlying mechanisms remain incompletely understood. We investigated the mRNA and protein expression of TRPC3 in ASMCs from normal and OVA-sensitized mouse. And the effects of inhibition or knockdown of TRPC3 with Ethyl-1- (4- (2,3,3-trichloroacrylamide) phenyl) −5 - (trifluoromethyl) -1H -pyrazole -4-carboxylate (Pyr3) and lentiviral shRNA on OVA-sensitized mouse AHR, airway remodeling, circulating inflammatory cytokines, cell proliferation and migration. We found that TRPC3 mRNAmore » and protein expression levels were significantly increased in ASMCs from OVA-sensitized mouse. Inhibiting TRPC3 with continuous subcutaneous administration of Pyr3 decreased enhanced pause (Penh) of OVA-sensitized mouse. Meanwhile, both Pyr3 and lentiviral shRNA treatment of ASMCs in OVA-sensitized mouse significantly decreased their proliferation and migration. These results suggest that TRPC3 plays a critical role in asthma and represents a promising new target for asthma treatment. - Highlights: • Penh, airway remodeling and the gene expression and protein of TRPC3 are increased in OVA-sensitized mice. • Inhibition of TRPC3 suppresses the OVA-sensitized mice Penh and airway remodeling. • Inhibition of TRPC3 decreases OVA-sensitized mice ASMC proliferation and migration.« less

1′-Acetoxychavicol Acetate Isolated from Alpinia galanga Ameliorates Ovalbumin-Induced Asthma in Mice

PubMed Central

Park, Sang-Joon; Lee, Eun-Ji; Lee, Jong-Hwa; Han, Sang-Seop; Pyo, Byeong Sik; Park, Dae-Hun; Kim, Bong-Hee

2013-01-01

The World Health Organization reports that 235 million people are currently affected by asthma. This disease is associated with an imbalance of Th1 and Th2 cells, which results in the upregulation of cytokines that promote chronic inflammation of the respiratory system. The inflammatory response causes airway obstruction and can ultimately result in death. In this study we evaluated the effect of 1′-acetoxychavicol acetate (ACA) isolated from Alpinia galanga rhizomes in a mouse model of ovalbumin (OVA)-induced asthma. To generate the mouse model, BALB/c mice were sensitized by intraperitoneal injection of OVA and then challenged with OVA inhalation for 5 days. Mice in the vehicle control group were sensitized with OVA but not challenged with OVA. Treatment groups received dexamethasone, 25 mg/kg/day ACA, or 50 mg/kg/day ACA for 5 days. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. Our results showed that ACA reduced the infiltration of white blood cells (especially eosinophils) and the level of IgE in the lungs of mice challenged with OVA and suppressed histopathological changes such as airway remodeling, goblet-cell hyperplasia, eosinophil infiltration, and glycoprotein secretion. In addition, ACA inhibited expression of the Th2 cytokines interleukin (IL)-4 and IL-13, and Th1 cytokines IL-12α and interferon-γ. Because asthmatic reactions are mediated by diverse immune and inflammatory pathways, ACA shows promise as an antiasthmatic drug candidate. PMID:23451048

Additive Effect of Diesel Exhaust Particulates and Ozone on Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

PubMed Central

Choi, Inseon-S; Takizawa, Hajime; Rhim, TaiYoun; Lee, June-Hyuk; Park, Sung-Woo; Park, Choon-Sik

2005-01-01

Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (Penh) was measured. Levels of IL-4 and IFN-γ were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher Penh than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-γ were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-γ suggesting that DEP amplify Th2 immune response. PMID:16224148

Evaluation of propolis, honey, and royal jelly in amelioration of peripheral blood leukocytes and lung inflammation in mouse conalbumin-induced asthma model

PubMed Central

El-Aidy, Waleed K.; Ebeid, Ahmad A.; Sallam, Abd El-Raouf M.; Muhammad, Ibrahim E.; Abbas, Ayman T.; Kamal, M.A.; Sohrab, Sayed Sartaj

2014-01-01

Bee products have been used since ancient times to treat many diseases, including respiratory ailments. The present study aimed to examine the modulatory effect of honey, royal jelly, and propolis extract on peripheral blood leukocytes and lung inflammation in a mouse conalbumin-induced asthma model. The mice in group I were not sensitised or treated; they were kept as controls. The mice in group II were sensitised and challenged with conalbumin. Twenty-four hours after the first challenge with antigen, the mice in group III received 0.5 mg/kg of dexamethasone intraperitoneally per day for 18 consecutive days and kept as positive controls. The mice in groups IV, V, and VI received 650, 1000, and 30 mg/kg of honey, royal jelly, and propolis (aqueous and ethanolic extract), respectively, once per day for 18 consecutive days. Blood was collected from all of the mice for white blood cell differentiation, and the lungs were removed for histopathological studies. The groups treated with propolis extract exhibited considerable ameliorative effects against asthma, which might be explained by the flavonoids and phenolics found in propolis, which might have antioxidative effects. Otherwise, the sensitised and honey- or royal jelly-treated groups exhibited an increased incidence of asthma cascade events due to increased inflammatory cells. These results might be due to the immunostimulatory and vasodilatory effects of royal jelly and honey, which are antagonistic to bronchial asthma cases. Histopathological examination revealed that the sensitised treated propolis extract groups had significant decreases in inflammatory scores compared with other treatments and the sensitised untreated group. These results confirmed the previous data of peripheral blood cells. PMID:26587007

Glutathione redox regulates airway hyperresponsiveness and airway inflammation in mice.

PubMed

Koike, Yoko; Hisada, Takeshi; Utsugi, Mitsuyoshi; Ishizuka, Tamotsu; Shimizu, Yasuo; Ono, Akihiro; Murata, Yukie; Hamuro, Junji; Mori, Masatomo; Dobashi, Kunio

2007-09-01

Glutathione is the major intracellular redox buffer. We have shown that glutathione redox status, which is the balance between intracellular reduced (GSH) and oxidized (GSSG) glutathione, in antigen-presenting cells (APC) regulates the helper T cell type 1 (Th1)/Th2 balance due to the production of IL-12. Bronchial asthma is a typical Th2 disease. Th2 cells and Th2 cytokines are characteristic of asthma and trigger off an inflammation. Accordingly, we studied the effects of the intracellular glutathione redox status on airway hyperresponsiveness (AHR) and allergen-induced airway inflammation in a mouse model of asthma. We used gamma-Glutamylcysteinylethyl ester (gamma-GCE), which is a membrane-permeating GSH precursor, to elevate the intracellular GSH level and GSH/GSSG ratio of mice. In vitro, gamma-GCE pretreatment of human monocytic THP-1 cells elevated the GSH/GSSG ratio and enhanced IL-12(p70) production induced by LPS. In the mouse asthma model, intraperitoneal injection of gamma-GCE elevated the GSH/GSSG ratio of lung tissue and reduced AHR. gamma-GCE reduced levels of IL-4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it enhanced the production of IL-12 and IFN-gamma. Histologically, gamma-GCE suppressed eosinophils infiltration. Interestingly, we also found that gamma-GCE directly inhibited chemokine-induced eosinophil chemotaxis without affecting eotaxin receptor chemokine receptor 3 (CCR3) expressions. Taken together, these findings suggest that changing glutathione redox balance, increase in GSH level, and the GSH/GSSG ratio by gamma-GCE, ameliorate bronchial asthma by altering the Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine production and eosinophil migration itself.

Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma.

PubMed

Kim, Dong Eon; Lee, Yonghyun; Kim, MinGyo; Lee, Soyoung; Jon, Sangyong; Lee, Seung-Hyo

2017-09-01

Although asthma, a chronic inflammatory airway disease, is relatively well-managed by inhaled corticosteroids, the side effects associated with the long-term use of these agents precipitate the need for alternative therapeutic options based on differing modes of action. Bilirubin, a potent endogenous antioxidant, and anti-inflammatory molecule have been shown to ameliorate asthmatic symptoms; however, its clinical translation has been limited owing to its water insolubility and associated potential toxicity. Here we report the first application of bilirubin-based nanoparticles (BRNPs) as a nanomedicine for the treatment of allergic lung inflammatory disease. BRNPs were prepared directly from self-assembly of PEGylated bilirubin in aqueous solution and had a hydrodynamic diameter of ∼100 nm. Because allergen-specific type 2 T-helper (Th2) cells play a key role in the pathogenesis and progression of allergic asthma, the effects of BRNPs on Th2 immune responses were investigated both in vivo and in vitro. BRNPs after intravenous injection (i.v.) showed much higher serum concentration and a longer circulation time of bilirubin than the intraperitoneal injection (i.p.) of BRNPs or unconjugated bilirubin (UCB). The anti-asthmatic effects of BRNPs were assessed in a mouse model of allergen-induced asthma. Compared with UCB, treatment with BRNPs suppressed the symptoms of experimental allergic asthma and dramatically ameliorated Th2-related allergic lung inflammation. Consistent with these results, BRNPs caused a reduction of Th2 cell populations and the expression of related cytokines by antibody-stimulated CD4 + T cells in vitro. Therefore, our results establish BRNPs as an important immunomodulatory agent that may be useful as a therapeutic for allergic lung inflammatory disease and other immune-mediated disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of propolis, honey, and royal jelly in amelioration of peripheral blood leukocytes and lung inflammation in mouse conalbumin-induced asthma model.

PubMed

El-Aidy, Waleed K; Ebeid, Ahmad A; Sallam, Abd El-Raouf M; Muhammad, Ibrahim E; Abbas, Ayman T; Kamal, M A; Sohrab, Sayed Sartaj

2015-11-01

Bee products have been used since ancient times to treat many diseases, including respiratory ailments. The present study aimed to examine the modulatory effect of honey, royal jelly, and propolis extract on peripheral blood leukocytes and lung inflammation in a mouse conalbumin-induced asthma model. The mice in group I were not sensitised or treated; they were kept as controls. The mice in group II were sensitised and challenged with conalbumin. Twenty-four hours after the first challenge with antigen, the mice in group III received 0.5 mg/kg of dexamethasone intraperitoneally per day for 18 consecutive days and kept as positive controls. The mice in groups IV, V, and VI received 650, 1000, and 30 mg/kg of honey, royal jelly, and propolis (aqueous and ethanolic extract), respectively, once per day for 18 consecutive days. Blood was collected from all of the mice for white blood cell differentiation, and the lungs were removed for histopathological studies. The groups treated with propolis extract exhibited considerable ameliorative effects against asthma, which might be explained by the flavonoids and phenolics found in propolis, which might have antioxidative effects. Otherwise, the sensitised and honey- or royal jelly-treated groups exhibited an increased incidence of asthma cascade events due to increased inflammatory cells. These results might be due to the immunostimulatory and vasodilatory effects of royal jelly and honey, which are antagonistic to bronchial asthma cases. Histopathological examination revealed that the sensitised treated propolis extract groups had significant decreases in inflammatory scores compared with other treatments and the sensitised untreated group. These results confirmed the previous data of peripheral blood cells.

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

PubMed Central

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-01-01

Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system. PMID:16930490

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

PubMed

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-08-24

Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system.

A novel (S)-(+)-decursin derivative, (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano[3,2-g]chromen-3-yl-ester, inhibits ovalbumin-induced lung inflammation in a mouse model of asthma.

PubMed

Yang, Eun Ju; Song, Gyu-Yong; Lee, Ji-Sook; Yun, Chi-Young; Kim, In Sik

2009-03-01

(S)-(+)-Decursin is a coumarin compound present in herbal extracts that has various biological activities. (S)-(+)-Decursin attenuates pathophysiologic progression in cancer, bacterial infection and neuropathy. Asthma is an inflammatory disease associated with increased infiltration of leukocytes, especially eosinophils, and secretion of mucus into the airways. Although (S)-(+)-decursin, as well as (S)-(+)-decursin analogues, have various pharmacological properties, the effect of these compounds on asthma is not known. In the present study, we synthesized (S)-(+)-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano[3,2-g]chromen-3-yl-ester (compound 6, C6) from (S)-(+)-decursin and examined if C6 had any inhibitory effects on lung inflammation in a mouse model of ovalbumin-induced asthma. C6 significantly inhibited the leukocytosis (p < 0.01) and eosinophilia (p < 0.05) in bronchoalveolar lavage (BAL) fluid. Examination of lung tissues stained with hematoxylin and eosin and periodic acid Schiff reagents showed that C6 suppressed the increased infiltration of inflammatory cells and elevated mucus hypersecretion. Protein levels of interleukin (IL)-5 (p < 0.05) and eotaxin (p < 0.01) were significantly reduced in BAL fluid by C6. C6 also significantly reduced total and ovalbumin-specific immunoglobulin E (IgE) levels in BAL fluid (p < 0.01) as well as that in serum (p < 0.05). C6 may have pharmacological effects for asthma and may be a potent therapeutic agent for the treatment of allergic airway diseases.

Anti-inflammatory effects of tilmicosin in a noninfectious mouse model of allergic asthma.

PubMed

Ci, Xinxin; Chu, Xiao; Xiang, Hua; Li, Xiangchao; Deng, Xuming

2011-12-01

Tilmicosin, a semi-synthetic tylosin-derived macrolide antibiotic commonly used by veterinarians, has been shown to possess anti-inflammatory activity. However, possible use in asthma treatment has not yet been studied. In this study, we investigated the anti-inflammatory properties of tilmicosin using a murine asthma model. BALB/c mice were sensitized and challenged by intraperitoneal (i.p.) or nasal administration of ovalbumin. Tilmicosin (10 and 20 mg/kg) treatment resulted in a marked reduction in the presence of several types of immune cells and cytokines in the bronchoalveolar lavage fluids of mice. Levels of ovalbumin-specific Immunoglobulin E (IgE) were significantly decreased following treatment with tilmicosin (10 and 20 mg/kg). Histological studies using H&E (haematoxylin and eosin) and AB-PAS (alcian blue-periodic acid-Schiff) staining demonstrated that tilmicosin substantially inhibited both ovalbumin-induced inflammatory cells in lung tissues and goblet cell hyperplasia in the airway. These findings provided new insight into the immunopharmacological role of tilmicosin in terms of its effects in a murine model of asthma.

A Recombinant DNA Plasmid Encoding the sIL-4R-NAP Fusion Protein Suppress Airway Inflammation in an OVA-Induced Mouse Model of Asthma.

PubMed

Liu, Xin; Fu, Guo; Ji, Zhenyu; Huang, Xiabing; Ding, Cong; Jiang, Hui; Wang, Xiaolong; Du, Mingxuan; Wang, Ting; Kang, Qiaozhen

2016-08-01

Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail. To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R.

Human sera IgE reacts with a Metarhizium anisopliae fungal catalase

EPA Science Inventory

Background: Previous studies have demonstrated that Metarhzium anisopliae extract can induce immune responses in a mouse model that are characteristic of human allergic asthma. Objectives: The objective of this study was to identify and characterize the extract proteins t...

Biomarkers of Disease and Treatment in Murine and Cynomolgus Models of Chronic Asthma

PubMed Central

Louten, Jennifer; Mattson, Jeanine D.; Malinao, Maria-Christina; Li, Ying; Emson, Claire; Vega, Felix; Wardle, Robert L.; Van Scott, Michael R.; Fick, Robert B.; McClanahan, Terrill K.; de Waal Malefyt, Rene; Beaumont, Maribel

2012-01-01

Background Biomarkers facilitate early detection of disease and measurement of therapeutic efficacy, both at clinical and experimental levels. Recent advances in analytics and disease models allow comprehensive screening for biomarkers in complex diseases, such as asthma, that was previously not feasible. Objective Using murine and nonhuman primate (NHP) models of asthma, identify biomarkers associated with early and chronic stages of asthma and responses to steroid treatment. Methods The total protein content from thymic stromal lymphopoietin transgenic (TSLP Tg) mouse BAL fluid was ascertained by shotgun proteomics analysis. A subset of these potential markers was further analyzed in BAL fluid, BAL cell mRNA, and lung tissue mRNA during the stages of asthma and following corticosteroid treatment. Validation was conducted in murine and NHP models of allergic asthma. Results Over 40 proteins were increased in the BAL fluid of TSLP Tg mice that were also detected by qRT-PCR in lung tissue and BAL cells, as well as in OVA-sensitive mice and house dust mite-sensitive NHP. Previously undescribed as asthma biomarkers, KLK1, Reg3γ, ITLN2, and LTF were modulated in asthmatic mice, and Clca3, Chi3l4 (YM2), and Ear11 were the first lung biomarkers to increase during disease and the last biomarkers to decline in response to therapy. In contrast, GP-39, LCN2, sICAM-1, YM1, Epx, Mmp12, and Klk1 were good indicators of early therapeutic intervention. In NHP, AMCase, sICAM-1, CLCA1, and GP-39 were reduced upon treatment with corticosteroids. Conclusions and clinical relevance These results significantly advance our understanding of the biomarkers present in various tissue compartments in animal models of asthma, including those induced early during asthma and modulated with therapeutic intervention, and show that BAL cells (or their surrogate, induced sputum cells) are a viable choice for biomarker examination. PMID:22837640

The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

PubMed

Reznikov, Leah R; Meyerholz, David K; Abou Alaiwa, Mahmoud H; Kuan, Shin-Ping; Liao, Yan-Shin J; Bormann, Nicholas L; Bair, Thomas B; Price, Margaret; Stoltz, David A; Welsh, Michael J

2018-04-05

Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity. As a comparison, we also utilized previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating airway hyperreactivity; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma.

PubMed

Liu, Chentao; Huang, Rong; Yao, Rujie; Yang, Aimei

2017-10-01

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Recurrent respiratory tract infections in young children, especially viral infections, are the major cause of acute asthmatic exacerbations and contribute to development of asthma. Bacterial extracts have been used to improve the immune defenses of the respiratory tract. However, seldom studies have examined the effect of bacterial lysates on childhood asthma. In this study, we examined whether bacterial lysates (OM-85) will improve symptoms of asthmatic mice via modulation of the immune response. Asthmatic mice models were established with OVA challenge and treated with oral administration of Broncho-Vaxom (OM-85). Next, infiltrations of inflammatory cells including eosinophil and neutrophils were examined. Pulmonary tissues in asthmatic mice models were analyzed by hematoxylin and eosin (HE) staining. The levels of Th1/Th2-typed cytokines in bronchoalveolar lavage fluid (BALF) of asthmatic mice models were examined by enzyme-linked immunosorbent assay. Compared to control group, we found significant reduction of airway wall thickness, luminal stenosis, and mucus plug formation in asthmatic mice models after oral administration of OM-85. The infiltrations of eosinophil were also significantly decreased in BALF in asthmatic mice models. Oral administration of OM-85 was shown to suppress Th2-type cytokine levels. Our findings provide evidence that oral administration of OM-85 is capable of attenuating airway inflammation in asthmatic mice models. Oral administration of OM-85 may have a positive impact in terms of asthma severity.

AN EXTRACT OF PENICILLIUM CHRYSOGENUM INDUCES DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES IN MICE

EPA Science Inventory

Rationale: Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typ...

DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BALB/MICE

EPA Science Inventory

Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

Differential Allergy Induction by Molds Found in Water-Damaged Homes

EPA Science Inventory

Abstract: We compared the allergy induction potential of high concentration molds found in water-damaged homes and molds found more universally to house dust mite (HDM) in our mouse allergy/asthma model. Female BALB/c mice received 1 or 4 exposures by intratracheal aspiration of ...

ASTHMATIC HUMAN SERUM IGE-REACTIVITY WITH MOLD EXTRACTS

EPA Science Inventory

Although molds have demonstrated the ability to induce allergic asthma-like responses in mouse models, their role in human disease is unclear. This study was undertaken to provide insight into the prevalence of human IgE-reactivity and identify the target mold protein(s). The st...

Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

PubMed

Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

2017-12-01

This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

Comparative immunology of allergic responses.

PubMed

Gershwin, Laurel J

2015-01-01

Allergic responses occur in humans, rodents, non-human primates, avian species, and all of the domestic animals. These responses are mediated by immunoglobulin E (IgE) antibodies that bind to mast cells and cause release/synthesis of potent mediators. Clinical syndromes include naturally occurring asthma in humans and cats; atopic dermatitis in humans, dogs, horses, and several other species; food allergies; and anaphylactic shock. Experimental induction of asthma in mice, rats, monkeys, sheep, and cats has helped to reveal mechanisms of pathogenesis of asthma in humans. All of these species share the ability to develop a rapid and often fatal response to systemic administration of an allergen--anaphylactic shock. Genetic predisposition to development of allergic disease (atopy) has been demonstrated in humans, dogs, and horses. Application of mouse models of IgE-mediated allergic asthma has provided evidence for a role of air pollutants (ozone, diesel exhaust, environmental tobacco smoke) in enhanced sensitization to allergens.

Allergic Responses Induced by a Fungal Biopesticide Metarhizium anisopliae and House Dust Mite are Compared in a Mouse Model

EPA Science Inventory

Biopesticides can be effective in controlling their target pest. However, research regarding mammalian health impacts of these agents has focused on toxicity and pathogenicity, with limited research regarding allergenicity and asthma development. We compared the ability of funga...

The relative allergenicity of Stachybotrys chartarum compared to house dust mite extracts in a mouse model

EPA Science Inventory

A report by the Institute of Medicine suggested that more research is needed to better understand mold effects on allergic disease, particularly asthma development. The authors compared the ability of the fungus Stachybotrys chartarum (SCE) and house dust mite (HDM) extracts to i...

Assessing the Allergenic Potential of Molds Found in Water-Damaged Homes in a Mouse Model

EPA Science Inventory

Damp/moldy indoor environments, which have resulted from flooding events and may increase as a result of climate change, have been associated with asthma exacerbation. Certain molds found in significantly higher or lower concentrations in asthmatics’ homes compared to control ho...

DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BAL/C MICE

EPA Science Inventory

Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

A 4-Week Model of House Dust Mite (HDM) Induced Allergic Airways Inflammation with Airway Remodeling.

PubMed

Woo, L N; Guo, W Y; Wang, X; Young, A; Salehi, S; Hin, A; Zhang, Y; Scott, J A; Chow, C W

2018-05-02

Animal models of allergic airways inflammation are useful tools in studying the pathogenesis of asthma and potential therapeutic interventions. The different allergic airways inflammation models available to date employ varying doses, frequency, duration and types of allergen, which lead to the development of different features of asthma; showing varying degrees of airways inflammation and hyper-responsiveness (AHR) and airways remodeling. Models that also exhibit airway remodeling, a key feature of asthma, in addition to AHR and airway inflammation typically require 5-12 weeks to develop. In this report, we describe a 4-week mouse model of house dust mite (HDM)-induced allergic airways inflammation, and compare the phenotypic features of two different doses of HDM exposures (10 µg and 25 µg) for 5 days/week with a well-characterized 8-week chronic HDM model. We found that 4 weeks of intranasal HDM (25 µg in 35 µl saline; 5 days/week) resulted in AHR, airway inflammation and airway remodeling that were comparable to the 8-week model. We conclude that this new 4-week HDM model is another useful tool in studies of human asthma that offers advantages of shorter duration for development and decreased costs when compared to other models that require longer durations of exposure (5-12 weeks) to develop.

Immune Response to Human Metapneumovirus Infection: What We Have Learned from the Mouse Model

PubMed Central

Cheemarla, Nagarjuna R.; Guerrero-Plata, Antonieta

2015-01-01

Human Metapneumovirus (hMPV) is a leading respiratory viral pathogen associated with bronchiolitis, pneumonia, and asthma exacerbation in young children, the elderly and immunocompromised individuals. The development of a potential vaccine against hMPV requires detailed understanding of the host immune system, which plays a significant role in hMPV pathogenesis, susceptibility and vaccine efficacy. As a result, animal models have been developed to better understand the mechanisms by which hMPV causes disease. Several animal models have been evaluated and established so far to study the host immune responses and pathophysiology of hMPV infection. However, inbred laboratory mouse strains have been one of the most used animal species for experimental modeling and therefore used for the studies of immunity and immunopathogenesis to hMPV. This review summarizes the contributions of the mouse model to our understanding of the immune response against hMPV infection. PMID:26393657

Immune Response to Human Metapneumovirus Infection: What We Have Learned from the Mouse Model.

PubMed

Cheemarla, Nagarjuna R; Guerrero-Plata, Antonieta

2015-09-18

Human Metapneumovirus (hMPV) is a leading respiratory viral pathogen associated with bronchiolitis, pneumonia, and asthma exacerbation in young children, the elderly and immunocompromised individuals. The development of a potential vaccine against hMPV requires detailed understanding of the host immune system, which plays a significant role in hMPV pathogenesis, susceptibility and vaccine efficacy. As a result, animal models have been developed to better understand the mechanisms by which hMPV causes disease. Several animal models have been evaluated and established so far to study the host immune responses and pathophysiology of hMPV infection. However, inbred laboratory mouse strains have been one of the most used animal species for experimental modeling and therefore used for the studies of immunity and immunopathogenesis to hMPV. This review summarizes the contributions of the mouse model to our understanding of the immune response against hMPV infection.

Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.

PubMed

Alrifai, Mohammed; Marsh, Leigh M; Dicke, Tanja; Kılıç, Ayse; Conrad, Melanie L; Renz, Harald; Garn, Holger

2014-01-01

Allergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investigated the dynamics of airway remodelling and repair in an experimental asthma model and studied how pharmacological intervention affects these processes. Using BALB/c mice, the kinetics of chronic asthma progression and resolution were characterised in absence and presence of inhaled corticosteroid (ICS) treatment. Airway inflammation and remodelling was assessed by the analysis of bronchoalveolar and peribronichal inflammatory cell infiltrate, goblet cell hyperplasia, collagen deposition and smooth muscle thickening. Chronic allergen exposure resulted in early (goblet cell hyperplasia) and late remodelling (collagen deposition and smooth muscle thickening). After four weeks of allergen cessation eosinophilic inflammation, goblet cell hyperplasia and collagen deposition were resolved, full resolution of lymphocyte inflammation and smooth muscle thickening was only observed after eight weeks. ICS therapy when started before the full establishment of chronic asthma reduced the development of lung inflammation, decreased goblet cell hyperplasia and collagen deposition, but did not affect smooth muscle thickening. These effects of ICS on airway remodelling were maintained for a further four weeks even when therapy was discontinued. Utilising a chronic model of experimental asthma we have shown that repeated allergen exposure induces reversible airway remodelling and inflammation in mice. Therapeutic intervention with ICS was partially effective in inhibiting the transition from acute to chronic asthma by reducing airway inflammation and remodelling but was ineffective in preventing smooth muscle hypertrophy.

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy.

PubMed

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-06-01

Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Allergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment. In atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

PubMed Central

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-01-01

Purpose of review Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Recent findings Allergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment. Summary In atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles. PMID:28375932

Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation

PubMed Central

2013-01-01

Background This study investigates the effect of Xiao-Qing-Long-Tang (XQLT) on neurotrophin in an established mouse model of Dermatophagoides pteronyssinus (Der p)-induced acute allergic asthma and in a LA4 cell line model of lung adenoma. The effects of XQLT on the regulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), airway hyper-responsiveness (AHR) and immunoglobulin E were measured. Methods LA4 cells were stimulated with 100 μg/ml Der p 24 h and the supernatant was collected for ELISA analysis. Der p-stimulated LA4 cells with either XQLT pre-treatment or XQLT co-treatment were used to evaluate the XQLT effect on neurotrophin. Balb/c mice were sensitized on days 0 and 7 with a base-tail injection of 50 μg Dermatophagoides pteronyssinus (Der p) that was emulsified in 50 μl incomplete Freund’s adjuvant (IFA). On day 14, mice received an intra-tracheal challenge of 50 μl Der p (2 mg/ml). XQLT (1g/Kg) was administered orally to mice either on days 2, 4, 6, 8, 10 and 12 as a preventive strategy or on day 15 as a therapeutic strategy. Results XQLT inhibited expression of those NGF, BDNF and thymus-and activation-regulated cytokine (TARC) in LA4 cells that were subjected to a Der p allergen. Both preventive and therapeutic treatments with XQLT in mice reduced AHR. Preventive treatment with XQLT markedly decreased NGF in broncho-alveolar lavage fluids (BALF) and BDNF in serum, whereas therapeutic treatment reduced only serum BDNF level. The reduced NGF levels corresponded to a decrease in AHR by XQLT treatment. Reduced BALF NGF and TARC and serum BDNF levels may have been responsible for decreased eosinophil infiltration into lung tissue. Immunohistochemistry showed that p75NTR and TrkA levels were reduced in the lungs of mice under both XQLT treatment protocols, and this reduction may have been correlated with the prevention of the asthmatic reaction by XQLT. Conclusion XQLT alleviated allergic inflammation including AHR, IgE elevation and eosinophil infiltration in Der p stimulated mice by regulating neurotrophin and reducing TARC. These results revealed the potential pharmacological targets on which the XQLT decotion exerts preventive and therapeutic effects in an allergic asthma mouse model. PMID:24010817

Interaction between allergic asthma and atherosclerosis

PubMed Central

Liu, Conglin; Zhang, Jingying; Shi, Guo-Ping

2015-01-01

Prior studies have established an essential role of mast cells in allergic asthma and atherosclerosis. Mast cell deficiency or inactivation protects mice from allergen-induced airway hyper-responsiveness and diet-induced atherosclerosis, suggesting that mast cells share pathologic activities in both diseases. Allergic asthma and atherosclerosis are inflammatory diseases that contain similar sets of elevated numbers of inflammatory cells in addition to mast cells in the airway and arterial wall, such as macrophages, monocytes, T cells, eosinophils, and smooth muscle cells. Emerging evidence from experimental models and human studies points to a potential interaction between the two seemingly unrelated diseases. Patients or mice with allergic asthma have a high risk of developing atherosclerosis or vice versa, despite the fact that asthma is a Th2-oriented disease, whereas Th1 immunity promotes atherosclerosis. In addition to the preferred Th1/Th2 responses that may differentiate the two diseases, mast cells and many other inflammatory cells also contribute to their pathogenesis by much more than just T cell immunity. Here we summarize the different roles of airway and arterial wall inflammatory cells and vascular cells in asthma and atherosclerosis, and propose an interaction between the two diseases, although limited investigations are available to delineate the molecular and cellular mechanisms by which one disease increases the risk of the other. Results from mouse allergic asthma and atherosclerosis models and from human population studies lead to the hypothesis that patients with atherosclerosis may benefit from anti-asthmatic medications, or that the therapeutic regimens targeting atherosclerosis may also alleviate allergic asthma. PMID:26608212

Comparison of the Allergic Responses Induced by PeniciIlium chrysogenum and House Dust Mite Extracts in a Mouse Model

EPA Science Inventory

A report by the Institute of Medicine suggested that more research is needed to better understand mold effects on allergic disease, particularly asthma development. We compared the ability of the fungal Penicillium chrysogenum (PCE) and house dust mite (HDM) extracts to induce al...

QUALITATIVE MEASUREMENTS OF IGE AND IGG IN HUMAN ASTHMATIC SERUM FOR MOLD REACTIVITY

EPA Science Inventory

Rational: Molds have the ability to induce allergic asthma-like responses in mouse models; however, their role in human disease is unclear. This study was to develop a screening tool for reactivity of human sera to mold extracts by using a minimal amount of sera for a qual...

Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice

USDA-ARS?s Scientific Manuscript database

The effects of fish oil supplements on diminishing airway inflammation in asthma have been studied in mouse models and human intervention trials with varying results. However, the independent effects of the main omega-3 PUFAs found in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (D...

Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma.

PubMed

Macchiaverni, P; Rekima, A; Turfkruyer, M; Mascarell, L; Airouche, S; Moingeon, P; Adel-Patient, K; Condino-Neto, A; Annesi-Maesano, I; Prescott, S L; Tulic, M K; Verhasselt, V

2014-03-01

There is an urgent need to identify environmental risk and protective factors in early life for the prevention of allergy. Our study demonstrates the presence of respiratory allergen from house dust mite, Der p 1, in human breast milk. Der p 1 in milk is immunoreactive, present in similar amounts as dietary egg antigen, and can be found in breast milk from diverse regions of the world. In a mouse model of asthma, oral exposure to Der p through breast milk strongly promotes sensitization rather than protect the progeny as we reported with egg antigen. These data highlight that antigen administration to the neonate through the oral route may contribute to child allergic sensitization and have important implications for the design of studies assessing early oral antigen exposure for allergic disease prevention. The up-to-now unknown worldwide presence of respiratory allergen in maternal milk allows new interpretation and design of environmental control epidemiological studies for allergic disease prevention. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acinetobacter baumannii Infection Inhibits Airway Eosinophilia and Lung Pathology in a Mouse Model of Allergic Asthma

PubMed Central

Qiu, Hongyu; KuoLee, Rhonda; Harris, Greg; Zhou, Hongyan; Miller, Harvey; Patel, Girishchandra B.; Chen, Wangxue

2011-01-01

Allergic asthma is a dysregulation of the immune system which leads to the development of Th2 responses to innocuous antigens (allergens). Some infections and microbial components can re-direct the immune response toward the Th1 response, or induce regulatory T cells to suppress the Th2 response, thereby inhibiting the development of allergic asthma. Since Acinetobacter baumannii infection can modulate lung cellular and cytokine responses, we studied the effect of A. baumannii in modulating airway eosinophilia in a mouse model of allergic asthma. Ovalbumin (OVA)-sensitized mice were treated with live A. baumannii or phosphate buffered saline (PBS), then intranasally challenged with OVA. Compared to PBS, A. baumannii treatment significantly reduced pulmonary Th2 cytokine and chemokine responses to OVA challenge. More importantly, the airway inflammation in A. baumannii-treated mice was strongly suppressed, as seen by the significant reduction of the proportion and the total number of eosinophils in the bronchoalveolar lavage fluid. In addition, A. baumannii-treated mice diminished lung mucus overproduction and pathology. However, A. baumannii treatment did not significantly alter systemic immune responses to OVA. Serum OVA-specific IgE, IgG1 and IgG2a levels were comparable between A. baumannii- and PBS-treated mice, and tracheobronchial lymph node cells from both treatment groups produced similar levels of Th1 and Th2 cytokines in response to in vitro OVA stimulation. Moreover, it appears that TLR-4 and IFN-γ were not directly involved in the A. baumannii-induced suppression of airway eosinophilia. Our results suggest that A. baumannii inhibits allergic airway inflammation by direct suppression of local pulmonary Th2 cytokine responses to the allergen. PMID:21789200

Dysregulation of metabolic pathways in a mouse model of allergic asthma.

PubMed

Quinn, K D; Schedel, M; Nkrumah-Elie, Y; Joetham, A; Armstrong, M; Cruickshank-Quinn, C; Reisdorph, R; Gelfand, E W; Reisdorph, N

2017-09-01

Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function. In this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6 hour, 24 hour, and 48 hour after the last challenge. Samples were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Airway hyper-responsiveness (AHR) measurements and differential cell counts were performed. In total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (P=6.6×10 -5 ), arginine and proline metabolism (P=1.12×10 -7 ), glycerophospholipid metabolism (P=1.3×10 -10 ), and the neurotrophin signaling pathway (P=7.0×10 -6 ). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxylate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia. These findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma

PubMed Central

Ricci, Giampaolo; Astolfi, Annalisa; Remondini, Daniel; Cipriani, Francesca; Formica, Serena; Dondi, Arianna; Pession, Andrea

2011-01-01

Background Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach. Methodology/Principal Findings We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models. Conclusion/Significance Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population. PMID:21359210

No Adjuvant Effect of Bacillus thuringiensis-Maize on Allergic Responses in Mice

PubMed Central

Dekan, Gerhard; Epstein, Michelle M.

2014-01-01

Genetically modified (GM) foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt)-maize (MON810) on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA)-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma. PMID:25084284

Indoor Molds and Respiratory Hypersensitivity: A Comparison of Selected Molds and House Dust Mite Induced Responses in a Mouse Model

EPA Science Inventory

Introduction/Study Goal Molds are ubiquitous in the environment and exposures to molds contribute to various human diseases including allergic lung diseases. The Institute of Medicine reports and WHO gUidelines concluded that the role of molds in asthma induction is not clear bu...

Exposure to triclosan augments the allergic response to ovalbumin in a mouse model of asthma.

PubMed

Anderson, Stacey E; Franko, Jennifer; Kashon, Michael L; Anderson, Katie L; Hubbs, Ann F; Lukomska, Ewa; Meade, B Jean

2013-03-01

During the last decade, there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouthwashes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75 to 3% (0.375-1.5mg/mouse/day) for 28 consecutive days. Concordantly, mice were ip injected with OVA (0.9 µg) and aluminum hydroxide (0.5mg) on days 1 and 10 and challenged with OVA (125 µg) by pharyngeal aspiration on days 19 and 27. Compared with the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, interleukin-13 cytokine levels, and numbers of lung eosinophils were demonstrated when mice were coexposed to OVA and triclosan. Statistically significant increases in OVA-specific and nonspecific airway hyperreactivity were observed for all triclosan coexposed groups compared with the vehicle and OVA controls. In these studies, exposure to triclosan alone was not demonstrated to be allergenic; however, coexposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens.

Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression

PubMed Central

Saravia, Jordy; You, Dahui; Thevenot, Paul; Lee, Greg I.; Shrestha, Bishwas; Lomnicki, Slawo; Cormier, Stephania A.

2013-01-01

Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-life CDPM exposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPM+HDM failed to develop a typical asthma phenotype including airway hyperresponsiveness, Th2-inflammation, Muc5ac expression, eosinophilia, and HDM-specific Ig compared to HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was two-fold higher in CDPM+HDM mice compared to HDM-mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and Tregs, resulting in suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific-antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life. PMID:24172848

Vitamin E antagonizes ozone-induced asthma exacerbation in Balb/c mice through the Nrf2 pathway.

PubMed

Duan, Liju; Li, Jinquan; Ma, Ping; Yang, Xu; Xu, Shunqing

2017-09-01

Millions of people are regularly exposed to ozone, a gas known to contribute significantly to worsening the symptoms of patients with asthma. However, the mechanisms underlying these ozone exacerbation effects are not fully understood. In this study, we examined the exacerbation effect of ozone in OVA-induced asthma mice and tried to demonstrate the protective mechanism of vitamin E (VE). An asthma mouse model was established, and used to identify the exacerbating effects of ozone by assessing cytokine and serum immunoglobulin concentrations, airway leukocyte infiltration, histopathological changes in lung tissues, and airway hyper-responsiveness. We then determined the amount of reactive oxygen species (ROS) accumulated, the extent to which VE induced ROS elimination, and examined the antagonistic effects of VE on the ozone-induced exacerbating effects. This study showed that 1-ppm ozone exposure could exacerbate OVA-induced asthma in mice. More importantly we found that ozone induced oxidative stress in asthmatic airways may lead to the inhibition of Nuclear factor-erythroid 2-related factor 2 (Nrf2), and may subsequently induce even more exaggerated oxidative stress associated with asthma exacerbation. Through VE induced Nrf2 activation and the subsequent increase in Nrf2 target protein expression, this study suggests a novel mechanism for alleviating ozone exacerbated asthma symptoms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice

PubMed Central

Jung, Sun Hee; Kwon, Jang-Mi; Shim, Jae Won; Kim, Deok Soo; Jung, Hye Lim; Park, Moon Soo; Park, Soo-Hee; Lee, Jinmi; Lee, Won-Young

2013-01-01

Purpose Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity. Materials and Methods We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid. Results Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge. Conclusion Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma. PMID:24142648

Advances in asthma in 2016: Designing individualized approaches to management.

PubMed

Anderson, William C; Apter, Andrea J; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2017-09-01

In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Quercetin, kaempferol and isorhamnetin in Elaeagnus pungens Thunb. leaf: pharmacological activities and quantitative determination studies.

PubMed

Zhu, Ji-Xiao; Wen, Le; Zhong, Wei-Jin; Xiong, Li; Liang, Jian; Wang, Hong-Ling

2018-05-26

Elaeagnus pungens (E. pungens) leaf was documented to be very effective to treat asthma and chronic bronchitis both as traditional Chinese medicine and minority traditional medicine; yet the actual effective components still remain unknown. This work is to investigate the anti-inflammatory, antalgic and antitussive activities of E. pungens leaf, quercetin and kaempferol, and their contents in E. pungens leaf. Pharmacological experiments showed they could considerably reduce ear-swelling of mouse and relieve writhing reaction of mouse; they could also prevent mouse from coughing, significantly. These findings suggested quercetin and kaempferol are major effective components treating asthma and chronic bronchitis. Quantitative analysis results indicated the levels of quercetin, kaempferol and isorhamnetin varied greatly in different species of Elaeagnus and in different plant parts: E. pungens leaf is more similar to Elaeagnus umbellate leaf chemically; quercetin level is exceptionally high in Elaeagnus oldhami leaf; E. pungens leaf is a better medical part for treating asthma and chronic bronchitis in comparison with other parts. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Intratracheal instillation of pravastatin for the treatment of murine allergic asthma: a lung-targeted approach to deliver statins

PubMed Central

Zeki, Amir A; Bratt, Jennifer M; Chang, Kevin Y; Franzi, Lisa M; Ott, Sean; Silveria, Mark; Fiehn, Oliver; Last, Jerold A; Kenyon, Nicholas J

2015-01-01

Systemic treatment with statins mitigates allergic airway inflammation, TH2 cytokine production, epithelial mucus production, and airway hyperreactivity (AHR) in murine models of asthma. We hypothesized that pravastatin delivered intratracheally would be quantifiable in lung tissues using mass spectrometry, achieve high drug concentrations in the lung with minimal systemic absorption, and mitigate airway inflammation and structural changes induced by ovalbumin. Male BALB/c mice were sensitized to ovalbumin (OVA) over 4 weeks, then exposed to 1% OVA aerosol or filtered air (FA) over 2 weeks. Mice received intratracheal instillations of pravastatin before and after each OVA exposure (30 mg/kg). Ultra performance liquid chromatography – mass spectrometry was used to quantify plasma, lung, and bronchoalveolar lavage fluid (BALF) pravastatin concentration. Pravastatin was quantifiable in mouse plasma, lung tissue, and BALF (BALF > lung > plasma for OVA and FA groups). At these concentrations pravastatin inhibited airway goblet cell hyperplasia/metaplasia, and reduced BALF levels of cytokines TNFα and KC, but did not reduce BALF total leukocyte or eosinophil cell counts. While pravastatin did not mitigate AHR, it did inhibit airway hypersensitivity (AHS). In this proof-of-principle study, using novel mass spectrometry methods we show that pravastatin is quantifiable in tissues, achieves high levels in mouse lungs with minimal systemic absorption, and mitigates some pathological features of allergic asthma. Inhaled pravastatin may be beneficial for the treatment of asthma by having direct airway effects independent of a potent anti-inflammatory effect. Statins with greater lipophilicity may achieve better anti-inflammatory effects warranting further research. PMID:25969462

Distribution and determinants of mouse allergen exposure in low-income New York City apartments.

PubMed Central

Chew, Ginger L; Perzanowski, Matthew S; Miller, Rachel L; Correa, Juan C; Hoepner, Lori A; Jusino, Carlos M; Becker, Mark G; Kinney, Patrick L

2003-01-01

Previous studies of mouse allergens and laboratory-animal-worker-related allergy and asthma suggest that quantifying mouse allergen levels in homes could augment our understanding of inner-city asthma. We hypothesized that levels of mouse allergen in inner-city homes would be related to certain household characteristics. Dust samples were collected from the kitchens and beds of 221 mothers enrolled in a prospective birth cohort study, 92 of African American and 129 of Dominican ethnicity. Samples were analyzed for mouse urinary protein. The geometric mean for kitchen samples was 4.6 micro g/g [95% confidence interval (95% CI), 3.2-6.5] and for bed samples was 0.9 micro g/g (95% CI, 0.8-1.1). The variables associated with mouse allergen levels in the home were frequency of mouse sightings, use of traps or pesticides for mice, presence of holes in ceilings or walls, absence of a cat, and living in a building with fewer than eight floors. Statistically significant neighborhood differences in levels of mouse allergen and report of rodents in the home were also observed. In conclusion, mouse allergen was prevalent among inner-city apartments, and the positive predictive value of self-reported frequent mouse sightings was high (90% for kitchens). However, high levels of mouse allergen were also found in many homes where mothers reported never seeing mice. PMID:12896857

Role for NLRP3 Inflammasome-mediated, IL-1β-Dependent Responses in Severe, Steroid-Resistant Asthma.

PubMed

Kim, Richard Y; Pinkerton, James W; Essilfie, Ama T; Robertson, Avril A B; Baines, Katherine J; Brown, Alexandra C; Mayall, Jemma R; Ali, M Khadem; Starkey, Malcolm R; Hansbro, Nicole G; Hirota, Jeremy A; Wood, Lisa G; Simpson, Jodie L; Knight, Darryl A; Wark, Peter A; Gibson, Peter G; O'Neill, Luke A J; Cooper, Matthew A; Horvat, Jay C; Hansbro, Philip M

2017-08-01

Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1β responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma. To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1β in severe, steroid-resistant asthma. We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1β responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1β responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1β antibody. Roles for IL-1β-induced neutrophilic inflammation were examined using IL-1β and anti-Ly6G. Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1β responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1β expression. Treatment with anti-IL-1β, Ac-YVAD-cho, and MCC950 suppressed IL-1β responses and the important steroid-resistant features of disease in mice, whereas IL-1β administration recapitulated these features. Neutrophil depletion suppressed IL-1β-induced steroid-resistant airway hyperresponsiveness. NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.

Targeting Phosphoinositide 3-Kinase γ in Airway Smooth Muscle Cells to Suppress Interleukin-13-Induced Mouse Airway Hyperresponsiveness

PubMed Central

Jiang, Haihong; Xie, Yan; Abel, Peter W.; Toews, Myron L.; Townley, Robert G.; Casale, Thomas B.

2012-01-01

We recently reported that phosphoinositide 3-kinase γ (PI3Kγ) directly regulates airway smooth muscle (ASM) contraction by modulating Ca2+ oscillations. Because ASM contraction plays a critical role in airway hyperresponsiveness (AHR) of asthma, the aim of the present study was to determine whether targeting PI3Kγ in ASM cells could suppress AHR in vitro and in vivo. Intranasal administration into mice of interleukin-13 (IL-13; 10 μg per mouse), a key pathophysiologic cytokine in asthma, induced AHR after 48 h, as assessed by invasive tracheostomy. Intranasal administration of a broad-spectrum PI3K inhibitor or a PI3Kγ-specific inhibitor 1 h before AHR assessment attenuated IL-13 effects. Airway responsiveness to bronchoconstrictor agonists was also examined in precision-cut mouse lung slices pretreated without or with IL-13 for 24 h. Acetylcholine and serotonin dose-response curves indicated that IL-13-treated lung slices had a 40 to 50% larger maximal airway constriction compared with controls. Furthermore, acetylcholine induced a larger initial Ca2+ transient and increased Ca2+ oscillations in IL-13-treated primary mouse ASM cells compared with control cells, correlating with increased cell contraction. As expected, PI3Kγ inhibitor treatment attenuated IL-13-augmented airway contractility of lung slices and ASM cell contraction. In both control and IL-13-treated ASM cells, small interfering RNA-mediated knockdown of PI3Kγ by 70% only reduced the initial Ca2+ transient by 20 to 30% but markedly attenuated Ca2+ oscillations and contractility of ASM cells by 50 to 60%. This report is the first to demonstrate that PI3Kγ in ASM cells is important for IL-13-induced AHR and that acute treatment with a PI3Kγ inhibitor can ameliorate AHR in a murine model of asthma. PMID:22543031

Apigenin inhibits TGF-β1-induced proliferation and migration of airway smooth muscle cells.

PubMed

Li, Li-Hua; Lu, Bin; Wu, Hong-Ke; Zhang, Hao; Yao, Fei-Fei

2015-01-01

It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-β1 (TGF-β1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-β1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-β1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-β1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.

Pidotimod exacerbates allergic pulmonary infection in an OVA mouse model of asthma.

PubMed

Fu, Luo-Qin; Li, Ya-Li; Fu, Ai-Kun; Wu, Yan-Ping; Wang, Yuan-Yuan; Hu, Sheng-Lan; Li, Wei-Fen

2017-10-01

Pidotimod is a synthetic dipeptide with biological and immuno‑modulatory properties. It has been widely used for treatment and prevention of recurrent respiratory infections. However, its impact on the regulation of allergic pulmonary inflammation is still not clear. In the current study, an ovalbumin (OVA)‑induced allergic asthma model was used to investigate the immune‑modulating effects of pidotimod on airway eosinophilia, mucus metaplasia and inflammatory factor expression compared with dexamethasone (positive control). The authors determined that treatment with pidotimod exacerbated pulmonary inflammation as demonstrated by significantly increased eosinophil infiltration, dramatically elevated immunoglobulin E production, and enhanced T helper 2 response. Moreover, treatment failed to attenuate mucus production in lung tissue, and did not reduce OVA‑induced high levels of FIZZ1 and Arg1 expression in asthmatic mice. In contrast, administration of dexamethasone was efficient in alleviating allergic airway inflammation in OVA‑induced asthmatic mice. These data indicated that pidotimod as an immunotherapeutic agent should be used cautiously and the effectiveness for controlling allergic asthma needs further evaluation and research.

Exposure to Triclosan Augments the Allergic Response to Ovalbumin in a Mouse Model of Asthma

PubMed Central

Anderson, Stacey E.; Franko, Jennifer; Kashon, Michael L.; Anderson, Katie L.; Hubbs, Ann F.; Lukomska, Ewa; Meade, B. Jean

2015-01-01

During the last decade, there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouthwashes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75 to 3% (0.375–1.5 mg/mouse/day) for 28 consecutive days. Concordantly, mice were ip injected with OVA (0.9 μg) and aluminum hydroxide (0.5 mg) on days 1 and 10 and challenged with OVA (125 μg) by pharyngeal aspiration on days 19 and 27. Compared with the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, interleukin-13 cytokine levels, and numbers of lung eosinophils were demonstrated when mice were coexposed to OVA and triclosan. Statistically significant increases in OVA-specific and nonspecific airway hyperreactivity were observed for all triclosan coexposed groups compared with the vehicle and OVA controls. In these studies, exposure to triclosan alone was not demonstrated to be allergenic; however, coexposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens. PMID:23192912

Mangiferin attenuates TH1/TH2 cytokine imbalance in an ovalbumin-induced asthmatic mouse model.

PubMed

Guo, Hong-Wei; Yun, Chen-Xia; Hou, Guang-Han; Du, Jun; Huang, Xin; Lu, Yi; Keller, Evan T; Zhang, Jian; Deng, Jia-Gang

2014-01-01

Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway.

Mangiferin Attenuates Th1/Th2 Cytokine Imbalance in an Ovalbumin-Induced Asthmatic Mouse Model

PubMed Central

Hou, Guang-Han; Du, Jun; Huang, Xin; Lu, Yi; Keller, Evan T.; Zhang, Jian; Deng, Jia-Gang

2014-01-01

Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway. PMID:24955743

Low Doses of Exogenous Interferon-γ Attenuated Airway Inflammation Through Enhancing Fas/FasL-Induced CD4+ T Cell Apoptosis in a Mouse Asthma Model

PubMed Central

Yao, Yinan; Lu, Shan; Lu, Guohua

2012-01-01

To investigate whether low doses of exogenous interferon (IFN)-γ attenuate airway inflammation, and the underlying mechanisms, in asthma. C57BL/6 mice (n=42), after intraperitoneal ovalbumin (OVA) sensitization on day 0 and day 12, were challenged with OVA aerosol for 6 consecutive days. Different doses of IFN-γ were then administered intraperitoneally 5 min before each inhalation during OVA challenge. Airway hyperresponsiveness, airway inflammatory cells, cytokine profiles, and Fas/FasL expression on CD4+ T cells were evaluated in an asthma model. The effect of various IFN-γ doses on Fas/FasL expression and CD4+ T cell apoptosis were assessed in vitro. We demonstrated that low doses of IFN-γ reduced pulmonary infiltration of inflammatory cells, Th2 cytokine production, and goblet cells hyperplasia (P<0.05), while high doses of endogenous IFN-γ had almost no effect. We also found that low doses of IFN-γ relocated Fas/FasL to the CD4+ T cell surface in the asthma model (P<0.05) and increased FasL-induced apoptosis in vitro (P<0.05). Furthermore, treatment with MFL-3, an anti-FasL antibody, partially abolished the anti- inflammatory properties of IFN-γ in the airway rather than affecting the Th1/Th2 balance. This research has revealed an alternative mechanism in asthma that involves low doses of IFN-γ, which attenuate airway inflammation through enhancing Fas/FasL-induced CD4+ T cell apoptosis. PMID:22994871

Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri

Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise actionmore » of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.« less

Silibinin attenuates allergic airway inflammation in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu

Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesismore » of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.« less

Inhibitory effect of kefiran on ovalbumin-induced lung inflammation in a murine model of asthma.

PubMed

Kwon, Ok-Kyoung; Ahn, Kyung-Seop; Lee, Mee-Young; Kim, So-Young; Park, Bo-Young; Kim, Mi-Kyoung; Lee, In-Young; Oh, Sei-Ryang; Lee, Hyeong-Kyu

2008-12-01

Kefiran is a major component of kefir which is a microbial symbiont mixture that produces jelly-like grains. This study aimed to evaluate the therapeutic availability of kefiran on the ovalbumin-induced asthma mouse model in which airway inflammation and airway hyper-responsiveness were found in the lung. BALB/c mice sensitized and challenged to ovalbumin were treated intra-gastrically with kefiran 1 hour before the ovalbumin challenge. Kefiran significantly suppressed ovalbumin-induced airway hyper-responsiveness (AHR) to inhaled methacholine. Administration of kefiran significantly inhibited the release of both eosinophils and other inflammatory cells into bronchoalveolar lavage (BAL) fluid and lung tissue which was measured by Diff-Quik. Interleukin-4 (IL-4) and interleukin-5 (IL-5) were also reduced to normal levels after administration of kefiran in BAL fluid. Histological studies demonstrate that kefiran substantially inhibited ovalbumin-induced eosinophilia in lung tissue by H&E staining and goblet cell hyperplasia in the airway by PAS staining. Taken above data, kefiran may be useful for the treatment of inflammation of lung tissue and airway hyper-responsiveness in a murine model and may have therapeutic potential for the treatment of allergic bronchial asthma.

18β-Glycyrrhetinic acid, the major bioactive component of Glycyrrhizae Radix, attenuates airway inflammation by modulating Th2 cytokines, GATA-3, STAT6, and Foxp3 transcription factors in an asthmatic mouse model.

PubMed

Kim, Seung-Hyung; Hong, Jung-Hee; Lee, Ji-Eun; Lee, Young-Cheol

2017-06-01

18β-Glycyrrhetinic acid (18Gly), the major bioactive component of Glycyrrhizae Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological properties. Although 18Gly is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic inflammatory lung disease have not been examined. Moreover, there are no in vivo studies on the anti-asthmatic effects of 18Gly in allergic asthma. We investigated its effect and mechanism of action in airway inflammation in a BALB/c mouse model of allergic asthma. Interestingly, 18Gly strongly suppressed airway hyperresponsiveness, accumulation of inflammatory cells, and levels of T helper type 2 (Th2) cytokines (interleukin (IL)-5 and IL-13) in bronchoalveolar lavage fluid (BALF). It also attenuated lung IL-5, IL-13, and IL-4 expression, but it upregulated peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression in lungs. Moreover, it exerted immunomodulatory effects by suppressing Th2 cytokines (IL-5, IL-13) production through upregulation of forkhead box p3 (Foxp3), and downregulation of signal transducer and activator of transcription (STAT6), GATA-binding protein 3 (GATA-3), and retinoic acid-related orphan receptor γ t (RORγt) expression. These results suggest that the anti-asthmatic activity of 18Gly may occur by the suppression of IL-5, IL-13, and OVA-specific Immunoglobulin E (IgE) production through inhibition of the RORγt, STAT6, GATA-3 pathways and upregulation of the Foxp3 transcription pathway. Also, 18Gly treatment was protective against the oxidative stress by inducing significant decrease of reactive oxygen species (ROS) generation in MH-S alveolar macrophage cells. Our results suggest that 18Gly can improve allergic asthma and can be a novel therapeutic component for the treatment of allergic asthma. Copyright © 2017 Elsevier B.V. All rights reserved.

Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribeiro-Filho, Jaime; Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba; Calheiros, Andrea Surrage

Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effectsmore » of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine mechanisms involve inhibition of Ca{sup 2+} influx, and IL-13 and eotaxin secretion. • No significant toxicity was observed in mice orally treated with curine for 7 days. • Curine has the potential for the development of anti-asthmatic drugs.« less

Mast cell-dependent IL-33/ST2 signaling is protective against the development of airway hyperresponsiveness in a house dust mite mouse model of asthma.

PubMed

Zoltowska Nilsson, A M; Lei, Y; Adner, M; Nilsson, G P

2018-03-01

Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated with the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM)-induced asthma. Mast cell-deficient C57BL/6-Kit W-sh (Wsh) mice engrafted with either wild-type (Wsh + MC-WT) or ST2-deficient bone marrow-derived mast cells (Wsh + MC-ST2KO) were exposed to HDM delivered intranasally. An exacerbated development of AHR in response to HDM was seen in Wsh + MC-ST2KO compared with Wsh + MC-WT mice. The contribution of this IL-33/ST2-dependent mast cell response to AHR seems to reside within the smaller airways in the peripheral parts of the lung, as suggested by the isolated yet marked effect on tissue resistance. Considering the absence of a parallel increase in cellular inflammation in bronchoalveolar lavage fluid (BALF) and lung, the aggravated AHR in Wsh + MC-ST2KO mice seems to be independent of cellular inflammation. We observed an association between the elevated AHR and reduced PGE 2 levels in BALF . Due to the protective properties of PGE 2 in airway responses, it is conceivable that IL-33/ST2-dependent mast cell induction of PGE 2 could be responsible for the dampening effect on AHR. In conclusion, we reveal that IL-33/ST2-dependent mast cell responses can have a protective, rather than causative role, in the development of AHR.

Key Role of Group V Secreted Phospholipase A2 in Th2 Cytokine and Dendritic Cell-Driven Airway Hyperresponsiveness and Remodeling

PubMed Central

Henderson Jr, William R.; Ye, Xin; Lai, Ying; Ni, Zhanglin; Bollinger, James G.; Tien, Ying-Tzang; Chi, Emil Y.; Gelb, Michael H.

2013-01-01

Background Previous work has shown that disruption of the gene for group X secreted phospholipase A2 (sPLA2-X) markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA2s in the mammalian genome, the involvement of other sPLA2s in the asthma model is possible – in particular, the group V sPLA2 (sPLA2-V) that like sPLA2-X is highly active at hydrolyzing membranes of mammalian cells. Methodology and Principal Findings The allergen-driven asthma phenotype was significantly reduced in sPLA2-V-deficient mice but to a lesser extent than observed previously in sPLA2-X-deficient mice. The most striking difference observed between the sPLA2-V and sPLA2-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA) in the sPLA2-V−/− mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V−/− mice diminishes Th2 cytokine responses in the airways. Conclusions This paper illustrates the diverse roles of sPLA2s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA2-V as a potential new therapy to treat asthma and other allergic disorders. PMID:23451035

THE EFFECTS OF ANTI-INFLAMMATORY IFNγ AND PRO-INFLAMMATORY TNFα, IL-1β ON CHEMOKINE RELEASE IN MOUSE EPITHELIAL CELLS

EPA Science Inventory

RATIONALE: Asthma is a chronic inflammatory disorder of the airways that affects nearly 20 million individuals in the US. Airway inflammation is a hallmark characteristic of asthma and is the result of numerous pro-inflammatory cytokines such as IL-1β and TNFα . Interestingly...

Asthma in inner city children: recent insights: United States.

PubMed

Dutmer, Cullen M; Kim, Haejin; Searing, Daniel A; Zoratti, Edward M; Liu, Andrew H

2018-04-01

Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016-2017) advances in the understanding of asthma in US inner city children. Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children.

Mouse Model of Halogenated Platinum Salt Hypersensitivity ...

EPA Pesticide Factsheets

Occupational exposure to halogenated platinum salts can trigger the development of asthma. Concern for increased asthma risk exists for the general population due to the use of platinum (Pt) in catalytic converters and its emerging use as a diesel fuel additive. To investigate airway responses to Pt, we developed a mouse model of Pt hypersensitivity. Previously, we confirmed the dermal sensitizing potency of ammonium hexachloroplatinate (AHCP) using an ex vivo [3H]methyl thymidine labeling version of the local lymph node assay in BALB/c mice. Here, we investigated the ability of AHCP to induce airway responses in mice sensitized by the dermal route. Mice were sensitized through application of 100 µL 1% AHCP in DMSO to the shaved back on days 0, 5 and 19, and 25 µl to each ear on days 10, 11 and 12. Unsensitized mice received vehicle. On day 24, mice were challenged by oropharyngeal aspiration (OPA) with 0 or 100 µg AHCP in saline. Before and immediately after challenge, airway responses were assessed using whole body plethysmography (WBP). On day 26, changes in ventilatory responses to methacholine (Mch) aerosol were assessed by WBP; dose-dependent increases in Mch responsiveness occurred in sensitized mice. Bronchoalveolar lavage fluid harvested from sensitized mice contained an average of 7.5% eosinophils compared to less than 0.5% in control mice (p < 0.05). This model will be useful for assessing both relative sensitizing potency and cross-reacti

Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback

PubMed Central

Moon, Hyung-Geun; Kang, Chil Sung; Choi, Jun-Pyo; Choi, Dong Sic; Choi, Hyun Il; Choi, Yong Wook; Jeon, Seong Gyu; Yoo, Joo-Yeon; Jang, Myoung Ho; Gho, Yong Song; Kim, Yoon-Keun

2013-01-01

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback. PMID:23306703

Effect of choline chloride in allergen-induced mouse model of airway inflammation.

PubMed

Mehta, A K; Gaur, S N; Arora, N; Singh, B P

2007-10-01

The incidence of asthma has increased the world over, and current therapies for the disease suffer from potential side-effects. This has created an opportunity to develop novel therapeutic approaches. Here, the anti-inflammatory activity of choline was investigated in a mouse model of allergic airway inflammation. Choline (1 mg.kg(-1)) was administered via oral gavage or intranasally before and after ovalbumin (OVA) challenge in sensitised mice. Airway hyperresponsiveness (AHR) to methacholine was measured in the mice by whole-body plethysmography. Type-2 T-helper cell cytokine and leukotriene levels were estimated in bronchoalveolar lavage fluid (BALF) and spleen culture supernatant by ELISA. Eosinophil peroxidase activity was also determined in the BALF supernatant. Choline treatment in sensitised mice before OVA challenge via oral/intranasal routes significantly inhibited eosinophilic airway inflammation and eosinophil peroxidase activity. It also reduced immunoglobulin E and G1 production and inhibited the release of type-2 T-helper cell cytokines and leukotrienes. However, the development of AHR was prevented effectively by intranasal choline treatment. Most importantly, choline treatment after OVA challenge by both routes could reverse established asthmatic conditions in mice by inhibiting AHR, eosinophilic airway inflammation and other inflammatory parameters. This study provides a new therapeutic approach for controlling as well as preventing asthma exacerbations.

Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite-induced asthma mouse model.

PubMed

Ishii, T; Niikura, Y; Kurata, K; Muroi, M; Tanamoto, K; Nagase, T; Sakaguchi, M; Yamashita, N

2018-03-01

House dust mites (HDMs) are a common source of allergens that trigger both allergen-specific and innate immune responses in humans. Here, we examined the effect of allergen concentration and the involvement of Toll-like receptor 4 (TLR4) in the process of sensitization to house dust mite allergens in an HDM extract-induced asthma mouse model.　Intranasal administration of HDM extract induced an immunoglobulin E response and eosinophilic inflammation in a dose-dependent manner from 2.5 to 30 μg/dose. In TLR4-knockout mice, the infiltration of eosinophils and neutrophils into the lung was decreased compared with that in wild-type mice in the early phase of inflammation (total of three doses). However, in the late phase of inflammation (total of seven doses), eosinophil infiltration was significantly greater in TLR4-knockout mice than in wild-type mice. This suggests that the roles of TLR4 signaling are different between the early phase and the later phase of HDM allergen-induced inflammation. Thus, innate immune response through TLR4 regulated the response to HDM allergens, and the regulation was altered during the phase of inflammation. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Mina: A Th2 response regulator meets TGFβ

PubMed Central

Pillai, Meenu R.; Lian, Shangli; Bix, Mark

2014-01-01

The JmjC protein Mina is an important immune response regulator. Classical forward genetics first discovered its immune role in 2009 in connection with the development of T helper 2 (Th2) cells. This prompted investigation into Mina’s role in the two best-studied contexts where Th2 responses are essential: atopic asthma and helminth expulsion. In work focused on a mouse model of atopic asthma, Mina deficiency was found to ameliorate airway hyper-resistance and pulmonary inflammation. And, in a case-control study genetic variation at the human MINA locus was found to be associated with the development of childhood atopic asthma. Although the underlying cellular and molecular mechanism of Mina’s involvement in pulmonary inflammation remains unknown, our recent work on parasitic helminth expulsion suggests the possibility that, rather than T cells, epithelial cells responding to TGFβ may play the dominant role. Here we review the growing body of literature on the emerging Mina pathway in T cells and epithelial cells and attempt to set these into a broader context. PMID:25282476

Repeated irradiations with gamma-rays at a Dose of 0.5 Gy may exacerbate asthma.

PubMed

Fang, Su-ping; Tago, Fumitoshi; Tanaka, Takashi; Simura, Noriko; Muto, Yasuko; Goto, Resuke; Kojima, Shuji

2005-06-01

We previously showed that 0.5 Gy whole-body gamma-ray irradiation with a single or small number of repeated exposures inhibits tumor growth in mice, via elevation of the IFN-gamma/IL-4 ratio concomitantly with a decrease in the percentage of B cells. Here we examined whether repeated 0.5 Gy gamma-rays irradiation can improve asthma in an OVA-induced asthmatic mouse model. We found that repeated irradiation (10 times) with 0.5 Gy of gamma-rays significantly increased total IgE in comparison with the disease-control group. The levels of IL-4 and IL-5 were also significantly higher in the gamma-ray-irradiated group, while that of IFN-gamma was significantly lower, resulting in a further decrease of the IFN-gamma/IL-4 ratio from the normal value. These results indicate that the repeated irradiation with gamma-rays may exacerbate asthma, and may have opposite effects on different immune reactions unlike the irradiation with a single or small number of repeated exposures.

Gene Silencing of SOCS3 by siRNA Intranasal Delivery Inhibits Asthma Phenotype in Mice

PubMed Central

Mazzeo, Carla; Gámez, Cristina; Rodriguez Marco, Ainara; de Zulueta, Ana; Sanz, Veronica; Bilbao, Izaskun; Ruiz-Cabello, Jesús; Zubeldia, Jose M.; del Pozo, Victoria

2014-01-01

Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma. PMID:24637581

Naringin Protects Ovalbumin-Induced Airway Inflammation in a Mouse Model of Asthma.

PubMed

Guihua, Xiong; Shuyin, Liu; Jinliang, Gao; Wang, Shumin

2016-04-01

Many plant species containing flavonoids have been widely used in traditional Chinese medicine. Naringin, a well-known flavanone glycoside of citrus fruits, possesses antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, anti-osteoporosis, and anti-carcinogenic properties. The aim of the study was to investigate the anti-asthmatic effects of naringin and the possible mechanisms. Asthma model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, and dexamethasone (2 mg/kg, orally) and naringin (5 mg/kg, 10 mg/kg, orally). Airway resistance (Raw) were measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, OVA-specific serum and BALF IgE levels and Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th1/Th2 cells was evaluated by flow cytometry (FCM). T-bet and GABA3 in the lung were evaluated by Western blot. Our study demonstrated that naringin inhibited OVA-induced increases in Raw and eosinophil count; OVA-induced effects on interleukin (IL)-4 and INF-gamma levels were blunted with naringin administration. Histological studies demonstrated that naringin substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. Flow cytometry studies demonstrated that naringin substantially inhibited Th2 cells and enhanced Th1 cells. Naringin substantially inhibited GABA3 and increased T-bet. These findings suggest that naringin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Transcription factor RBP-J-mediated signalling regulates basophil immunoregulatory function in mouse asthma model.

PubMed

Qu, Shuo-Yao; He, Ya-Long; Zhang, Jian; Wu, Chang-Gui

2017-09-01

Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma. Bone marrow BA were prepared by bone marrow cell culture in the presence of recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of the CD49b + microbeads. The recombination signal binding protein J (RBP-J -/- ) BA were co-cultured with T cells, and the supernatant and the T-cell subtypes were examined. The results indicated disruption of the capacity of BA for antigen presentation alongside an up-regulation of the immunoregulatory function. This was possibly due to the low expression of OX40L in the RBP-J -/- BA. Basophils were adoptively transferred to ovalbumin-sensitized recipient mice, to establish an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid, airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were determined. Overall, our results indicate that the RBP-J-mediated Notch signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J influences the immunoregulatory functions of BA, which include activation of T cells and their differentiation into T helper cell subtypes. The Notch signalling pathway is a potential therapeutic target for BA-based immunotherapy against asthma. © 2017 John Wiley & Sons Ltd.

Persistent activation of an innate immune axis translates respiratory viral infection into chronic lung disease

PubMed Central

Kim, Edy Y.; Battaile, John T.; Patel, Anand C.; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H.; Benoit, Loralyn A.; Byers, Derek E.; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W.; Morton, Jeffrey D.; Castro, Mario; Polineni, Deepika; Patterson, G. Alexander; Schwendener, Reto A.; Allard, John D.; Peltz, Gary; Holtzman, Michael J.

2008-01-01

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of a chronic lung disease that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after infection with a common type of respiratory virus is cleared to trace levels of noninfectious virus. Unexpectedly, the chronic inflammatory disease arises independently of an adaptive immune response and is driven by IL-13 produced by macrophages stimulated by CD1d-dependent TCR-invariant NKT cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a novel NKT cell-macrophage innate immune axis. PMID:18488036

Effect of inhaled and systemic glucocorticoid treatment on CD4+ regulatory and effector T cells in a mouse model of allergic asthma.

PubMed

Zuśka-Prot, Monika; Maślanka, Tomasz

2017-04-01

To achieve a better understanding of mechanisms underlying the anti-asthmatic action of inhaled and systemic glucocorticoids (GCs) and to provide more data regarding the risk of a negative effect of inhaled GCs on CD4 + T cells, a study was conducted on the effect of ciclesonide and methylprednisolone on CD4 + effector (Teff), regulatory (Treg) and resting (Trest) T cells within respiratory and extra-respiratory tissues in a mouse model of allergic asthma. The study indicated that one, and possibly a key mechanism, underlying the anti-asthmatic action of inhaled and systemic GCs is the prevention of the activation and clonal expansion of CD4 + Teff cells in the mediastinal lymph nodes (MLNs), which consequently prevents infiltration of the lungs with CD4 + Teff cells. The beneficial effects of GCs in asthma treatment were not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of Treg cells. The results demonstrated that inhaled and systemic GCs induced comparable depletion of normal CD4 + Teff, Trest and Treg cells in the MLNs, head and neck lymph nodes and peripheral blood. Furthermore, inhaled, but not systemic GC therapy, led to the loss of these cells in the lungs. Thus, the study suggests that inhaled GC therapy may not be safer at all than systemic one with respect to the adverse effect on CD4 + T cells present within and outside the respiratory tract. Moreover, administration of inhaled GCs can produce negative effects on lung-residing CD4 + T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Components of Streptococcus pneumoniae suppress allergic airways disease and NKT cells by inducing regulatory T cells.

PubMed

Thorburn, Alison N; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M

2012-05-01

Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.

Functional Effects of TGF-beta1 on Mesenchymal Stem Cell Mobilization in Cockroach Allergen Induced Asthma

PubMed Central

Xian, Lingling; Li, Changjun; Xu, Ting; Plunkett, Beverly; Huang, Shau-Ku; Wan, Mei; Cao, Xu

2014-01-01

Mesenchymal stem cells (MSCs) have been suggested to participate in immune regulation and airway repair/remodeling. Transforming growth factor β1 (TGFβ1) is critical in the recruitment of stem/progenitor cells for tissue repair, remodeling and cell differentiation. In this study, we sought to investigate the role of TGFβ1 in MSC migration in allergic asthma. We examined nestin expression (a marker for MSCs) and TGFβ1 signaling activation in airways in cockroach allergen (CRE) induced mouse models. Compared with control mice, there were increased nestin+ cells in airways, and higher levels of active TGFβ1 in serum and p-Smad2/3 expression in lungs of CRE-treated mice. Increased activation of TGFβ1 signaling was also found in CRE-treated MSCs. We then assessed MSC migration induced by conditioned medium (ECM) from CRE-challenged human epithelium in air/liquid interface (ALI) culture in Transwell assays. MSC migration was stimulated by ECM, but was significantly inhibited by either TGFβ1 neutralizing antibody or TβR1 inhibitor. Intriguingly, increased migration of MSCs from blood and bone marrow to the airway was also observed after systemic injection of GFP+-MSCs, and from bone marrow of Nes-GFP mice following CRE challenge. Furthermore, TGFβ1 neutralizing antibody inhibited the CRE-induced MSC recruitment, but promoted airway inflammation. Finally, we investigated the role of MSCs in modulating CRE induced T cell response, and found that MSCs significantly inhibited CRE-induced inflammatory cytokine secretion (IL-4, IL13, IL17 and IFN-γ) by CD4+ T cells. These results suggest that TGFβ1 may be a key pro-migratory factor in recruiting MSCs to the airways in mouse models of asthma. PMID:24711618

Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection.

PubMed

Fujimoto, Yousuke; Hasegawa, Shunji; Matsushige, Takeshi; Wakiguchi, Hiroyuki; Nakamura, Tamaki; Hasegawa, Hideki; Nakajima, Noriko; Ainai, Akira; Oga, Atsunori; Itoh, Hiroshi; Shirabe, Komei; Toda, Shoichi; Atsuta, Ryo; Morishima, Tsuneo; Ohga, Shouichi

2017-08-22

Asthmatic patients present more rapid progression of respiratory distress after A(H1N1)pdm09 influenza infection than after seasonal infection. Here, we sought to clarify the pathophysiology of early deterioration in asthmatic patients after A(H1N1)pdm09 infection. Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. In asthma/A(H1N1)pdm09 mice, IL-6 and TNF-α levels peaked at 3 days post-infection and were higher than those in all other groups. IFN-γ levels in asthma/A(H1N1)pdm09 mice at 3 days post-infection were higher than in all other mice at any time point, whereas at 7 days post-infection, the levels were lowest in asthma/A(H1N1)pdm09 mice. Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group. Histopathological examination showed more inflammatory cell infiltration and lung tissue destruction in the asthma/A(H1N1)pdm09 group than in any other group. The distinct cytokine profiles in A(H1N1)pdm09-infected asthmatic mice indicated excessive inflammation and virus replication within a few days after infection. Thus, bronchial asthma could be a more exacerbating factor for pandemic influenza infection than for seasonal influenza infection.

Peri-adolescent asthma symptoms cause adult anxiety-related behavior and neurobiological processes in mice

PubMed Central

Caulfield, Jasmine I.; Caruso, Michael J.; Michael, Kerry C.; Bourne, Rebecca A.; Chirichella, Nicole R.; Klein, Laura C.; Craig, Timothy; Bonneau, Robert H.; August, Avery; Cavigelli, Sonia A.

2017-01-01

Human and animal studies have shown that physical challenges and stressors during adolescence can have significant influences on behavioral and neurobiological development associated with internalizing disorders such as anxiety and depression. Given the prevalence of asthma during adolescence and increased rates of internalizing disorders in humans with asthma, we used a mouse model to test if and which symptoms of adolescent allergic asthma (airway inflammation or labored breathing) cause adult anxiety- and depression-related behavior and brain function. To mimic symptoms of allergic asthma in young BALB/cJ mice (postnatal days [P] 7–57; N=98), we induced lung inflammation with repeated intranasal administration of house dust mite extract (most common aeroallergen for humans) and bronchoconstriction with aerosolized methacholine (non-selective muscarinic receptor agonist). Three experimental groups, in addition to a control group, included: (1) “Airway inflammation only”, allergen exposure 3 times/week, (2) “Labored breathing only”, methacholine exposure once/week, and (3) “Airway inflammation + Labored breathing”, allergen and methacholine exposure. Compared to controls, mice that experienced methacholine-induced labored breathing during adolescence displayed a ~20% decrease in time on open arms of the elevated plus maze in early adulthood (P60), a ~30% decrease in brainstem serotonin transporter (SERT) mRNA expression and a ~50% increase in hippocampal serotonin receptor 1a (5Htr1a) and corticotropin releasing hormone receptor 1 (Crhr1) expression in adulthood (P75). This is the first evidence that experimentally-induced clinical symptoms of adolescent asthma alter adult anxiety-related behavior and brain function several weeks after completion of asthma manipulations. PMID:28284954

Staphylococcal enterotoxin A-activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation.

PubMed

Zeng, Wei-Ping; McFarland, Margaret M; Zhou, Baohua; Holtfreter, Silva; Flesher, Susan; Cheung, Ambrose; Mallick, Avishek

2017-02-01

T H 2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins. We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote T H 2 differentiation of allergen-specific CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspecific regulatory T (Treg) cells to create a T H 2-polarizing cytokine milieu. Ovalbumin (OVA)-specific, staphylococcal enterotoxin A (SEA)-nonreactive naive CD4 Tcon cells were cocultured with SEA-reactive allergen-nonspecific Treg or CD4 Tcon cells in the presence of OVA and SEA. The OVA-specific CD4 T cells were then analyzed for IL-13 and IFN-γ expression. SEA-activated Treg cells were analyzed for the expression of the T H 2-polarizing cytokine IL-4 and the T-cell activation markers CD69 and CD62L. For asthma induction, mice were intratracheally sensitized with OVA or cat dander extract (CDE) alone or together with SEA and then challenged with OVA or CDE. Mice were also subject to transient Treg cell depletion before sensitization with OVA plus SEA. Asthma features and T H 2 differentiation in these mice were analyzed. SEA-activated Treg cells induced IL-13 but suppressed IFN-γ expression in OVA-specific CD4 Tcon cells. SEA-activated Treg cells expressed IL-4, upregulated CD69, and downregulated CD62L. Sensitization with OVA plus SEA but not OVA alone induced asthma, and SEA exacerbated asthma induced by CDE. Depletion of Treg cells abolished these effects of SEA and IL-13 expression in OVA-specific T cells. SEA promoted T H 2 responses of allergen-specific T cells and asthma pathogenesis by activating Treg cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor

PubMed Central

Wang, Xiaoqin; Xu, Weidong; Mohapatra, Subhra; Kong, Xiaoyuan; Li, Xu; Lockey, Richard F; Mohapatra, Shyam S

2008-01-01

Background Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally. Methods Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines. Results SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls. Conclusion These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma. PMID:18279512

Effect of Kuwanon G isolated from the root bark of Morus alba on ovalbumin-induced allergic response in a mouse model of asthma.

PubMed

Jung, Hyo Won; Kang, Seok Yong; Kang, Jong Seong; Kim, A Ryun; Woo, Eun-Rhan; Park, Yong-Ki

2014-11-01

The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)-induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA-specific IgE and Th2 cytokines (IL-4, IL-5, and IL-13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA-specific IgE and IL-4, IL-5, and IL-13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd.

Bakery flour dust exposure causes non-allergic inflammation and enhances allergic airway inflammation in mice

PubMed Central

Marraccini, Paolo; Brass, David M.; Hollingsworth, John W.; Maruoka, Shuichiro; Garantziotis, Stavros; Schwartz, David A.

2014-01-01

Background Baker’s asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker’s asthma, yet the etiology and pathogenesis of baker’s asthma remain poorly understood. Objective We sought to develop a mouse model of baker’s asthma that could be used to characterize the development and progression of baker’s asthma. Methods We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of OVA sensitization and challenge. Results Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a tlr4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA sensitized and challenged mice. Conclusions Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation. PMID:18564331

School exposure and asthma.

PubMed

Esty, Brittany; Phipatanakul, Wanda

2018-05-01

To provide a comprehensive overview of common school exposures and the association between school exposures and pediatric asthma morbidity. A comprehensive literature review was performed using PubMed. Full-length, peer-reviewed studies published in English were considered for review. In vivo, in vitro, and animal studies were excluded. Studies of school exposure to cockroach, mouse, dust mite, dog, cat, molds, pollution, and endotoxin associated with asthma and asthma morbidity were considered. The current literature establishes an association between school exposure and pediatric asthma morbidity. There is a need for ongoing research to evaluate the effects of school-based environmental interventions on asthma morbidity. It is evident that the indoor school environment is a significant reservoir of allergens, molds, pollutants, and endotoxin and that there is an association between school exposure and pediatric asthma morbidity. School-based interventions have the potential for substantial individual, community, and public health benefit. It is important that researchers continue to study the health effects associated with school exposures and assess cost-effectiveness of multifaceted school-based interventions. Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Experimental asthma persists in IL-33 receptor knockout mice because of the emergence of thymic stromal lymphopoietin-driven IL-9+ and IL-13+ type 2 innate lymphoid cell subpopulations.

PubMed

Verma, Mukesh; Liu, Sucai; Michalec, Lidia; Sripada, Anand; Gorska, Magdalena M; Alam, Rafeul

2017-11-10

IL-33 plays an important role in the development of experimental asthma. We sought to study the role of the IL-33 receptor suppressor of tumorigenicity 2 (ST2) in the persistence of asthma in a mouse model. We studied allergen-induced experimental asthma in ST2 knockout (KO) and wild-type control mice. We measured airway hyperresponsiveness by using flexiVent; inflammatory indices by using ELISA, histology, and real-time PCR; and type 2 innate lymphoid cells (ILC2s) in lung single-cell preparations by using flow cytometry. Airway hyperresponsiveness was increased in allergen-treated ST2 KO mice and comparable with that in allergen-treated wild-type control mice. Peribronchial and perivascular inflammation and mucus production were largely similar in both groups. Persistence of experimental asthma in ST2 KO mice was associated with an increase in levels of thymic stromal lymphopoietin (TSLP), IL-9, and IL-13, but not IL-5, in bronchoalveolar lavage fluid. Expectedly, ST2 deletion caused a reduction in IL-13 + CD4 T cells, forkhead box P3-positive regulatory T cells, and IL-5 + ILC2s. Unexpectedly, ST2 deletion led to an overall increase in innate lymphoid cells (CD45 + lin - CD25 + cells) and IL-13 + ILC2s, emergence of a TSLP receptor-positive IL-9 + ILC2 population, and an increase in intraepithelial mast cell numbers in the lung. An anti-TSLP antibody abrogated airway hyperresponsiveness, inflammation, and mucus production in allergen-treated ST2 KO mice. It also caused a reduction in innate lymphoid cell, ILC2, and IL-9 + and IL-13 + ILC2 numbers in the lung. Genetic deletion of the IL-33 receptor paradoxically increases TSLP production, which stimulates the emergence of IL-9 + and IL-13 + ILC2s and mast cells and leads to development of chronic experimental asthma. An anti-TSLP antibody abrogates all pathologic features of asthma in this model. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model.

PubMed

Wu, Hui-Mei; Fang, Lei; Shen, Qi-Ying; Liu, Rong-Yu

2015-10-01

c-Jun N-terminal kinase (JNK) relays extracellular stimuli through phosphorylation cascades that lead to various cell responses. In the present study, we aimed to investigate the effect of the JNK inhibitor SP600125 on the resolution of airway inflammation, and the underlying mechanism using a murine acute asthma model. Female C57BL/6 mice were sensitized with saline or ovalbumin (OVA) on day 0, and challenged with OVA on day 14-20. Meanwhile, some of the mice were treated with SP600125 (30 mg/kg) intraperitoneally 2 h before each challenge. The airway inflammation was evaluated by counting the numbers of various types of inflammatory cells in bronchoalveolar lavage fluid (BALF), histopathology, cytokines production and mucus secretion in individual mouse. In addition, we analyzed the protein levels of phosphorylated JNK and TLR9 in the lung tissues. SP600125 markedly reduced the invasion of inflammatory cells into the peribronchial regions, and decreased the numbers of eosinophils, monocytes, neutrophils and lymphocytes in BALF. SP600125 also reduced the level of plasma OVA-specific IgE, lowered the production of pro-inflammatory cytokines in BALF and alleviated mucus secretion. Meanwhile, SP600125 inhibited OVA-induced, increased expression of p-JNK and TLR9 in the lung tissues. Collectively, our data demonstrated that SP600125 promoted resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model. The JNK-TLR9 pathway may be a new therapeutic target in the treatment for the allergic asthma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Peri-adolescent asthma symptoms cause adult anxiety-related behavior and neurobiological processes in mice.

PubMed

Caulfield, Jasmine I; Caruso, Michael J; Michael, Kerry C; Bourne, Rebecca A; Chirichella, Nicole R; Klein, Laura C; Craig, Timothy; Bonneau, Robert H; August, Avery; Cavigelli, Sonia A

2017-05-30

Human and animal studies have shown that physical challenges and stressors during adolescence can have significant influences on behavioral and neurobiological development associated with internalizing disorders such as anxiety and depression. Given the prevalence of asthma during adolescence and increased rates of internalizing disorders in humans with asthma, we used a mouse model to test if and which symptoms of adolescent allergic asthma (airway inflammation or labored breathing) cause adult anxiety- and depression-related behavior and brain function. To mimic symptoms of allergic asthma in young BALB/cJ mice (postnatal days [P] 7-57; N=98), we induced lung inflammation with repeated intranasal administration of house dust mite extract (most common aeroallergen for humans) and bronchoconstriction with aerosolized methacholine (non-selective muscarinic receptor agonist). Three experimental groups, in addition to a control group, included: (1) "Airway inflammation only", allergen exposure 3 times/week, (2) "Labored breathing only", methacholine exposure once/week, and (3) "Airway inflammation+Labored breathing", allergen and methacholine exposure. Compared to controls, mice that experienced methacholine-induced labored breathing during adolescence displayed a ∼20% decrease in time on open arms of the elevated plus maze in early adulthood (P60), a ∼30% decrease in brainstem serotonin transporter (SERT) mRNA expression and a ∼50% increase in hippocampal serotonin receptor 1a (5Htr1a) and corticotropin releasing hormone receptor 1 (Crhr1) expression in adulthood (P75). This is the first evidence that experimentally-induced clinical symptoms of adolescent asthma alter adult anxiety-related behavior and brain function several weeks after completion of asthma manipulations. Copyright © 2017 Elsevier B.V. All rights reserved.

The Protective Effects of Astaxanthin on the OVA-Induced Asthma Mice Model.

PubMed

Hwang, Yun-Ho; Hong, Seong-Gyeol; Mun, Seul-Ki; Kim, Su-Jin; Lee, Sung-Ju; Kim, Jong-Jin; Kang, Kyung-Yun; Yee, Sung-Tae

2017-11-21

Although astaxanthin has a variety of biological activities such as anti-oxidant effects, inhibitory effects on skin deterioration and anti-inflammatory effects, its effect on asthma has not been studied. In this paper, the inhibitory effect of astaxanthin on airway inflammation in a mouse model of ovalbumin (OVA)-induced asthma was investigated. We evaluated the number of total cells, Th1/2 mediated inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness as well as histological structure. The level of total IgE, IgG1, IgG2a, OVA-specific IgG1, and OVA-specific IgG2a were also examined. The oral administration of 50 mg/mL astaxanthin inhibited the respiratory system resistance, elastance, newtonian resistance, tissue damping, and tissue elastance. Also, astaxanthin suppressed the total cell number, IL-4, and IL-5, and increased the IFN-γ in the BALF. In the sera, total IgE, IgG1, and OVA-specific IgG1 were reduced by astaxanthin exposure and IgG2a and OVA-specific IgG2a were enhanced via oral administration of astaxanthin. Infiltration of inflammatory cells in the lung, production of mucus, lung fibrosis, and expression of caspase-1 or caspase-3 were suppressed in OVA-induced asthmatic animal treated with astaxanthin. These results suggest that astaxanthin may have therapeutic potential for treating asthma via inhibiting Th2-mediated cytokine and enhancing Th1-mediated cytokine.

Novel Small Airway Bronchodilator Responses to Rosiglitazone in Mouse Lung Slices

PubMed Central

Bai, Yan; Donovan, Chantal; Esposito, James G.; Tan, Xiahui; Sanderson, Michael J.

2014-01-01

There is a need to identify novel agents that elicit small airway relaxation when β2-adrenoceptor agonists become ineffective in difficult-to-treat asthma. Because chronic treatment with the synthetic peroxisome proliferator activated receptor (PPAR)γ agonist rosiglitazone (RGZ) inhibits airway hyperresponsiveness in mouse models of allergic airways disease, we tested the hypothesis that RGZ causes acute airway relaxation by measuring changes in small airway size in mouse lung slices. Whereas the β-adrenoceptor agonists albuterol (ALB) and isoproterenol induced partial airway relaxation, RGZ reversed submaximal and maximal contraction to methacholine (MCh) and was similarly effective after precontraction with serotonin or endothelin-1. Concentration-dependent relaxation to RGZ was not altered by the β-adrenoceptor antagonist propranolol and was enhanced by ALB. RGZ-induced relaxation was mimicked by other synthetic PPARγ agonists but not by the putative endogenous agonist 15-deoxy-PGJ2 and was not prevented by the PPARγ antagonist GW9662. To induce airway relaxation, RGZ inhibited the amplitude and frequency of MCh-induced Ca2+ oscillations of airway smooth muscle cells (ASMCs). In addition, RGZ reduced MCh-induced Ca2+ sensitivity of the ASMCs. Collectively, these findings demonstrate that acute bronchodilator responses induced by RGZ are PPARγ independent, additive with ALB, and occur by the inhibition of ASMC Ca2+ signaling and Ca2+ sensitivity. Because RGZ continues to elicit relaxation when β-adrenoceptor agonists have a limited effect, RGZ or related compounds may have potential as bronchodilators for the treatment of difficult asthma. PMID:24188042

Exposure to Particulate Hexavalent Chromium Exacerbates Allergic Asthma Pathology

PubMed Central

Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

2011-01-01

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. PMID:22178736

Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics.

PubMed

Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

2015-01-01

Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body's response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction.

Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics

PubMed Central

Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

2015-01-01

Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body’s response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction. PMID:25922579

Mina: a Th2 response regulator meets TGFβ.

PubMed

Pillai, Meenu R; Lian, Shangli; Bix, Mark

2014-12-01

The JmjC protein Mina is an important immune response regulator. Classical forward genetics first discovered its immune role in 2009 in connection with the development of T helper 2 (Th2) cells. This prompted investigation into Mina's role in the two best-studied contexts where Th2 responses are essential: atopic asthma and helminth expulsion. In work focused on a mouse model of atopic asthma, Mina deficiency was found to ameliorate airway hyper-resistance and pulmonary inflammation. And, in a case-control study genetic variation at the human MINA locus was found to be associated with the development of childhood atopic asthma. Although the underlying cellular and molecular mechanism of Mina's involvement in pulmonary inflammation remains unknown, our recent work on parasitic helminth expulsion suggests the possibility that, rather than T cells, epithelial cells responding to TGFβ may play the dominant role. Here we review the growing body of literature on the emerging Mina pathway in T cells and epithelial cells and attempt to set these into a broader context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Accumulation of BDCA1⁺ dendritic cells in interstitial fibrotic lung diseases and Th2-high asthma.

PubMed

Greer, Alexandra M; Matthay, Michael A; Kukreja, Jasleen; Bhakta, Nirav R; Nguyen, Christine P; Wolters, Paul J; Woodruff, Prescott G; Fahy, John V; Shin, Jeoung-Sook

2014-01-01

Dendritic cells (DCs) significantly contribute to the pathology of several mouse lung disease models. However, little is known of the contribution of DCs to human lung diseases. In this study, we examined infiltration with BDCA1⁺ DCs of human lungs in patients with interstitial lung diseases or asthma. Using flow cytometry, we found that these DCs increased by 5∼6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using FcεRI and MHCII as the specific markers for BDCA1⁺ DCs, we found that the numbers of BDCA1⁺ DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1⁺ DCs in human lung diseases associated with interstitial fibrosis or Th2 airway inflammation.

Bitter taste receptors in the wrong place: novel airway smooth muscle targets for treating asthma.

PubMed

Liggett, Stephen B

2014-01-01

There is a need to expand the classes of drugs used to treat obstructive lung diseases to achieve better outcomes. With only one class of direct bronchodilators (β-agonists), we sought to find receptors on human airway smooth muscle (ASM) that act via a unique mechanism to relax the muscle, have a diverse agonist binding profile to enhance the probability of finding new therapeutics, and relax ASM with equal or greater efficacy than β-agonists. We have found that human and mouse ASM express six bitter taste receptor (TAS2R) subtypes, previously thought only to exist in taste buds of the tongue. Agonists acting at TAS2Rs evoke profound bronchodilation via a Ca(2+)-dependent mechanism. TAS2R function is not altered in asthma models, undergoes minimal tachyphylaxis upon repetitive dosing, and relaxes even under extreme desensitization of relaxation by β-agonists. Taken together, TAS2Rs on ASM represent a novel pathway to consider for development of agonists in the treatment of asthma and chronic obstructive lung disease.

Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.

PubMed

Hogan, Mary Beth; Piktel, Debra; Hubbs, Ann F; McPherson, Leslie E; Landreth, Kenneth S

2008-12-01

Patient factors that cause long-term airway remodeling are largely unidentified. This suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. To investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. The C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.

Correlation of PD-1/PD-L1 Signaling Pathway with Treg/Th17 Imbalance from Asthmatic Children.

PubMed

Xi, Xia; Liu, Jing-Mei; Guo, Jun-Ying

2018-06-06

The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in asthma pathogenesis, but no therapeutic targets could modulate the Th17/Treg balance specifically for asthma. Since previous studies have shown the programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis in this disease, we hypothesized that the PD-1/PD-L1 pathway might be involved in the regulation of Treg/Th17 imbalance in asthmatic children. The percentage of Treg and Th17 cells and the expression of PD-1 and PD-L1 were detected by flow cytometry in children with asthma and healthy controls. CD4+ T cells were stimulated with Th17 and Treg differentiating factors, and treated with anti-PD-1. Then cells were harvested and measured for Th17 and Treg percentages and Foxp3 and RORγt levels using RT-PCR. We observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 in the two subsets also changed in the mild persistent and moderate to severe persistent groups compared with healthy controls. In vitro, administration of anti-PD-1 could decrease Th17 percentages and RORγt mRNA, and increase Treg percentages and Foxp3 mRNA in CD4+ T cells of children with asthma in the mild persistent and moderate to persistent groups. Additionally, the role played by anti-PD-1 in regulating Treg/Th17 balance was further confirmed in an asthmatic mouse model. Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. Treatment with anti-PD-1 posed protective effects on asthma models, providing a novel theoretical target for asthma. © 2018 S. Karger AG, Basel.

Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in a House Dust Mite Model of Asthma

PubMed Central

Lei, Ying; Adner, Mikael; Hellman, Lars; Nilsson, Gunnar

2015-01-01

In several clinical and experimental studies IL-33 and its receptor have been found to play important roles in the development of asthma and allergic airway inflammation. We evaluated the effects of vaccination against IL-33 in a mouse model of airway inflammation induced by house dust mite (HDM) allergen. Balb/c mice received the IL-33 vaccine subcutaneously, followed by intranasal administration of HDM for up to six weeks. Vaccination against IL-33 induced high titers of specific anti-IL-33 IgG antibodies that inhibited HDM-induced airway hyperresponsiveness (AHR) in the conducting airways and tissue damping. The vaccination also attenuated the HDM-induced elevation in the numbers of eosinophils in bronchoalveolar lavage fluid (BALF) and suppressed the accumulation of inflammatory cells in the airways. Furthermore, the levels of IL-17A, IL-25, IL-33 and TSLP in lung tissue homogenates were reduced by vaccination against IL-33. These observations demonstrate that vaccination against IL-33 inhibits HDM-induced development of AHR, airway inflammation and production of inflammatory cytokines. The results also indicate an important role of IL-33 in the regulation of AHR of the distal lung compartments. Thus, administration of such a vaccine is potentially an effective therapeutic tool for treating allergic asthma. PMID:26214807

Aqueous Extract of Gumiganghwal-tang, a Traditional Herbal Medicine, Reduces Pulmonary Fibrosis by Transforming Growth Factor-β1/Smad Signaling Pathway in Murine Model of Chronic Asthma.

PubMed

Jeon, Woo-Young; Shin, In-Sik; Shin, Hyeun-Kyoo; Jin, Seong Eun; Lee, Mee-Young

2016-01-01

Gumiganghwal-tang is a traditional herbal prescription that is used widely for the treatment of the common cold and inflammatory diseases in Korea and other Asian countries. In this study, we investigated the protective effects of a Gumiganghwal-tang aqueous extract (GGTA) against airway inflammation and pulmonary fibrosis using a mouse model of chronic asthma. Chronic asthma was modeled in BALB/c mice via sensitization/challenge with an intraperitoneal injection of 1% ovalbumin (OVA) and inhalation of nebulized 1% OVA for 4 weeks. GGTA (100 mg/kg or 200 mg/kg) was also administered by oral gavage once a day for 4 weeks. We investigated the number of inflammatory cells, production of T-helper type 2 (Th2) cytokines, chemokine and the total transforming growth factor-β1 (TGF-β1) in bronchoalveolar lavage fluid (BALF); the levels of immunoglobulin E (IgE) in the plasma; the infiltration of inflammatory cells in lung tissue; and the expression of TGF-β1, Smad-3, and collagen in lung tissue. Our results revealed that GGTA lowered the recruitment of inflammatory cells (particularly, lymphocyte); and decreased the production of Th2 cytokines, chemokine and total TGF-β1; and attenuated the levels of total and OVA-specific IgE; and decreased the infiltration of inflammatory cells. Moreover, GGTA significantly reduced the expression of TGF-β1 and Smad-3, and lowered collagen deposition. These results indicate that GGTA reduces airway inflammation and pulmonary fibrosis by regulating Th2 cytokines production and the TGF-β1/Smad-3 pathway, thus providing a potential treatment for chronic asthma.

Interleukin-13-induced MUC5AC expression is regulated by a PI3K–NFAT3 pathway in mouse tracheal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Fugui; Li, Wen; Zhou, Hongbin

Highlights: • IL-13 specifically induced NFAT3 activation in mouse tracheal epithelial cells. • CsA and LY294002 significantly blocked IL-13-induced MUC5AC production. • The PI3K–NFAT3 pathway is positively involved in IL-13-induced MUC5AC production. - Abstract: Interleukin-13 (IL-13) plays a critical role in asthma mucus overproduction, while the mechanisms underlying this process are not fully elucidated. Previous studies showed that nuclear factor of activated T cells (NFAT) is involved in the pathogenesis of asthma, but whether it can directly regulate IL-13-induced mucus (particularly MUC5AC) production is still not clear. Here we showed that IL-13 specifically induced NFAT3 activation through promoting its dephosphorylationmore » in air–liquid interface (ALI) cultures of mouse tracheal epithelial cells (mTECs). Furthermore, both Cyclosporin A (CsA, a specific NFAT inhibitor) and LY294002 (a Phosphoinositide 3-kinase (PI3K) inhibitor) significantly blocked IL-13-induced MUC5AC mRNA and protein production through the inhibition of NFAT3 activity. We also confirmed that CsA could not influence the forkhead Box A2 (Foxa2) and mouse calcium dependent chloride channel 3 (mClca3) expression in IL-13-induced MUC5AC production, which both are known to be important in IL-13-stimulated mucus expression. Our study is the first to demonstrate that the PI3K–NFAT3 pathway is positively involved in IL-13-induced mucus production, and provided novel insights into the molecular mechanism of asthma mucus hypersecretion.« less

Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCG.

PubMed

Ou-Yang, Hai-Feng; Hu, Xing-Bin; Ti, Xin-Yu; Shi, Jie-Ran; Li, Shu-Jun; Qi, Hao-Wen; Wu, Chang-Gui

2009-09-01

Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette-Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4(+) CD25(+) Foxp3(+) T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4(+) CD25(+) T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-beta (TGF-beta)-producing CD4(+) CD25(+) Foxp3(+) regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma.

Effect of cat and daycare exposures on the risk of asthma in children with atopic dermatitis.

PubMed

Gaffin, Jonathan M; Spergel, Jonathan M; Boguniewicz, Mark; Eichenfield, Lawrence F; Paller, Amy S; Fowler, Joseph F; Dinulos, James G; Tilles, Stephen A; Schneider, Lynda C; Phipatanakul, Wanda

2012-01-01

Atopic dermatitis (AD) in young children is often followed by the development of asthma (atopic march). The role of environmental exposures is unclear in this high-risk population. We aimed to determine the predictive relationship between indoor allergen exposures, particularly pets, rodents, and cockroaches, to the development of asthma in a prospective pediatric cohort. Children with AD and a family history of allergy were followed prospectively with questionnaire ascertainment of environmental exposure to cats, dogs, cockroaches, rats, and mice. Asthma was diagnosed by study physicians based on caregiver reports of symptoms continually assessed over the course of the study period. Fifty-five of the 299 children developed asthma by the end of the study. Cat exposure had a strong and independent effect to reduce the risk of developing asthma across all analyses (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.53). Dog, mouse, rat, and cockroach exposures did not significantly influence the development of asthma. Daycare exposure had the largest risk reduction for the development of asthma (OR, 0.08; 95% CI, 0.03-0.19). Maternal asthma (OR, 2.93; 95% CI, 1.29-6.67), baseline body mass index (OR, 1.23; 95% CI, 1.08-1.42), and specific immunoglobulin E to house-dust mix at 3 years were each independent risk factors for the development of asthma. In children with AD, cat and daycare exposure may reduce the risk of developing early childhood asthma.

Rhinovirus infection of allergen-sensitized and -challenged mice induces eotaxin release from functionally polarized macrophages.

PubMed

Nagarkar, Deepti R; Bowman, Emily R; Schneider, Dina; Wang, Qiong; Shim, Jee; Zhao, Ying; Linn, Marisa J; McHenry, Christina L; Gosangi, Babina; Bentley, J Kelley; Tsai, Wan C; Sajjan, Umadevi S; Lukacs, Nicholas W; Hershenson, Marc B

2010-08-15

Human rhinovirus is responsible for the majority of virus-induced asthma exacerbations. To determine the immunologic mechanisms underlying rhinovirus (RV)-induced asthma exacerbations, we combined mouse models of allergic airways disease and human rhinovirus infection. We inoculated OVA-sensitized and challenged BALB/c mice with rhinovirus serotype 1B, a minor group strain capable of infecting mouse cells. Compared with sham-infected, OVA-treated mice, virus-infected mice showed increased lung infiltration with neutrophils, eosinophils and macrophages, airway cholinergic hyperresponsiveness, and increased lung expression of cytokines including eotaxin-1/CCL11, IL-4, IL-13, and IFN-gamma. Administration of anti-eotaxin-1 attenuated rhinovirus-induced airway eosinophilia and responsiveness. Immunohistochemical analysis showed eotaxin-1 in the lung macrophages of virus-infected, OVA-treated mice, and confocal fluorescence microscopy revealed colocalization of rhinovirus, eotaxin-1, and IL-4 in CD68-positive cells. RV inoculation of lung macrophages from OVA-treated, but not PBS-treated, mice induced expression of eotaxin-1, IL-4, and IL-13 ex vivo. Macrophages from OVA-treated mice showed increased expression of arginase-1, Ym-1, Mgl-2, and IL-10, indicating a shift in macrophage activation status. Depletion of macrophages from OVA-sensitized and -challenged mice reduced eosinophilic inflammation and airways responsiveness following RV infection. We conclude that augmented airway eosinophilic inflammation and hyperresponsiveness in RV-infected mice with allergic airways disease is directed in part by eotaxin-1. Airway macrophages from mice with allergic airways disease demonstrate a change in activation state characterized in part by altered eotaxin and IL-4 production in response to RV infection. These data provide a new paradigm to explain RV-induced asthma exacerbations.

Expression, purification and characterization of Der f 27, a new allergen from dermatophagoides farinae

PubMed Central

Lin, Jianli; Li, Meng; Liu, Yulin; Jiang, Congli; Wu, Yulan; Wang, Yuanyuan; Gao, Anjian; Liu, Zhigang; Yang, Pingchang; Liu, Xiaoyu

2015-01-01

The house dust mite (HDM), Dermatophagoidesfarinae (D. farina), is one of the most important indoor allergen sources and a major elicitor of allergic asthma; itscharacterization is important in the diagnosis and immunotherapy of mite allergen-relevant diseases. This study aims to characterize a novel allergen, the D. farinae-derived serpin (Der f 27). In this study, the total RNA of D. farinae was extracted, and the Der f 27 gene was cloned and expressed. The allergenicity of recombinant Der f 27 protein was determined by enzyme-linked immunosorbent assay, and Western-blotting with the sera of asthma patients, and skin prick test (SPT) in allergic human subjects. A r-Der f 27 allergic asthma mouse model was established. The cloned Der f 27 gene has been presented at the Gene Bank with an accession number of KM009995. The IgE levels of r-Der f 27 in the serum from r-Der f 27 SPT positive allergic patients were 3 folds more than healthy subjects. The Der f 27 SPT positive ratewas 42.1% in 19 DM-SPT positive patients. Airway hyperresponsiveness, serum specific IgE, and levels of interleukin-4 in the spleen cell culture supernatant were significantly increased in allergic asthma mice sensitized to r-Der f 27. In conclusion, Der f 27 is a new subtype of house mite allergen. PMID:26328010

Macrophages induce an allergen-specific and long-term suppression in a mouse asthma model.

PubMed

Vissers, J L M; van Esch, B C A M; Hofman, G A; van Oosterhout, A J M

2005-12-01

Increasing evidence suggests that macrophages (Mphi) play a crucial downregulatory role in the initiation and progression of allergic asthma. Recently, the current authors demonstrated that ovalbumin (OVA)-loaded Mphi (OVA-Mphi) suppress subsequent OVA-induced airway manifestations of asthma and that this effect could be potentiated upon selective activation. In the present study, the authors further delineated the underlying pathway by which Mphi exert this immunosuppressive effect. To examine the migration of OVA-Mphi, cells were labelled with 5'chloromethylfluorescein diacetate (CMFDA) and were administered (i.v.) into OVA-sensitised BALB/c mice. After 20 h, the relevant organs were dissected and analysed using fluorescent microscopy. Allergen-specificity was investigated by treating OVA-sensitised mice with keyhole limpet haemocyanin (KLH)-Mphi activated with immunostimulatory sequence oligodeoxynucleotide (ISS-ODN). By lengthening the period between treatment and challenge to 4 weeks it was examined whether OVA-Mphi exerted an immunosuppressive memory response. Strikingly, CMFDA-labelled Mphi were not trapped in the lungs, but migrated to the spleen. ISS-ODN-stimulated KLH-Mphi failed to suppress OVA-induced airway manifestations of asthma. Moreover, treatment with ISS-ODN-stimulated OVA-Mphi was still effective after lengthening the period between treatment and challenge. These data demonstrate that allergen-loaded macrophages can induce an indirect immunosuppressive response that is allergen-specific and long lasting, which are both hallmarks of a memory lymphocyte response.

IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

PubMed

Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

2015-01-01

Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

Novel Insights in Mammalian Catalase Heme Maturation: Effect of NO and Thioredoxin-1

PubMed Central

Chakravarti, Ritu; Gupta, Karishma; Majors, Alana; Ruple, Lisa; Aronica, Mark; Stuehr, Dennis J.

2016-01-01

Catalase is a tetrameric heme-containing enzyme with essential antioxidant functions in biology. Multiple factors including nitric oxide (NO) have been shown to attenuate its activity. However, the possible impact of NO in relation to the maturation of active catalase, including its heme acquisition and tetramer formation, has not been investigated. We found that NO attenuates heme insertion into catalase in both short-term and long-term incubations. The NO inhibition in catalase heme incorporation was associated with defective oligomerization of catalase, such that inactive catalase monomers and dimers accumulated in place of the mature tetrameric enzyme. We also found that GAPDH plays a key role in mediating these NO effects on the structure and activity of catalase. Moreover, the NO sensitivity of catalase maturation could be altered up or down by manipulating the cellular expression level or activity of thioredoxin-1, a known protein-SNO denitrosylase enzyme. In a mouse model of allergic inflammatory asthma, we found that lungs from allergen-challenged mice contained a greater percentage of dimeric catalase relative to tetrameric catalase in the unchallenged control, suggesting that the mechanisms described here are in play in the allergic asthma model. Together, our study shows how maturation of active catalase can be influenced by NO, S-nitrosylated GAPDH, and thioredoxin-1, and how maturation may become compromised in inflammatory conditions such as asthma. PMID:25659933

Novel insights in mammalian catalase heme maturation: effect of NO and thioredoxin-1.

PubMed

Chakravarti, Ritu; Gupta, Karishma; Majors, Alana; Ruple, Lisa; Aronica, Mark; Stuehr, Dennis J

2015-05-01

Catalase is a tetrameric heme-containing enzyme with essential antioxidant functions in biology. Multiple factors including nitric oxide (NO) have been shown to attenuate its activity. However, the possible impact of NO in relation to the maturation of active catalase, including its heme acquisition and tetramer formation, has not been investigated. We found that NO attenuates heme insertion into catalase in both short-term and long-term incubations. The NO inhibition in catalase heme incorporation was associated with defective oligomerization of catalase, such that inactive catalase monomers and dimers accumulated in place of the mature tetrameric enzyme. We also found that GAPDH plays a key role in mediating these NO effects on the structure and activity of catalase. Moreover, the NO sensitivity of catalase maturation could be altered up or down by manipulating the cellular expression level or activity of thioredoxin-1, a known protein-SNO denitrosylase enzyme. In a mouse model of allergic inflammatory asthma, we found that lungs from allergen-challenged mice contained a greater percentage of dimeric catalase relative to tetrameric catalase in the unchallenged control, suggesting that the mechanisms described here are in play in the allergic asthma model. Together, our study shows how maturation of active catalase can be influenced by NO, S-nitrosylated GAPDH, and thioredoxin-1, and how maturation may become compromised in inflammatory conditions such as asthma. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of cat and daycare exposures on the risk of asthma in children with atopic dermatitis

PubMed Central

Gaffin, Jonathan M.; Spergel, Jonathan M.; Boguniewicz, Mark; Eichenfield, Lawrence F.; Paller, Amy S.; Fowler, Joseph F.; Dinulos, James G.; Tilles, Stephen A.; Schneider, Lynda C.

2012-01-01

Atopic dermatitis (AD) in young children is often followed by the development of asthma (atopic march). The role of environmental exposures is unclear in this high-risk population. We aimed to determine the predictive relationship between indoor allergen exposures, particularly pets, rodents, and cockroaches, to the development of asthma in a prospective pediatric cohort. Children with AD and a family history of allergy were followed prospectively with questionnaire ascertainment of environmental exposure to cats, dogs, cockroaches, rats, and mice. Asthma was diagnosed by study physicians based on caregiver reports of symptoms continually assessed over the course of the study period. Fifty-five of the 299 children developed asthma by the end of the study. Cat exposure had a strong and independent effect to reduce the risk of developing asthma across all analyses (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05–0.53). Dog, mouse, rat, and cockroach exposures did not significantly influence the development of asthma. Daycare exposure had the largest risk reduction for the development of asthma (OR, 0.08; 95% CI, 0.03–0.19). Maternal asthma (OR, 2.93; 95% CI, 1.29–6.67), baseline body mass index (OR, 1.23; 95% CI, 1.08–1.42), and specific immunoglobulin E to house-dust mix at 3 years were each independent risk factors for the development of asthma. In children with AD, cat and daycare exposure may reduce the risk of developing early childhood asthma. PMID:22584195

Exacerbating effects of PM2.5 in OVA-sensitized and challenged mice and the expression of TRPA1 and TRPV1 proteins in lungs.

PubMed

Liu, Hong; Fan, Xinsheng; Wang, Naiqian; Zhang, Yuyan; Yu, Jinghua

2017-10-01

To investigate the effects of particulate matter ≤ 2.5 microns (PM2.5) on asthma-related phenotypes and on lung expression of TRPA1 and TRPV1 proteins in a mouse model of asthma. Female BALB/c mice were utilized to establish 28- and 42-day asthma models. Mice were sensitized with ovalbumin (OVA) and challenged with OVA, OVA plus normal saline (NS), or OVA plus PM2.5 at two doses, 1.6 or 8.0 mg kg -1 . PM2.5 was instilled intratracheally without anesthesia. After the final OVA challenge was performed, 24 hours later, the changes in airway resistance (RI) and lung dynamic compliance (Cdyn) in response to acetylcholine chloride (ACH) were evaluated, and blood, bronchoalveolar lavage fluid (BALF) and lung tissue were taken at that time. The number of eosinophils in blood and various leukocytes in BALF were determined. Lung protein was extracted and probed for TRPA1 and TRPV1 expression. Interleukin (IL)-13, substance P (SP), prostaglandin D 2 (PGD 2 ) and nerve growth factor (NGF) in BALF were measured by enzyme-linked immunosorbent assay. PM2.5 treated mice showed significantly greater changes in the number of inflammatory cells in blood and BALF, in RI and Cdyn in response to ACH, and in lung histopathology, indicated by inflammatory cell infiltration, thickened bronchial smooth muscles and bronchial mucosa damage, compared to controls. In addition, higher expression of TRPA1 and TRPV1 in lung and IL-13, SP, PGD 2 and NGF in BALF were seen in mice exposed to PM2.5. All effects were most pronounced in mice in the 42-day model. PM2.5 exacerbates effects of asthma in this model, possibly by regulating TRPA1 and TRPV1 and the relevant neurokines.

Defective natural killer cell activity in a mouse model of eczema herpeticum.

PubMed

Kawakami, Yuko; Ando, Tomoaki; Lee, Jong-Rok; Kim, Gisen; Kawakami, Yu; Nakasaki, Tae; Nakasaki, Manando; Matsumoto, Kenji; Choi, Youn Soo; Kawakami, Toshiaki

2017-03-01

Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH. We sought to establish and characterize a mouse model of EH. We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer. Inoculation of HSV1 induced severe erosive skin lesions in eczematous mice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematous mice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematous mice. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Perillyl alcohol suppresses antigen-induced immune responses in the lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes,more » its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.« less

Nociceptin/orphanin FQ (N/OFQ) modulates immunopathology and airway hyperresponsiveness representing a novel target for the treatment of asthma.

PubMed

Singh, Shailendra R; Sullo, Nikol; Matteis, Maria; Spaziano, Giuseppe; McDonald, John; Saunders, Ruth; Woodman, Lucy; Urbanek, Konrad; De Angelis, Antonella; De Palma, Raffaele; Berair, Rachid; Pancholi, Mitesh; Mistry, Vijay; Rossi, Francesco; Guerrini, Remo; Calò, Girolamo; D'Agostino, Bruno; Brightling, Christopher E; Lambert, David G

2016-04-01

There is evidence supporting a role for the nociceptin/orphanin FQ (N/OFQ; NOP) receptor and its endogenous ligand N/OFQ in the modulation of neurogenic inflammation, airway tone and calibre. We hypothesized that NOP receptor activation has beneficial effects upon asthma immunopathology and airway hyperresponsiveness. Therefore, the expression and function of N/OFQ and the NOP receptor were examined in healthy and asthmatic human airway tissues. The concept was further addressed in an animal model of allergic asthma. NOP receptor expression was investigated by quantitative real-time PCR. Sputum N/OFQ was determined by RIA. N/OFQ function was tested using several assays including proliferation, migration, collagen gel contraction and wound healing. The effects of N/OFQ administration in vivo were studied in ovalbumin (OVA)-sensitized and challenged mice. NOP receptors were expressed on a wide range of human and mouse immune and airway cells. Eosinophils expressed N/OFQ-precursor mRNA and their number correlated with N/OFQ concentration. N/OFQ was found in human sputum and increased in asthma. Additionally, in asthmatic human lungs N/OFQ immunoreactivity was elevated. NOP receptor activation inhibited migration of immunocytes and increased wound healing in airway structural cells. Furthermore, N/OFQ relaxed spasmogen-stimulated gel contraction. Remarkably, these findings were mirrored in OVA-mice where N/OFQ treatment before or during sensitization substantially reduced airway constriction and immunocyte trafficking to the lung, in particular eosinophils. N/OFQ also reduced inflammatory mediators and mucin production. We demonstrated a novel dual airway immunomodulator/bronchodilator role for N/OFQ and suggest targeting this system as an innovative treatment for asthma. © 2016 The British Pharmacological Society.

Mouse allergen, lung function, and atopy in Puerto Rican children.

PubMed

Forno, Erick; Cloutier, Michelle M; Datta, Soma; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy B; Brehm, John; Hamilton, Robert G; Alvarez, María; Colón-Semidey, Angel; Acosta-Pérez, Edna; Canino, Glorisa; Celedón, Juan C

2012-01-01

To examine the relation between mouse allergen exposure and asthma in Puerto Rican children. Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV(1) and FEV(1)/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures. Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV(1) in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6-132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI =  -0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV(1) (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01). Mouse allergen is associated with a higher FEV(1) and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures.

Mouse Allergen, Lung Function, and Atopy in Puerto Rican Children

PubMed Central

Forno, Erick; Cloutier, Michelle M.; Datta, Soma; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy B.; Brehm, John; Hamilton, Robert G.; Alvarez, María; Colón-Semidey, Angel; Acosta-Pérez, Edna; Canino, Glorisa; Celedón, Juan C.

2012-01-01

Objective To examine the relation between mouse allergen exposure and asthma in Puerto Rican children. Methods Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV1 and FEV1/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures. Results Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV1 in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6–132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI =  −0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5–0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV1 (+28.3 ml, 95% CI = 1.4–55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6–0.9, P<0.01). Conclusions Mouse allergen is associated with a higher FEV1 and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures. PMID:22815744

Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse

PubMed Central

Roviezzo, Fiorentina; Rossi, Antonietta; Caiazzo, Elisabetta; Orlando, Pierangelo; Riemma, Maria A.; Iacono, Valentina M.; Guarino, Andrea; Ialenti, Armando; Cicala, Carla; Peritore, Alessio; Capasso, Raffaele; Di Marzo, Vincenzo; Izzo, Angelo A.

2017-01-01

One important risk factor for the development of asthma is allergen sensitization. Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to – and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization, by using ovalbumin (OVA) as sensitizing agent in the mouse. PEA levels were dramatically reduced in the bronchi of OVA-treated animals. This effect was coupled to a significant up-regulation of CB2 and GPR55 receptors, two of the proposed molecular PEA targets, in bronchi harvested from allergen-sensitized mice. PEA supplementation (10 mg/kg, 15 min before each allergen exposure) prevented OVA-induced bronchial hyperreactivity, but it did not affect IgE plasma increase. On the other hand, PEA abrogated allergen-induced cell recruitment as well as pulmonary inflammation. Evaluation of pulmonary sections evidenced a significant inhibitory action of PEA on pulmonary mast cell recruitment and degranulation, an effect coupled to a reduction of leukotriene C4 production. These findings demonstrate that allergen sensitization negatively affects PEA bronchial levels and suggest that its supplementation has the potential to prevent the development of asthma-like features. PMID:29311913

Antiasthmatic Effects of Herbal Complex MA and Its Fermented Product MA128.

PubMed

Kim, Dong-Seon; Kim, Seung-Hyung; Kim, Bok-Kyu; Yang, Min Cheol; Ma, Jin Yeul

2012-01-01

This study was conducted to determine if oral administration of the novel herbal medicine, MA, and its Lactobacillus acidophilus fermented product, MA128, have therapeutic properties for the treatment of asthma. Asthma was induced in BALB/c mice by systemic sensitization to ovalbumin (OVA) followed by intratracheal, intraperitoneal, and aerosol allergen challenges. MA and MA128 were orally administered 6 times a week for 4 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was assessed and samples of bronchoalveolar lavage fluid, lung cells, and serum were collected for further analysis. We investigated the effect of MA and MA128 on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, OVA-specific IgE production, and Th1/Th2 cytokine production in this mouse model of asthma. In BALB/c mice, we found that MA and MA128 treatment suppressed eosinophil infiltration into airways and blood, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13, IL-17, Eotaxin, and OVA-specific IgE, by upregulating the production of OVA-specific Th1 cytokine (IFN-γ), and by downregulating OVA-specific Th2 cytokine (IL-4) in the culture supernatant of spleen cells. The effectiveness of MA was increased by fermentation with Lactobacillus acidophilus.

Mast Cells Can Amplify Airway Reactivity and Features of Chronic Inflammation in an Asthma Model in Mice

PubMed Central

Williams, Cara M.M.; Galli, Stephen J.

2000-01-01

The importance of mast cells in the development of the allergen-induced airway hyperreactivity and inflammation associated with asthma remains controversial. We found that genetically mast cell–deficient WBB6F1-W/Wv mice that were sensitized to ovalbumin (OVA) without adjuvant, then challenged repetitively with antigen intranasally, exhibited much weaker responses in terms of bronchial hyperreactivity to aerosolized methacholine, lung tissue eosinophil infiltration, and numbers of proliferating cells within the airway epithelium than did identically treated WBB6F1-+/+ normal mice. However, W/Wv mice that had undergone selective reconstitution of tissue mast cells with in vitro–derived mast cells of congenic +/+ mouse origin exhibited airway responses that were very similar to those of the +/+ mice. By contrast, W/Wv mice that were sensitized with OVA emulsified in alum and challenged with aerosolized OVA exhibited levels of airway hyperreactivity and lung tissue eosinophil infiltration that were similar to those of the corresponding +/+ mice. Nevertheless, these W/Wv mice exhibited significantly fewer proliferating cells within the airway epithelium than did identically treated +/+ mice. These results show that, depending on the “asthma model” investigated, mast cells can either have a critical role in, or not be essential for, multiple features of allergic airway responses in mice. PMID:10934234

Advancing a multilevel framework for epidemiologic research on asthma disparities.

PubMed

Wright, Rosalind J; Subramanian, S V

2007-11-01

Our understanding of asthma epidemiology is growing increasingly complex. Asthma outcomes are clearly socially patterned, with asthma ranking as a leading cause of health disparities among minority and low socioeconomic groups. Yet, the increasing prevalence and marked disparities in asthma remain largely unexplained by known risk factors. In the United States, asthma disproportionately affects nonwhite children living in urban areas and children living in poverty. Low socioeconomic status (SES), ethnic minority group status, and residence in an inner-city environment are closely intertwined in the United States, making it a challenge to fully disentangle the independent effects of each of these characteristics on asthma morbidity. In addition, studies show geographic variation in asthma outcomes across large cities and neighborhoods within cities that cannot be explained by economic factors alone. Although more limited data are available, studies in rural areas also suggest the stratification of risk based on SES and the proportion of minorities. Among low-SES areas, those with predominantly minority, segregated populations seem especially burdened. Marginalized populations of lower socioeconomic position are disproportionately exposed to irritants (eg, tobacco smoke), pollutants (eg, diesel-related particles), and indoor allergens (eg, cockroach and mouse allergen). Moreover, these marginalized individuals may also live in communities that are increasingly socially toxic, which, in turn, may be related to the increased experience of psychosocial stress that may influence asthma morbidity. Epidemiologic trends suggest that asthma may provide an excellent paradigm for understanding the role of community-level contextual factors in disease. Specifically, a multilevel approach that includes an ecological perspective may help to explain heterogeneities in asthma expression across socioeconomic and geographic boundaries that, to date, remain largely unexplained. Traditionally, asthma epidemiology has focused on individual-level risk factors and family factors. Far less attention has been given to the broader social context in which individuals live. A multilevel approach that explicitly recognizes the embedding of asthma within its biological, psycho-socioeconomic, environmental, and community contexts, is likely to provide a better understanding of asthma disparities at different stages in the life course. Is it simply asthma disparities or is it social disparities in asthma?

Scientists find link between allergic and autoimmune diseases in mouse study

Cancer.gov

Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such as multiple sclerosis, asthma, Crohn's disease, ce

Methods of in-vivo mouse lung micro-CT

NASA Astrophysics Data System (ADS)

Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric

2005-04-01

Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated bronchial tree segmentation and airway wall thickness measurement tools. Improvements in Hounsfield unit calibration have to be performed when the interest of the study lies in determining and quantifying parenchymal changes and rely on estimating partial volume contributions of underlying structures to voxel densities.

Environmental triggers and avoidance in the management of asthma

PubMed Central

Gautier, Clarisse; Charpin, Denis

2017-01-01

Identifying asthma triggers forms the basis of environmental secondary prevention. These triggers may be allergenic or nonallergenic. Allergenic triggers include indoor allergens, such as house dust mites (HDMs), molds, pets, cockroaches, and rodents, and outdoor allergens, such as pollens and molds. Clinical observations provide support for the role of HDM exposure as a trigger, although avoidance studies provide conflicting results. Molds and their metabolic products are now considered to be triggers of asthma attacks. Pets, dogs, and especially cats can undoubtedly trigger asthmatic symptoms in sensitized subjects. Avoidance is difficult and rarely adhered to by families. Cockroach allergens contribute to asthma morbidity, and avoidance strategies can lead to clinical benefit. Mouse allergens are mostly found in inner-city dwellings, but their implication in asthma morbidity is debated. In the outdoors, pollens can induce seasonal asthma in sensitized individuals. Avoidance relies on preventing pollens from getting into the house and on minimizing seasonal outdoor exposure. Outdoor molds may lead to severe asthma exacerbations. Nonallergenic triggers include viral infections, active and passive smoking, meteorological changes, occupational exposures, and other triggers that are less commonly involved. Viral infection is the main asthma trigger in children. Active smoking is associated with higher asthma morbidity, and smoking cessation interventions should be personalized. Passive smoking is also a risk factor for asthma exacerbation. The implementation of public smoking bans has led to a reduction in the hospitalization of asthmatic children. Air pollution levels have been linked with asthmatic symptoms, a decrease in lung function, and increased emergency room visits and hospitalizations. Since avoidance is not easy to achieve, clean air policies remain the most effective strategy. Indoor air is also affected by air pollutants, such as cigarette smoke and volatile organic compounds generated by building and cleaning materials. Occupational exposures include work-exacerbated asthma and work-related asthma. PMID:28331347

The role of trait mindfulness in quality of life and asthma control among adolescents with asthma.

PubMed

Cillessen, Linda; van de Ven, Monique O; Karremans, Johan C

2017-08-01

The current study focused on the role of trait mindfulness in asthma-related quality of life (QoL) and asthma control in adolescent asthma patients. Furthermore, potential underlying mechanisms (general and asthma-specific stress) of this relationship were investigated. In this cross-sectional study, questionnaire data of 94 adolescents with asthma that were prescribed daily asthma medication were included. Two Structural Equation Models (SEMs), a direct model and an indirect model, were tested. We found that trait mindfulness was directly related to asthma-related QoL, but not to asthma control. The relationship between trait mindfulness and asthma-related QoL was explained by asthma-specific, but not by general stress. Furthermore, an indirect relation from mindfulness to asthma control via asthma-specific stress was found. Cross-sectional evidence for a relation between mindfulness and asthma-related QoL is found. These findings may point to the possibility that an intervention aimed at increasing mindfulness could be a promising tool to improve asthma-related QoL in adolescents via a decrease in asthma-specific stress. Copyright © 2017. Published by Elsevier Inc.

Blockade of IL-23 ameliorates allergic lung inflammation via decreasing the infiltration of Tc17 cells.

PubMed

Cheng, Sheng; Chen, Huilong; Wang, Aili; Bunjhoo, Hansvin; Cao, Yong; Xie, Jungang; Xu, Yongjian; Xiong, Weining

2016-12-01

Tc17 cells are interleukin (IL)-17-producing CD8 + T cells and have been found to participate in the development of allergic asthma. Interleukin-23 is a cytokine that may be involved in modulating the IL-17 response via Th17 cells. This study aimed to investigate whether IL-23 also has immunomodulatory effects on Tc17 cells. An allergic asthmatic mouse model was induced by sensitizing and challenging with ovalbumin (OVA). Anti-IL-23 antibody was administered intratracheally before challenge to the OVA-induced asthmatic mouse model. Airway hyperresponsiveness, lung inflammation, Tc17 cell percentages and IL-17 level in the lung tissue homogenate were measured. Anti-IL-23 treatment reduced airway hyperresponsiveness (Rn 2.471 ±0.5077 vs. 4.051 ±0.2334, p < 0.05), inflammatory cell infiltration in bronchoalveolar lavage fluid (eosinophils 140.0 ±9.869 vs. 222.4 ±31.55, p < 0.05, neutrophils 75.93 ±6.745 vs. 127.4 ±19.73, p < 0.05), airway inflammation and mucus secretion. Treatment with anti-IL-23 antibody also markedly reduced IL-17 level (398.1 ±28.74 vs. 590.6 ±36.13, p < 0.01) and percentage of Th17 and Tc17 cells in lung tissue homogenate (4.200 ±0.1581 vs. 9.314 ±1.027, p < 0.01 and 2.852 ±0.2566 vs. 5.588 ±0.3631, p < 0.01, Th17 and Tc17 cells respectively). Our data suggest that the IL-23/Tc17 cell axis may be involved in the pathogenesis of asthma as the complement of IL-23/Th17 cells.

Carica papaya ameliorates allergic asthma via down regulation of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS levels.

PubMed

Inam, Asma; Shahzad, Muhammad; Shabbir, Arham; Shahid, Hira; Shahid, Khadija; Javeed, Aqeel

2017-08-15

Natural products have a prime importance as an essential source for new drug discovery. Carica papaya leaves (CPL) have been used to treat inflammation in traditional system of medicine. Current study evaluates the anti-inflammatory and immunomodulatory effects of CPL extract using mouse model of ovalbumin- (OVA) induced allergic asthma. All the mice were intraperitoneally sensitized and subsequently given intranasal challenge with OVA except the control group. Group-III and -IV were treated for seven consecutive days with CPL extract and methylprednisolone (MP), respectively. At the end of study, histopathological examination of the lungs was performed and inflammatory cell counts were done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS were measured using reverse transcription polymerase chain reaction (RT-PCR). Results showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and goblet cell hyperplasia after treatment with CPL extract. We also found significant suppression of total and differential leukocyte counts in both blood and BALF samples of CPL extract treated group. CPL extract also alleviated the expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS. Similarly, treatment with MP, used as a reference drug, also significantly ameliorated all the pro-inflammatory markers. Current study shows that CPL extract possesses anti-inflammatory effect in mouse model of allergic airway inflammation by down-regulating IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS expression levels. Copyright © 2017 Elsevier GmbH. All rights reserved.

Quality of asthma care under different primary care models in Canada: a population-based study.

PubMed

To, Teresa; Guan, Jun; Zhu, Jingqin; Lougheed, M Diane; Kaplan, Alan; Tamari, Itamar; Stanbrook, Matthew B; Simatovic, Jacqueline; Feldman, Laura; Gershon, Andrea S

2015-02-14

Previous research has shown variations in quality of care and patient outcomes under different primary care models. The objective of this study was to use previously validated, evidence-based performance indicators to measure quality of asthma care over time and to compare quality of care between different primary care models. Data were obtained for years 2006 to 2010 from the Ontario Asthma Surveillance Information System, which uses health administrative databases to track individuals with asthma living in the province of Ontario, Canada. Individuals with asthma (n=1,813,922) were divided into groups based on the practice model of their primary care provider (i.e., fee-for-service, blended fee-for-service, blended capitation). Quality of asthma care was measured using six validated, evidence-based asthma care performance indicators. All of the asthma performance indicators improved over time within each of the primary care models. Compared to the traditional fee-for-service model, the blended fee-for-service and blended capitation models had higher use of spirometry for asthma diagnosis and monitoring, higher rates of inhaled corticosteroid prescription, and lower outpatient claims. Emergency department visits were lowest in the blended fee-for-service group. Quality of asthma care improved over time within each of the primary care models. However, the amount by which they improved differed between the models. The newer primary care models (i.e., blended fee-for-service, blended capitation) appear to provide better quality of asthma care compared to the traditional fee-for-service model.

A systematic review of predictive models for asthma development in children.

PubMed

Luo, Gang; Nkoy, Flory L; Stone, Bryan L; Schmick, Darell; Johnson, Michael D

2015-11-28

Asthma is the most common pediatric chronic disease affecting 9.6 % of American children. Delay in asthma diagnosis is prevalent, resulting in suboptimal asthma management. To help avoid delay in asthma diagnosis and advance asthma prevention research, researchers have proposed various models to predict asthma development in children. This paper reviews these models. A systematic review was conducted through searching in PubMed, EMBASE, CINAHL, Scopus, the Cochrane Library, the ACM Digital Library, IEEE Xplore, and OpenGrey up to June 3, 2015. The literature on predictive models for asthma development in children was retrieved, with search results limited to human subjects and children (birth to 18 years). Two independent reviewers screened the literature, performed data extraction, and assessed article quality. The literature search returned 13,101 references in total. After manual review, 32 of these references were determined to be relevant and are discussed in the paper. We identify several limitations of existing predictive models for asthma development in children, and provide preliminary thoughts on how to address these limitations. Existing predictive models for asthma development in children have inadequate accuracy. Efforts to improve these models' performance are needed, but are limited by a lack of a gold standard for asthma development in children.

Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples

PubMed Central

Dullin, Christian; dal Monego, Simeone; Larsson, Emanuel; Mohammadi, Sara; Krenkel, Martin; Garrovo, Chiara; Biffi, Stefania; Lorenzon, Andrea; Markus, Andrea; Napp, Joanna; Salditt, Tim; Accardo, Agostino; Alves, Frauke; Tromba, Giuliana

2015-01-01

Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites. PMID:25537601

Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation.

PubMed

Hansen, G; Berry, G; DeKruyff, R H; Umetsu, D T

1999-01-01

Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell-induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.

ADAM33 polymorphisms are associated with asthma and a distinctive palm dermatoglyphic pattern

PubMed Central

XUE, WEILIN; HAN, WEI; ZHOU, ZHAO-SHAN

2013-01-01

A close correlation between asthma and palm dermatoglyphic patterns has been observed in previous studies, but the underlying genetic mechanisms have not been investigated. A disintegrin and metalloprotein-33 (ADAM33) polymorphisms are important in the development of asthma and other atopic diseases. To investigate the underlying mechanisms of the association between asthma and distinctive palm dermatoglyphic patterns, thirteen ADAM33 single-nucleotide polymorphisms (SNPs) were analyzed for the association between asthma and palm dermatoglyphic patterns in a population of 400 asthmatic patients and 200 healthy controls. Based on the results, five SNPs, rs44707 (codominant model, P=0.031; log-additive model, P=0.0084), rs2787094 (overdominant model, P=0.049), rs678881 (codominant model, P=0.028; overdominant model, P=0.0083), rs677044 (codominant model, P=0.013; log-additive model, P=0.0033) and rs512625 (dominant model, P=0.033), were associated with asthma in this population. Two SNPs, rs44707 (dominant model, P=0.042) and rs2787094 (codominant model, P=0.014; recessive model, P=0.0038), were observed in the asthma patients with the distinctive palm pattern. As rs44707 and rs2787094 are associated with asthma and a distinctive palm pattern, the data suggest that ADAM33 polymorphisms are correlated with asthma and may be the underlying genetic basis of the association between asthma and palm dermatoglyphic patterns. PMID:24141861

The Effects of Maternal Exposure to Bisphenol A on Allergic Lung Inflammation into Adulthood

PubMed Central

Lawrence, B. Paige

2012-01-01

Bisphenol A (BPA) is a high–production volume chemical classified as an environmental estrogen and used primarily in the plastics industry. BPA’s increased usage correlates with rising BPA levels in people and a corresponding increase in the incidence of asthma. Due to limited studies, the contribution of maternal BPA exposure to allergic asthma pathogenesis is unclear. Using two established mouse models of allergic asthma, we examined whether developmental exposure to BPA alters hallmarks of allergic lung inflammation in adult offspring. Pregnant C57BL/6 dams were gavaged with 0, 0.5, 5, 50, or 500 μg BPA/kg/day from gestational day 6 until postnatal day 21. To induce allergic inflammation, adult offspring were mucosally sensitized with inhaled ovalbumin containing low-dose lipopolysaccharide or ip sensitized using ovalbumin with alum followed by ovalbumin aerosol challenge. In the mucosal sensitization model, female offspring that were maternally exposed to ≥ 50 μg BPA/kg/day displayed enhanced airway lymphocytic and lung inflammation, compared with offspring of control dams. Peritoneally sensitized, female offspring exposed to ≤ 50 μg BPA/kg/day presented dampened lung eosinophilia, compared with vehicle controls. Male offspring did not exhibit these differences in either sensitization model. Our data demonstrate that maternal exposure to BPA has subtle and qualitatively different effects on allergic inflammation, which are critically dependent upon route of allergen sensitization and sex. However, these subtle, yet persistent changes due to developmental exposure to BPA did not lead to significant differences in overall airway responsiveness, suggesting that early life exposure to BPA does not exacerbate allergic inflammation into adulthood. PMID:22821851

Phosphoinositide 3-kinase gamma regulates airway smooth muscle contraction by modulating calcium oscillations.

PubMed

Jiang, Haihong; Abel, Peter W; Toews, Myron L; Deng, Caishu; Casale, Thomas B; Xie, Yan; Tu, Yaping

2010-09-01

Phosphoinositide 3-kinase gamma (PI3Kgamma) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kgamma can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kgamma protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kgamma inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 muM. In contrast, inhibitors of PI3Kalpha, PI3Kbeta, or PI3Kdelta, at concentrations 40-fold higher than their reported IC(50) values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kgamma inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kgamma-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca(2+) transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca(2+) oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kgamma directly controls contractility of airways through regulation of Ca(2+) oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kgamma inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness.

Phosphoinositide 3-Kinase γ Regulates Airway Smooth Muscle Contraction by Modulating Calcium Oscillations

PubMed Central

Jiang, Haihong; Abel, Peter W.; Toews, Myron L.; Deng, Caishu; Casale, Thomas B.; Xie, Yan

2010-01-01

Phosphoinositide 3-kinase γ (PI3Kγ) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kγ can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kγ protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kγ inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 μM. In contrast, inhibitors of PI3Kα, PI3Kβ, or PI3Kδ, at concentrations 40-fold higher than their reported IC50 values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kγ inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kγ-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca2+ transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca2+ oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kγ directly controls contractility of airways through regulation of Ca2+ oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kγ inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness. PMID:20501633

Effect of Weatherization Combined With Community Health Worker In-Home Education on Asthma Control

PubMed Central

Dixon, Sherry; Gregory, Joel; Philby, Miriam; Jacobs, David E.; Krieger, James

2014-01-01

Objectives. We assessed the benefits of adding weatherization-plus-health interventions to an in-home, community health worker (CHW) education program on asthma control. Methods. We used a quasi-experimental design to compare study group homes (n = 34) receiving CHW education and weatherization-plus-health structural interventions with historical comparison group homes (n = 68) receiving only education. Data were collected in King County, Washington, from October 2009 to September 2010. Results. Over the 1-year study period, the percentage of study group children with not-well-controlled or very poorly controlled asthma decreased more than the comparison group percentage (100% to 28.8% vs 100% to 51.6%; P = .04). Study group caregiver quality-of-life improvements exceeded comparison group improvements (P = .002) by 0.7 units, a clinically important difference. The decrease in study home asthma triggers (evidence of mold, water damage, pests, smoking) was marginally greater than the comparison group decrease (P = .089). Except for mouse allergen, the percentage of study group allergen floor dust samples at or above the detection limit decreased, although most reductions were not statistically significant. Conclusions. Combining weatherization and healthy home interventions (e.g., improved ventilation, moisture and mold reduction, carpet replacement, and plumbing repairs) with CHW asthma education significantly improves childhood asthma control. PMID:24228661

[Vaccination with Mycobacterium: can it cure allergies?].

PubMed

Louis, R

2003-06-01

In developed countries, the prevalence of tuberculosis has evolved in an opposite direction as to the one of allergy over the last century. The immunological response is mainly Th1 in tuberculosis while it features a Th2 pattern in allergy. Vaccination with BCG in early life is associated with a reduction in the prevalence of allergy later in childhood. In an experimental mouse model of asthma, administration of BCG or killed Mycobacterium vaccae inhibits the sensitisation process as well as the bronchial inflammation and hyperresponsiveness that follows allergen exposure. In children and adolescents suffering from atopic dermatitis, subcutaneous injection of killed Mycobacterium vaccae attenuates the severity of skin lesions.

Features of asthma which provide meaningful insights for understanding the disease heterogeneity.

PubMed

Deliu, M; Yavuz, T S; Sperrin, M; Belgrave, D; Sahiner, U M; Sackesen, C; Kalayci, O; Custovic, A

2018-01-01

Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

PubMed Central

Yarova, Polina L.; Stewart, Alecia L.; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A.; Lowe, Alexander P. P.; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C.; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J.; Ford, William R.; Broadley, Kenneth J.; Rietdorf, Katja; Chang, Wenhan; Khayat, Mohd E. Bin; Ward, Donald T.; Corrigan, Christopher J.; Ward, Jeremy P. T.; Kemp, Paul J.; Pabelick, Christina M.; Prakash, Y. S.; Riccardi, Daniela

2016-01-01

Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyper-reactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744

Monitoring asthma control in children with allergies by soft computing of lung function and exhaled nitric oxide.

PubMed

Pifferi, Massimo; Bush, Andrew; Pioggia, Giovanni; Di Cicco, Maria; Chinellato, Iolanda; Bodini, Alessandro; Macchia, Pierantonio; Boner, Attilio L

2011-02-01

Asthma control is emphasized by new guidelines but remains poor in many children. Evaluation of control relies on subjective patient recall and may be overestimated by health-care professionals. This study assessed the value of spirometry and fractional exhaled nitric oxide (FeNO) measurements, used alone or in combination, in models developed by a machine learning approach in the objective classification of asthma control according to Global Initiative for Asthma guidelines and tested the model in a second group of children with asthma. Fifty-three children with persistent atopic asthma underwent two to six evaluations of asthma control, including spirometry and FeNO. Soft computing evaluation was performed by means of artificial neural networks and principal component analysis. The model was then tested in a cross-sectional study in an additional 77 children with allergic asthma. The machine learning method was not able to distinguish different levels of control using either spirometry or FeNO values alone. However, their use in combination modeled by soft computing was able to discriminate levels of asthma control. In particular, the model is able to recognize all children with uncontrolled asthma and correctly identify 99.0% of children with totally controlled asthma. In the cross-sectional study, the model prospectively identified correctly all the uncontrolled children and 79.6% of the controlled children. Soft computing analysis of spirometry and FeNO allows objective categorization of asthma control status.

IgE Immune Complexes Stimulate an Increase in Lung Mast Cell Progenitors in a Mouse Model of Allergic Airway Inflammation

PubMed Central

Dahlin, Joakim S.; Ivarsson, Martin A.; Heyman, Birgitta; Hallgren, Jenny

2011-01-01

Mast cell numbers and allergen specific IgE are increased in the lungs of patients with allergic asthma and this can be reproduced in mouse models. The increased number of mast cells is likely due to recruitment of mast cell progenitors that mature in situ. We hypothesized that formation of IgE immune complexes in the lungs of sensitized mice increase the migration of mast cell progenitors to this organ. To study this, a model of allergic airway inflammation where mice were immunized with ovalbumin (OVA) in alum twice followed by three daily intranasal challenges of either OVA coupled to trinitrophenyl (TNP) alone or as immune complexes with IgE-anti-TNP, was used. Mast cell progenitors were quantified by a limiting dilution assay. IgE immune complex challenge of sensitized mice elicited three times more mast cell progenitors per lung than challenge with the same dose of antigen alone. This dose of antigen challenge alone did not increase the levels of mast cell progenitors compared to unchallenged mice. IgE immune complex challenge of sensitized mice also enhanced the frequency of mast cell progenitors per 106 mononuclear cells by 2.1-fold. The enhancement of lung mast cell progenitors by IgE immune complex challenge was lost in FcRγ deficient mice but not in CD23 deficient mice. Our data show that IgE immune complex challenge enhances the number of mast cell progenitors in the lung through activation of an Fc receptor associated with the FcRγ chain. This most likely takes place via activation of FcεRI, although activation via FcγRIV or a combination of the two receptors cannot be excluded. IgE immune complex-mediated enhancement of lung MCp numbers is a new reason to target IgE in therapies against allergic asthma. PMID:21625525

1alpha,25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta.

PubMed

Taher, Yousef A; van Esch, Betty C A M; Hofman, Gerard A; Henricks, Paul A J; van Oosterhout, Antoon J M

2008-04-15

1alpha,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a potent inhibitor of NF-kappaB expression, can prevent the maturation of dendritic cells in vitro leading to tolerogenic dendritic cells with increased potential to induce regulatory T cells. Herein, we investigated whether the combination of allergen immunotherapy with 1,25(OH)(2)D(3) potentiates the suppressive effects of immunotherapy and whether the immunoregulatory cytokines IL-10 and TGF-beta are involved in the effector phase. OVA-sensitized and challenged BALB/c mice displayed airway hyperresponsiveness (AHR) and increased serum OVA-specific IgE levels, bronchoalveolar lavage eosinophilia, and Th2 cytokine levels. In this model, the dose response of allergen immunotherapy 10 days before OVA inhalation challenge shows strong suppression of asthma manifestations at 1 mg of OVA, but partial suppression of bronchoalveolar lavage eosinophilia, IgE up-regulation, and no reduction of AHR at 100 microg. Interestingly, coadministration of 10 ng of 1,25(OH)(2)D(3) with 100 microg of OVA immunotherapy significantly inhibited AHR and potentiated the reduction of serum OVA-specific IgE levels, airway eosinophilia, and Th2-related cytokines concomitant with increased IL-10 levels in lung tissues and TGF-beta and OVA-specific IgA levels in serum. Similar effects on suboptimal immunotherapy were observed by inhibition of the NF-kappaB pathway using the selective IkappaB kinase 2 inhibitor PS-1145. The suppressive effects of this combined immunotherapy were partially reversed by treatment with mAb to either IL-10R or TGF-beta before OVA inhalation challenge but completely abrogated when both Abs were given. These data demonstrate that 1,25(OH)(2)D(3) potentiates the efficacy of immunotherapy and that the regulatory cytokines IL-10 and TGF-beta play a crucial role in the effector phase of this mouse model.

Fungal exposure, atopy, and asthma exacerbations in Puerto Rican children.

PubMed

Blatter, Joshua; Forno, Erick; Brehm, John; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Thorne, Peter S; Metwali, Nervana; Canino, Glorisa; Celedón, Juan C

2014-07-01

Glucan is a component of the fungal cell wall that is used as a marker of fungal exposure. Little is known about indoor glucan, atopy, and asthma exacerbations among children living in tropical environments such as Puerto Rico. Our objective was to examine whether glucan exposure is associated with degree of atopy or visits to the emergency department (ED)/urgent care for asthma in Puerto Rican children. This was a cross-sectional study of 317 children aged 6 to 14 years with (cases, n = 160) and without (control subjects, n = 157) asthma in San Juan, Puerto Rico. Our primary outcomes were the number of positive skin tests to allergens (range, 0-15) and (in cases only) having had at least one visit to the ED/urgent care for asthma in the prior year. Levels of glucan, endotoxin, peptidoglycan, and five allergens (Der p 1, Bla g 2, Fel d 1, Can f 1, and Mus m 1) were measured in samples of house dust. Linear or logistic regression was used for the multivariate analysis. In a multivariate analysis adjusting for case-control status, mouse allergen, and other covariates, children exposed to glucan levels in the second and third quartiles had approximately two more positive skin tests than those in the lowest quartile (P < 0.01 in both instances). Among children with asthma, exposure to the highest quartile of glucan was associated with nearly ninefold greater odds of one or more visits to the ED/urgent care for asthma (95% confidence interval for adjusted odds ratio, 2.7-28.4; P < 0.001). Our results suggest that indoor fungal exposure leads to an increased degree of atopy and visits to the ED/urgent care for asthma in Puerto Rican children.

Fungal Exposure, Atopy, and Asthma Exacerbations in Puerto Rican Children

PubMed Central

Blatter, Joshua; Forno, Erick; Brehm, John; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Thorne, Peter S.; Metwali, Nervana; Canino, Glorisa

2014-01-01

Background: Glucan is a component of the fungal cell wall that is used as a marker of fungal exposure. Little is known about indoor glucan, atopy, and asthma exacerbations among children living in tropical environments such as Puerto Rico. Our objective was to examine whether glucan exposure is associated with degree of atopy or visits to the emergency department (ED)/urgent care for asthma in Puerto Rican children. Methods: This was a cross-sectional study of 317 children aged 6 to 14 years with (cases, n = 160) and without (control subjects, n = 157) asthma in San Juan, Puerto Rico. Our primary outcomes were the number of positive skin tests to allergens (range, 0–15) and (in cases only) having had at least one visit to the ED/urgent care for asthma in the prior year. Levels of glucan, endotoxin, peptidoglycan, and five allergens (Der p 1, Bla g 2, Fel d 1, Can f 1, and Mus m 1) were measured in samples of house dust. Linear or logistic regression was used for the multivariate analysis. Measurements and Main Results: In a multivariate analysis adjusting for case-control status, mouse allergen, and other covariates, children exposed to glucan levels in the second and third quartiles had approximately two more positive skin tests than those in the lowest quartile (P < 0.01 in both instances). Among children with asthma, exposure to the highest quartile of glucan was associated with nearly ninefold greater odds of one or more visits to the ED/urgent care for asthma (95% confidence interval for adjusted odds ratio, 2.7–28.4; P < 0.001). Conclusions: Our results suggest that indoor fungal exposure leads to an increased degree of atopy and visits to the ED/urgent care for asthma in Puerto Rican children. PMID:24915164

Thrombomodulin inhibits the activation of eosinophils and mast cells.

PubMed

Roeen, Ziaurahman; Toda, Masaaki; D'Alessandro-Gabazza, Corina N; Onishi, Masahiro; Kobayashi, Tetsu; Yasuma, Taro; Urawa, Masahito; Taguchi, Osamu; Gabazza, Esteban C

2015-01-01

Eosinophils and mast cells play critical roles in the pathogenesis of bronchial asthma. Activation of both cells leads to the release of pro-inflammatory mediators in the airway of asthmatic patients. Recently, we have shown that inhaled thrombomodulin inhibits allergic bronchial asthma in a mouse model. In the present study, we hypothesize that thrombomodulin can inhibit the activation of eosinophils and mast cells. The effect of thrombomodulin on the activation and release of inflammatory mediators from eosinophils and mast cells was evaluated. Thrombomodulin inhibited the eotaxin-induced chemotaxis, upregulation of CD11b and degranulation of eosinophils. Treatment with thrombomodulin also significantly suppressed the degranulation and synthesis of inflammatory cytokines and chemokines in eosinophils and mast cells. Mice treated with a low-dose of inhaled thrombomodulin have decreased number of eosinophils and activated mast cells and Th2 cytokines in the lungs compared to untreated mice. The results of this study suggest that thrombomodulin may modulate allergic responses by inhibiting the activation of both eosinophils and mast cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness.

PubMed

Kirstein, Frank; Nieuwenhuizen, Natalie E; Jayakumar, Jaisubash; Horsnell, William G C; Brombacher, Frank

2016-06-01

TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood. This study defines the requirements for IL-4Rα-responsive CD4(+) T cells and the IL-4Rα ligands IL-4 and IL-13 in the development of allergen-specific TH2 responses during the onset and chronic phase of experimental allergic airway disease. Development of acute and chronic ovalbumin (OVA)-induced allergic asthma was assessed weekly in CD4(+) T cell-specific IL-4Rα-deficient BALB/c mice (Lck(cre)IL-4Rα(-/lox)) and respective control mice in the presence or absence of IL-4 or IL-13. During acute allergic airway disease, IL-4 deficiency did not prevent the onset of TH2 immune responses and OVA-induced airway hyperresponsiveness or goblet cell hyperplasia, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. In contrast, deficiency of IL-13 prevented allergic asthma, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. Importantly, chronic allergic inflammation and airway hyperresponsiveness were dependent on IL-4Rα-responsive CD4(+) T cells. Deficiency in IL-4Rα-responsive CD4(+) T cells resulted in increased numbers of IL-17-producing T cells and, consequently, increased airway neutrophilia. IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Assessment of variations in control of asthma over time.

PubMed

Combescure, C; Chanez, P; Saint-Pierre, P; Daurès, J P; Proudhon, H; Godard, P

2003-08-01

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment

PubMed Central

Tang, Guan-Nan; Li, Cheng-Lin; Yao, Yin; Xu, Zhi-Bin; Deng, Meng-Xia; Wang, Shu-Yue; Sun, Yue-Qi; Shi, Jian-Bo

2016-01-01

Administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) significantly alleviates allergic airway inflammation. There are no studies that refer to the role of microRNAs (miRNAs) after the BM-MSCs treatment in airway allergic inflammation. We induced a mouse model of asthma and performed the transplantation of BM-MSCs. We analyzed aberrant miRNAs and key immune regulators using both miRNA and messenger RNA (mRNA) polymerase chain reaction (PCR) arrays. We identified that 296 miRNAs were differently expressed after the induction of asthma and/or the treatment of BM-MSCs, in which 14 miRNAs presented the reverse variation tendency between asthma induction and BM-MSCs transplantation. Mmu-miR-21a-3p, mmu-miR-449c-5p, and mmu-miR-496a-3p were further confirmed to be differently expressed with additional samples and quantitative real-time PCR. With an mRNA PCR array, we identified 19 genes to be involved in the allergy induction and the administration of BM-MSCs. Further target genes analysis revealed that mmu-miR-21a-3p was significantly correlated with the immune regulator activin A receptor, Type IIA (Acvr2a). Mmu-miR-21a-3p had opposite expression with Acvr2a after asthma and BM-MSCs treatment. Acvr2a had binding sites for miR-21a for both mice and human, suggesting that miR-21/Acvr2a axis is conserved between human and mice. Dual-luciferase reporter assay showed that mmu-miR-21a-3p negatively regulated the transcript of Acvr2a. In addition, has-miR-21a inhibitor significantly increased the expression of Acvr2a mRNA in BEAS-2B cells under lipopolysaccharide stimulation. Our results suggest that there were different miRNA and mRNA profiles after asthma induction and BM-MSCs treatment, and the miR-21/Acvr2a axis is an important mechanism for the induction of asthmatic inflammation. PMID:27106170

Role of community pharmacists in asthma - Australian research highlighting pathways for future primary care models.

PubMed

Saini, B; Krass, I; Smith, L; Bosnic-Anticevich, S; Armour, C

2011-01-01

Asthma is one of the most common chronic conditions affecting the Australian population. Amongst primary healthcare professionals, pharmacists are the most accessible and this places pharmacists in an excellent position to play a role in the management of asthma. Globally, trials of many community pharmacy-based asthma care models have provided evidence that pharmacist delivered interventions can improve clinical, humanistic and economic outcomes for asthma patients. In Australia, a decade of coordinated research efforts, in various aspects of asthma care, has culminated in the implementation trial of the Pharmacy Asthma Management Service (PAMS), a comprehensive disease management model.There has been research investigating asthma medication adherence through data mining, ways in which usual asthma care can be improved. Our research has focused on self-management education, inhaler technique interventions, spirometry trials, interprofessional models of care, and regional trials addressing the particular needs of rural communities. We have determined that inhaler technique education is a necessity and should be repeated if correct technique is to be maintained. We have identified this effectiveness of health promotion and health education, conducted within and outside the confines of the pharmacy, in public for a and settings such as schools, and established that this outreach role is particularly well received and increases the opportunity for people with asthma to engage in their asthma management.Our research has identified that asthma patients have needs which pharmacists delivering specialized models of care, can address. There is a lot of evidence for the effectiveness of asthma care by pharmacists, the future must involve integration of this role into primary care.

A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle Constriction and Inflammation by Targeting GABAA Receptors in the Lung.

PubMed

Forkuo, Gloria S; Nieman, Amanda N; Kodali, Revathi; Zahn, Nicolas M; Li, Guanguan; Rashid Roni, M S; Stephen, Michael Rajesh; Harris, Ted W; Jahan, Rajwana; Guthrie, Margaret L; Yu, Olivia B; Fisher, Janet L; Yocum, Gene T; Emala, Charles W; Steeber, Douglas A; Stafford, Douglas C; Cook, James M; Arnold, Leggy A

2018-05-07

We describe lead compound MIDD0301 for the oral treatment of asthma based on previously developed positive allosteric α 5 β 3 γ 2 selective GABA A receptor (GABA A R) ligands. MIDD0301 relaxed airway smooth muscle at single micromolar concentrations as demonstrated with ex vivo guinea pig tracheal rings. MIDD0301 also attenuated airway hyperresponsiveness (AHR) in an ovalbumin murine model of asthma by oral administration. Reduced numbers of eosinophils and macrophages were observed in mouse bronchoalveolar lavage fluid without changing mucous metaplasia. Importantly, lung cytokine expression of IL-17A, IL-4, and TNF-α were reduced for MIDD0301-treated mice without changing antiinflammatory cytokine IL-10 levels. Automated patch clamp confirmed amplification of GABA induced current mediated by α 1-3,5 β 3 γ 2 GABA A Rs in the presence of MIDD0301. Pharmacodynamically, transmembrane currents of ex vivo CD4 + T cells from asthmatic mice were potentiated by MIDD0301 in the presence of GABA. The number of CD4 + T cells observed in the lung of MIDD0301-treated mice were reduced by an oral treatment of 20 mg/kg b.i.d. for 5 days. A half-life of almost 14 h was demonstrated by pharmacokinetic studies (PK) with no adverse CNS effects when treated mice were subjected to sensorimotor studies using the rotarod. PK studies also confirmed very low brain distribution. In conclusion, MIDD0301 represents a safe and improved oral asthma drug candidate that relaxes airway smooth muscle and attenuates inflammation in the lung leading to a reduction of AHR at a dosage lower than earlier reported GABA A R ligands.

Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences.

PubMed

Martinez, Fernando O; Helming, Laura; Milde, Ronny; Varin, Audrey; Melgert, Barbro N; Draijer, Christina; Thomas, Benjamin; Fabbri, Marco; Crawshaw, Anjali; Ho, Ling Pei; Ten Hacken, Nick H; Cobos Jiménez, Viviana; Kootstra, Neeltje A; Hamann, Jörg; Greaves, David R; Locati, Massimo; Mantovani, Alberto; Gordon, Siamon

2013-02-28

The molecular repertoire of macrophages in health and disease can provide novel biomarkers for diagnosis, prognosis, and treatment. Th2-IL-4–activated macrophages (M2) have been associated with important diseases in mice, yet no specific markers are available for their detection in human tissues. Although mouse models are widely used for macrophage research, translation to the human can be problematic and the human macrophage system remains poorly described. In the present study, we analyzed and compared the transcriptome and proteome of human and murine macrophages under resting conditions (M0) and after IL-4 activation (M2). We provide a resource for tools enabling macrophage detection in human tissues by identifying a set of 87 macrophage-related genes. Furthermore, we extend current understanding of M2 activation in different species and identify Transglutaminase 2 as a conserved M2 marker that is highly expressed by human macrophages and monocytes in the prototypic Th2 pathology asthma.

Comparison of Airway Responses Induced in a Mouse Model by the Gas and Particulate Fractions of Gasoline Direct Injection Engine Exhaust.

PubMed

Maikawa, Caitlin L; Zimmerman, Naomi; Ramos, Manuel; Shah, Mittal; Wallace, James S; Pollitt, Krystal J Godri

2018-03-01

Diesel exhaust has been associated with asthma, but its response to other engine emissions is not clear. The increasing prevalence of vehicles with gasoline direct injection (GDI) engines motivated this study, and the objective was to evaluate pulmonary responses induced by acute exposure to GDI engine exhaust in an allergic asthma murine model. Mice were sensitized with an allergen to induce airway hyperresponsiveness or treated with saline (non-allergic group). Animals were challenged for 2-h to exhaust from a laboratory GDI engine operated at conditions equivalent to a highway cruise. Exhaust was filtered to assess responses induced by the particulate and gas fractions. Short-term exposure to particulate matter from GDI engine exhaust induced upregulation of genes related to polycyclic aromatic hydrocarbon (PAH) metabolism ( Cyp1b1 ) and inflammation ( TNFα ) in the lungs of non-allergic mice. High molecular weight PAHs dominated the particulate fraction of the exhaust, and this response was therefore likely attributable to the presence of these PAHs. The particle fraction of GDI engine exhaust further contributed to enhanced methacholine responsiveness in the central and peripheral tissues in animals with airway hyperresponsiveness. As GDI engines gain prevalence in the vehicle fleet, understanding the health impacts of their emissions becomes increasingly important.

Comparison of Airway Responses Induced in a Mouse Model by the Gas and Particulate Fractions of Gasoline Direct Injection Engine Exhaust

PubMed Central

Maikawa, Caitlin L.; Zimmerman, Naomi; Ramos, Manuel; Wallace, James S.; Pollitt, Krystal J. Godri

2018-01-01

Diesel exhaust has been associated with asthma, but its response to other engine emissions is not clear. The increasing prevalence of vehicles with gasoline direct injection (GDI) engines motivated this study, and the objective was to evaluate pulmonary responses induced by acute exposure to GDI engine exhaust in an allergic asthma murine model. Mice were sensitized with an allergen to induce airway hyperresponsiveness or treated with saline (non-allergic group). Animals were challenged for 2-h to exhaust from a laboratory GDI engine operated at conditions equivalent to a highway cruise. Exhaust was filtered to assess responses induced by the particulate and gas fractions. Short-term exposure to particulate matter from GDI engine exhaust induced upregulation of genes related to polycyclic aromatic hydrocarbon (PAH) metabolism (Cyp1b1) and inflammation (TNFα) in the lungs of non-allergic mice. High molecular weight PAHs dominated the particulate fraction of the exhaust, and this response was therefore likely attributable to the presence of these PAHs. The particle fraction of GDI engine exhaust further contributed to enhanced methacholine responsiveness in the central and peripheral tissues in animals with airway hyperresponsiveness. As GDI engines gain prevalence in the vehicle fleet, understanding the health impacts of their emissions becomes increasingly important. PMID:29494515

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells.

PubMed

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

PubMed Central

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P.; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M.; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders. PMID:28861085

Quantification of Chitinase mRNA Levels in Human and Mouse Tissues by Real-Time PCR: Species-Specific Expression of Acidic Mammalian Chitinase in Stomach Tissues

PubMed Central

Ohno, Misa; Togashi, Yuto; Tsuda, Kyoko; Okawa, Kazuaki; Kamaya, Minori; Sakaguchi, Masayoshi; Sugahara, Yasusato; Oyama, Fumitaka

2013-01-01

Chitinase hydrolyzes chitin, which is an N-acetyl-D-glucosamine polymer that is present in a wide range of organisms, including insects, parasites and fungi. Although mammals do not contain any endogenous chitin, humans and mice express two active chitinases, chitotriosidase (Chit1) and acidic mammalian chitinase (AMCase). Because the level of expression of these chitinases is increased in many inflammatory conditions, including Gaucher disease and mouse models of asthma, both chitinases may play important roles in the pathophysiologies of these and other diseases. We recently established a quantitative PCR system using a single standard DNA and showed that AMCase mRNA is synthesized at extraordinarily high levels in mouse stomach tissues. In this study, we applied this methodology to the quantification of chitinase mRNAs in human tissues and found that both chitinase mRNAs were widely expressed in normal human tissues. Chit1 mRNA was highly expressed in the human lung, whereas AMCase mRNA was not overexpressed in normal human stomach tissues. The levels of these mRNAs in human tissues were significantly lower than the levels of housekeeping genes. Because the AMCase expression levels were quite different between the human and mouse stomach tissues, we developed a quantitative PCR system to compare the mRNA levels between human and mouse tissues using a human-mouse hybrid standard DNA. Our analysis showed that Chit1 mRNA is expressed at similar levels in normal human and mouse lung. In contrast, the AMCase expression level in human stomach was significantly lower than that expression level observed in mouse stomach. These mRNA differences between human and mouse stomach tissues were reflecting differences in the chitinolytic activities and levels of protein expression. Thus, the expression level of the AMCase in the stomach is species-specific. PMID:23826286

Glycyrrhizin and long-term histopathologic changes in a murine model of asthma.

PubMed

Hocaoglu, Arzu Babayigit; Karaman, Ozkan; Erge, Duygu Olmez; Erbil, Guven; Yilmaz, Osman; Bagriyanik, Alper; Uzuner, Nevin

2011-12-01

Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) μm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) μm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 μm(2); and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 μm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers (P < 0.001 for all) in the asthma group compared with in the control group. The number of goblet (P < 0.001) and mast (P < 0.02) cells and the thickness of basement membrane (P < 0.001), subepithelial smooth muscle layers (P ≤ 0.001), and epithelium of the lung (P < 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was no statistically significant difference between the 2 groups in the histopathologic parameters, including thickness of basement membrane (P = 0.514), subepithelial smooth muscle (P = 0.054), and epithelium (P = 1.0) and number of mast (P = 0.075) and goblet (P = 0.988) cells. The results of this study suggest that the group receiving glycyrrhizin had amelioration of all established chronic histopathologic changes of lung in the mouse model of asthma. Further studies are needed to evaluate the efficacy of glycyrrhizin in the management of asthma.

Induced trefoil factor family 1 expression by trans-differentiating Clara cells in a murine asthma model.

PubMed

Kouznetsova, Irina; Chwieralski, Caroline E; Bälder, Ralf; Hinz, Margitta; Braun, Armin; Krug, Norbert; Hoffmann, Werner

2007-03-01

Asthma is a chronic inflammatory disease of the airways that is accompanied by goblet cell metaplasia and mucus hypersecretion. Trefoil factor family (TFF) peptides represent major secretory products of the respiratory tract and are synthesized together with mucins. In the murine lung, TFF2 is mainly expressed, whereas TFF1 transcripts represent only a minor species. TFF peptides are well known for their motogenic and anti-apoptotic effects, and they modulate the inflammatory response of bronchial epithelial cells. Here, an established mouse model of asthma was investigated (i.e., exposure to Aspergillus fumigatus [AF] antigens). RT-PCR analysis of lung tissue showed elevated levels particularly of TFF1 transcripts in AF-sensitized/challenged animals. In contrast, transcripts encoding Clara cell secretory protein (CCSP/CC10) were strongly diminished in these animals. For comparison, the expression of the goblet cell secretory granule marker mCLCA3/Gob-5, the mucins Muc1-Muc6 and Muc19, and the secretoglobins ScgB3A1 and ScgB3A2, as well as the mammalian ependymin-related gene MERP2, were monitored. Immunohistochemistry localized TFF1 mainly in cells with a mixed phenotype (e.g., TFF1-positive cells stain with the lectin wheat germ agglutinin (WGA), which recognizes mucins characteristic of goblet cells). In addition, these cells express CCSP/CC10, a Clara cell marker. When compared with mucins or CCSP/CC10, TFF1 was stored in a different population of secretory granules localized at the more basolateral portion of these cells. Thus, the results presented indicate for the first time that allergen exposure leads to the trans-differentiation of Clara cells toward a TFF1-expressing mucous phenotype.

Effect of oral tolerance in a mouse model of allergic rhinitis.

PubMed

Shin, Ji-Hyeon; Kang, Jun Myung; Kim, Sung Won; Cho, Jin-Hee; Park, Yong Jin; Kim, Soo Whan

2010-03-01

Induction of oral tolerance (OT) is known to prevent allergic inflammation in models of asthma. This study investigated the preventive effect of OT and airway remodeling in a mouse model of allergic rhinitis (AR). An in vivo study using an animal model. Catholic Research Institutes of Medical Science. Forty six-week-old, female BALB/c mice were divided into four groups: control, AR, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/aluminum hydroxide, 1 mg for six days in the low-dose OT group and a 25 mg single dose in the high-dose OT group. Mice in the AR group were fed phosphate-buffered saline. After sensitization followed by challenges with OVA during six weeks, nasal behaviors, interleukin (IL)-13 and interferon gamma (IFN-gamma) levels in nasal lavage (NAL) fluids, as well as OVA-specific IgE levels in serum, were measured. The degree of goblet cell hyperplasia and thickness of lamina propria were observed in nasal tissues by periodic acid-Schiff and Masson's trichrome stain. A P value < 0.05 was accepted as statistically significant. Both OT groups showed a significant decrease in inflammatory cells, IL-13 and IFN-gamma in NAL fluids, as well as OVA-specific IgE levels in serum compared with the AR group. In addition, the degree of goblet cell hyperplasia and thickness of lamina propria were attenuated in both OT groups compared with the AR group. Further, these alterations did not differ significantly between the two OT groups. These results suggest that OT may effectively reduce allergic inflammation as well as airway remodeling in a mouse model of AR. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Mediating pathways from central obesity to childhood asthma: a population-based longitudinal study.

PubMed

Chih, An-Hsuan; Chen, Yang-Ching; Tu, Yu-Kang; Huang, Kuo-Chin; Chiu, Tai-Yuan; Lee, Yungling Leo

2016-09-01

The mediating pathways linking obesity and asthma are largely unknown. We aimed to investigate the mediating pathways and to search for the most prominent pathological mechanism between central obesity and childhood asthma.In the Taiwan Children Health Study, we collected data on an open cohort of children aged 9-13 years. Children's respiratory outcomes, atopic conditions, obesity measures and pulmonary function were surveyed annually between 2010 and 2012. Exhaled nitric oxide fraction concentrations were recorded in 2012. Generalised estimating equations and general linear models were used to examine the associations between central obesity, possible mediators and asthma. Structural equation models were applied to investigate the pathways that mediate the link between central obesity and asthma.Central obesity (waist-to-hip ratio) most accurately predicted childhood asthma. In the active asthma model, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy and 5.7% for airway inflammation. The percentage of mediation for pulmonary function was 40.2% in the lifetime wheeze model. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models.Decline in pulmonary function is the most important pathway in central obesity related asthma. Pulmonary function screening should be applied to obese children for asthma risk prediction. Copyright ©ERS 2016.

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus

PubMed Central

Melo, Rossana C. N.; Duan, Susu; LeMessurier, Kim S.; Liedmann, Swantje; Surman, Sherri L.; Lee, James J.; Hurwitz, Julia L.; Thomas, Paul G.; McCullers, Jonathan A.

2017-01-01

Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus–infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8+ T cell numbers in the airways. In vitro assays with primary or bone marrow–derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide–exposed eosinophils induced CD8+ T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. PMID:28283567

Human versus mouse eosinophils: "that which we call an eosinophil, by any other name would stain as red".

PubMed

Lee, James J; Jacobsen, Elizabeth A; Ochkur, Sergei I; McGarry, Michael P; Condjella, Rachel M; Doyle, Alfred D; Luo, Huijun; Zellner, Katie R; Protheroe, Cheryl A; Willetts, Lian; Lesuer, William E; Colbert, Dana C; Helmers, Richard A; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A

2012-09-01

The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Are neighborhood-level characteristics associated with indoor allergens in the household?

PubMed

Rosenfeld, Lindsay; Rudd, Rima; Chew, Ginger L; Emmons, Karen; Acevedo-García, Dolores

2010-02-01

Individual home characteristics have been associated with indoor allergen exposure; however, the influence of neighborhood-level characteristics has not been well studied. We defined neighborhoods as community districts determined by the New York City Department of City Planning. We examined the relationship between neighborhood-level characteristics and the presence of dust mite (Der f 1), cat (Fel d 1), cockroach (Bla g 2), and mouse (MUP) allergens in the household. Using data from the Puerto Rican Asthma Project, a birth cohort of Puerto Rican children at risk of allergic sensitization (n = 261), we examined associations between neighborhood characteristics (percent tree canopy, asthma hospitalizations per 1,000 children, roadway length within 100 meters of buildings, serious housing code violations per 1000 rental units, poverty rates, and felony crime rates), and the presence of indoor allergens. Allergen cutpoints were used for categorical analyses and defined as follows: dust mite: >0.25 microg/g; cat: >1 microg/g; cockroach: >1 U/g; mouse: >1.6 microg/g. Serious housing code violations were statistically significantly positively associated with dust mite, cat, and mouse allergens (continuous variables), adjusting for mother's income and education, and all neighborhood-level characteristics. In multivariable logistic regression analyses, medium levels of housing code violations were associated with higher dust mite and cat allergens (1.81, 95%CI: 1.08, 3.03 and 3.10, 95%CI: 1.22, 7.92, respectively). A high level of serious housing code violations was associated with higher mouse allergen (2.04, 95%CI: 1.15, 3.62). A medium level of housing code violations was associated with higher cockroach allergen (3.30, 95%CI: 1.11, 9.78). Neighborhood-level characteristics, specifically housing code violations, appear to be related to indoor allergens, which may have implications for future research explorations and policy decisions.

Mouse allergen exposure and decreased risk of allergic rhinitis in school-aged children.

PubMed

Jacobs, Tammy S; Forno, Erick; Brehm, John M; Acosta-Pérez, Edna; Han, Yueh-Ying; Blatter, Joshua; Thorne, Peter; Metwali, Nervana; Colón-Semidey, Angel; Alvarez, María; Canino, Glorisa; Celedón, Juan C

2014-12-01

Little is known about exposure to mouse allergen (Mus m 1) and allergic rhinitis (AR). To evaluate the association between mouse allergen exposure and AR in children. We examined the relation between mouse allergen level in house dust and AR in 511 children aged 6 to 14 years in San Juan, Puerto Rico. Study participants were chosen from randomly selected households using a multistage probability sample design. The study protocol included questionnaires, allergy skin testing, and collection of blood and dust samples. AR was defined as current rhinitis symptoms and skin test reactivity to at least one allergen. In the multivariate analyses, mouse allergen level was associated with a 25% decreased odds of AR in participating children (95% confidence interval, 0.62-0.92). Although endotoxin and mouse allergen levels were significantly correlated (r = 0.184, P < .001), the observed inverse association between Mus m 1 and AR was not explained by levels of endotoxin or other markers of microbial or fungal exposure (peptidoglycan and glucan). Mouse allergen exposure is associated with decreased odds of AR in Puerto Rican school-aged children. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model.

PubMed

Fabian, M Patricia; Stout, Natasha K; Adamkiewicz, Gary; Geggel, Amelia; Ren, Cizao; Sandel, Megan; Levy, Jonathan I

2012-09-18

In the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date. We designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%), which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold. Model design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates. We describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens), medication compliance, seasonality, and medical history on asthma outcomes (symptom-days, medication use, hospitalizations, and emergency room visits). The model can be used to evaluate building interventions and green building construction practices on pollutant concentrations, energy savings, and asthma healthcare utilization costs, and demonstrates the value of a simulation approach for studying complex diseases such as asthma.

The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model

PubMed Central

2012-01-01

Background In the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date. Methods We designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%), which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold. Results Model design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates. Conclusions We describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens), medication compliance, seasonality, and medical history on asthma outcomes (symptom-days, medication use, hospitalizations, and emergency room visits). The model can be used to evaluate building interventions and green building construction practices on pollutant concentrations, energy savings, and asthma healthcare utilization costs, and demonstrates the value of a simulation approach for studying complex diseases such as asthma. PMID:22989068

Sunny hours and variations in the prevalence of asthma in schoolchildren according to the International Study of Asthma and Allergies (ISAAC) Phase III in Spain

NASA Astrophysics Data System (ADS)

Arnedo-Pena, Alberto; García-Marcos, Luis; Fernández-Espinar, Jorge Fuertes; Bercedo-Sanz, Alberto; Aguinaga-Ontoso, Ines; González-Díaz, Carlos; Carvajal-Urueña, Ignacio; Busquet-Monge, Rosa; Suárez-Varela, Maria Morales; de Andoin, Nagore García; Batlles-Garrido, Juan; Blanco-Quirós, Alfredo; Varela, Angel López-Silvarrey; García-Hernández, Gloria

2011-05-01

The objective of this study was to estimate the relationship between the prevalence of asthma in schoolchildren aged 6-7 years and 13-14 years and the mean annual sunny hours (MASH) in Spain, and to explore predictive models for asthma prevalence. The prevalence of asthma was obtained from the International Study of Asthma and Allergies (ISAAC) Phase III 2002-2003, and climate and socio-economic variables from official sources. Nine centres were studied and a further four centres, two of which are in ISAAC, to test the predictive models. Logistic regression was used to estimate adjusted prevalence rates of asthma for each centre, and multiple regression models to study the effects of MASH and other meteorological and socio-economic variables. The adjusted prevalence rate of asthma decreased 0.6% [95% confidence interval (CI) 0.4-0.8%] for the 6-7 years group and 1.1% (95% CI 0.8-1.3%) for the 13-14 years group with an increase in the MASH of 100 h. Relative humidity was negatively associated with asthma in the older age group, and gross province product per capita (GPP) was positively associated with asthma in the younger age group. The predictive models, which included MASH, gender, relative humidity, and GPP, anticipated prevalence rates of asthma without significant differences between the levels observed and those expected in 9 of the11 measurements carried out. The results indicate that sunny hours have a protective effect on the prevalence of asthma in schoolchildren.

Assessing the knowledge to practice gap: The asthma practices of community pharmacists

PubMed Central

Guirguis, Lisa M.

2017-01-01

Background: Community pharmacists are well positioned to identify patients with poorly controlled asthma and trained to optimize asthma therapy. Yet, over 90% of patients with asthma live with uncontrolled disease. We sought to understand the current state of asthma management in practice in Alberta and explore the potential use of the Chat, Check and Chart (CCC) model to enhance pharmacists’ care for patients with asthma. Methods: An 18-question survey was used to examine pharmacists’ monitoring of asthma control and prior use of the CCC tools. Descriptive statistics were used to characterize the response rate, sample demographics, asthma management and CCC use. Survey validity and reliability were established. Results: One hundred randomly selected pharmacists completed the online survey with a 40% (100/250) response rate. A third of responding pharmacists reported talking to most patients about asthma symptoms and medication, with a greater focus on talking with patients on new prescriptions over those with ongoing therapies. Fewer than 1 in 10 pharmacists routinely talked to most patients about asthma action plans (AAPs). The majority of pharmacists (76%) were familiar with the CCC model, and 83% of those reported that the CCC model influenced their practice anywhere from somewhat (45%) to a great deal (38%). Both scales had good reliability, and factor analysis provided support for scale validity. Conclusions: There was considerable variability in pharmacists’ activities in monitoring asthma. Pharmacists rarely used AAPs. The CCC model had a high level of self-reported familiarity, use and influence among pharmacists. PMID:29317938

Using the Health Belief Model to Understand School Nurse Asthma Management

ERIC Educational Resources Information Center

Quaranta, Judith E.; Spencer, Gale A.

2015-01-01

Ten million children in the United States have asthma. Since children are in school about 6 hr a day, school nurses are positioned to intervene and influence asthma outcomes. A descriptive correlational study was designed to investigate performance of school nurses' asthma management behaviors in relationship to asthma knowledge, asthma attitude,…

A Multi-factorial Model for Examining Racial and Ethnic Disparities in Acute Asthma Visits by Children

PubMed Central

Feldman, Jonathan M.; Serebrisky, Denise; Spray, Amanda

2012-01-01

Background Causes of children’s asthma health disparities are complex. Parents’ asthma illness representations may play a role. Purpose The study aims to test a theoretically based, multi-factorial model for ethnic disparities in children’s acute asthma visits through parental illness representations. Methods Structural equation modeling investigated the association of parental asthma illness representations, sociodemographic characteristics, health care provider factors, and social–environmental context with children’s acute asthma visits among 309 White, Puerto Rican, and African American families was conducted. Results Forty-five percent of the variance in illness representations and 30% of the variance in acute visits were accounted for. Statistically significant differences in illness representations were observed by ethnic group. Approximately 30% of the variance in illness representations was explained for whites, 23% for African Americans, and 26% for Puerto Ricans. The model accounted for >30% of the variance in acute visits for African Americans and Puerto Ricans but only 19% for the whites. Conclusion The model provides preliminary support that ethnic heterogeneity in asthma illness representations affects children’s health outcomes. PMID:22160799

Applying the Social Ecological Model to Creating Asthma-Friendly Schools in Louisiana

ERIC Educational Resources Information Center

Nuss, Henry J.; Hester, Laura L.; Perry, Mark A.; Stewart-Briley, Collette; Reagon, Valamar M.; Collins, Pamela

2016-01-01

Background: In 2010, the Louisiana Asthma Management and Prevention Program (LAMP) implemented the Asthma-Friendly Schools Initiative in high-risk Louisiana populations. The social ecological model (SEM) was used as a framework for an asthma program implemented in 70 state K-12 public schools over 2 years. Methods: Activities included a needs…

Micro-imaging of the Mouse Lung via MRI

NASA Astrophysics Data System (ADS)

Wang, Wei

Quantitative measurement of lung microstructure is of great significance in assessment of pulmonary disease, particularly in the earliest stages. Conventional stereological assessment of ex-vivo fixed tissue specimens under the microscope has a long and successful tradition and is regarded as a gold standard, but the invasive nature limits its applications and the practicality of use in longitudinal studies. The technique for diffusion MRI-based 3He lung morphometry was previously developed and validated for human lungs, and was recently extended to ex-vivo mouse lungs. The technique yields accurate, quantitative information about the microstructure and geometry of acinar airways. In this dissertation, the 3He lung morphometry technique is for the first time successfully implemented for in-vivo studies of mice. It can generate spatially-resolved maps of parameters that reveal the microstructure of mouse lung. Results in healthy mice indicate excellent agreement between in-vivo morphometry via 3He MRI and microscopic morphometry after sacrifice. The implementation and validation of 3He morphometry in healthy mice open up new avenues for application of the technique as a precise, noninvasive, in-vivo biomarker of changes in lung microstructure, within various mouse models of lung disease. We have applied 3He morphometry to the Sendai mouse model of lung disease. Specifically, the Sendai-virus model of chronic obstructive lung disease has demonstrated an innate immune response in mouse airways that exhibits similarities to the chronic airway inflammation in human COPD and asthma, but the effect on distal lung parenchyma had not been investigated. We imaged the time course and regional distribution of mouse lung microstructural changes in vivo after Sendai virus (SeV) infection with 1H and 3He diffusion MRI. 1H MR images detected the SeV-induced pulmonary inflammation in vivo and 3He lung morphometry showed modest increase in alveolar duct radius distal to airway inflammation, particularly in the lung periphery, indicating airspace enlargement after virus infection. Another important application of the imaging technique is the study of lung regeneration in a pneumonectomy (PNX) model. Partial resection of the lung by unilateral PNX is a robust model of compensatory lung growth. It is typically studied by postmortem morphometry in which longitudinal assessment in the same animal cannot be achieved. Here we successfully assess the microstructural changes and quantify the compensatory lung growth in vivo in the PNX mouse model via 1H and hyperpolarized 3He diffusion MRI. Our results show complete restoration in lung volume and total alveolar number with enlargement of alveolar size, which is consistent with prior histological studies conducted in different animals at various time points. This dissertation demonstrates that 3He lung morphometry has good sensitivity in quantifying small microstructural changes in the mouse lung and can be applied to a variety of mouse pulmonary models. Particularly, it has great potential to become a valuable tool in understanding the time course and the mechanism of lung growth in individual animals and may provide insight into post-natal lung growth and lung regeneration.

Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen.

PubMed

Gabriele, Lucia; Schiavoni, Giovanna; Mattei, Fabrizio; Sanchez, Massimo; Sestili, Paola; Butteroni, Cinzia; Businaro, Rita; Mirchandani, Ananda; Niedbala, Wanda; Liew, Foo Y; Afferni, Claudia

2013-09-01

Cypress pollen causes respiratory syndromes with different grades of severity, including asthma. IL-33, its receptor ST2, and dendritic cells (DCs) have been implicated in human respiratory allergy. We sought to define a new mouse model of allergy to cypress pollen that recapitulates clinical parameters in allergic patients and to evaluate the implications of DCs and the IL-33/ST2 pathway in this pathology. BALB/c mice, either wild-type or ST2 deficient (ST2(-/-)), were sensitized and challenged with the Cupressus arizonica major allergen nCup a 1. Local and systemic allergic responses were evaluated. Pulmonary cells were characterized by means of flow cytometry. DCs were stimulated with nCup a 1 and tested for their biological response to IL-33 in coculture assays. nCup a 1 causes a respiratory syndrome closely resembling human pollinosis in BALB/c mice. nCup a 1-treated mice exhibit the hallmarks of allergic pathology associated with pulmonary infiltration of eosinophils, T cells, and DCs and a dominant TH2-type immune response. IL-33 levels were increased in lungs and sera of nCup a 1-treated mice and in subjects with cypress allergy. The allergen-specific reaction was markedly reduced in ST2(-/-) mice, which showed fewer infiltrating eosinophils, T cells, and DCs in the lungs. Finally, stimulation of DCs with nCup a 1 resulted in ST2 upregulation that endowed DCs with increased ability to respond to IL-33-mediated differentiation of IL-5- and IL-13-producing CD4 T cells. Our findings define a novel preclinical model of allergy to cypress pollen and provide the first evidence of a functionally relevant linkage between pollen allergens and TH2-polarizing activity by DCs through IL-33/ST2. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The healthy learner model for student chronic condition management--part II: the asthma initiative.

PubMed

Erickson, Cecelia DuPlessis; Splett, Patricia L; Mullett, Sara Stoltzfus; Jensen, Charlotte; Belseth, Stephanie Bisson

2006-12-01

The Healthy Learner Asthma Initiative (HLAI) was designed as a comprehensive, school-community initiative to improve asthma management and produce healthy learners. National asthma guidelines were translated into components of asthma management in the school setting that defined performance expectations and lead to greater quality and consistency of asthma care. The HLAI incorporated evidence-based practice and introduced the role of the asthma resource nurse. Leadership, capacity building, and strong partnerships among school nurses, students, families, and health care providers were essential to the implementation and sustainability of the HLAI. Professional school nursing and evaluation were defined as key requisites to a successful initiative. Evaluation results indicated positive effects on nursing practice, fewer asthma visits to the health office, and better attendance among students who received asthma care in the school health office. The HLAI provided the basis for development of the Healthy Learner Model for Student Chronic Condition Management.

Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma.

PubMed

Wei, Da-Zhen; Guo, Xian-Yang; Lin, Li-Na; Lin, Meng-Xiang; Gong, Yu-Qiang; Ying, Bin-Yu; Huang, Ming-Yuan

2016-12-01

Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.

Validation of the Asthma Illness Representation Scale-Spanish (AIRS-S).

PubMed

Sidora-Arcoleo, Kimberly Joan; Feldman, Jonathan; Serebrisky, Denise; Spray, Amanda

2010-05-01

To expand knowledge surrounding parental illness representations (IRs) of their children's asthma, it is imperative that culturally appropriate survey instruments are developed and validated for use in clinical and research settings. The Asthma Illness Representation Scale (AIRS) provides a structured assessment of the key components of asthma IRs, allowing the health care provider (HCP) to quickly identify areas of discordance with the professional model of asthma management. The English AIRS was developed and validated among a geographically and ethnically diverse sample. The authors present the validation results of the AIRS-S (Spanish) from a sample of Mexican and Puerto Rican parents. The AIRS was translated and back translated per approved methodologies. Factor analysis, internal reliability, external validity, and 2-week test-retest reliability (on a subsample) were carried out and results compared with the validated English version. Data were obtained from 80 Spanish-speaking Mexican and Puerto Rican parents of children with asthma. The sample was recruited from two school-based health centers and a free medical clinic in Phoenix, Arizona, and a hospital-based asthma clinic in Bronx, New York. The original Nature of Asthma Symptoms, Facts About Asthma, and Attitudes Towards Medication Use subscales emerged. Remaining factors were a mixture of items with no coherent or theoretical distinction between them. Interpretation of results is limited due to not meeting the minimum requirement of 5 observations/item. Cronbach's alpha coefficients for the total score (alpha = .77) and majority of subscales (alpha range = .53-.77) were acceptable and consistent with the English version. Parental reports of a positive relationship with the HCP significantly predicted AIRS scores congruent with the professional model; longer asthma duration was associated with beliefs aligned with the lay model; and AIRS scores congruent with the professional model were related to lower asthma severity. Stability in AIRS-S scores over 2 weeks was demonstrated. The AIRS-S is a culturally appropriate instrument that can be used by HCPs to ascertain Spanish-speaking parents' asthma illness beliefs and assess discordance with the professional model of asthma management. This information can be used by the HCP when discussing parent's asthma management strategies for their children during clinical encounters.

The Medical Home Model and Pediatric Asthma Symptom Severity: Evidence from a National Health Survey.

PubMed

Rojanasarot, Sirikan; Carlson, Angeline M

2018-04-01

The objective was to investigate the association between receiving care under the medical home model and parental assessment of the severity of asthma symptoms. It was hypothesized that parents of children who received care under the medical home model reported less severe asthma symptoms compared with their counterparts, whose care did not meet the medical home criteria. Secondary analyses were conducted using cross-sectional data from the 2011-2012 National Survey of Children's Health. Children with asthma aged 0-17 years were included and classified as receiving care from the medical home if their care contained 5 components: a personal doctor, a usual source of sick care, family-centered care, no problems getting referrals, and effective care coordination. Ordinal logistic regression was used to examine the relationship between parent-rated severity of asthma symptoms (mild, moderate, and severe symptoms) and the medical home. Approximately 52% of 8229 children who reported having asthma received care from the medical home. Only 30.8% of children with severe asthma symptoms received care that met the medical home criteria, compared to 55.7% of children with mild symptoms. After accounting for confounding factors, obtaining care under the medical home model decreased the odds of parent-reported severe asthma symptoms by 31% (adjusted odds ratio 0.69; 95% CI, 0.56-0.85). Study results suggest that the medical home model can reduce parent-rated severity of asthma symptoms. The findings highlight the importance of providing medical home care to children with asthma to improve the outcomes that matter most to children and their families.

Review of family relational stress and pediatric asthma: the value of biopsychosocial systemic models.

PubMed

Wood, Beatrice L; Miller, Bruce D; Lehman, Heather K

2015-06-01

Asthma is the most common chronic disease in children. Despite dramatic advances in pharmacological treatments, asthma remains a leading public health problem, especially in socially disadvantaged minority populations. Some experts believe that this health gap is due to the failure to address the impact of stress on the disease. Asthma is a complex disease that is influenced by multilevel factors, but the nature of these factors and their interrelations are not well understood. This paper aims to integrate social, psychological, and biological literatures on relations between family/parental stress and pediatric asthma, and to illustrate the utility of multilevel systemic models for guiding treatment and stimulating future research. We used electronic database searches and conducted an integrated analysis of selected epidemiological, longitudinal, and empirical studies. Evidence is substantial for the effects of family/parental stress on asthma mediated by both disease management and psychobiological stress pathways. However, integrative models containing specific pathways are scarce. We present two multilevel models, with supporting data, as potential prototypes for other such models. We conclude that these multilevel systems models may be of substantial heuristic value in organizing investigations of, and clinical approaches to, the complex social-biological aspects of family stress in pediatric asthma. However, additional systemic models are needed, and the models presented herein could serve as prototypes for model development. © 2015 Family Process Institute.

Development of an International School Nurse Asthma Care Coordination Model

PubMed Central

Garwick, Ann W.; Svavarsdóttir, Erla Kolbrun; Seppelt, Ann M.; Looman, Wendy S.; Anderson, Lori S.; Örlygsdóttir, Brynja

2015-01-01

Aim To identify and compare how school nurses in Reykjavik, Iceland and St. Paul, Minnesota coordinated care for youth with asthma (ages 10–18) and to develop an asthma school nurse care coordination model. Background Little is known about how school nurses coordinate care for youth with asthma in different countries. Design A qualitative descriptive study design using focus group data. Methods Six focus groups with 32 school nurses were conducted in Reykjavik (n=17) and St. Paul (n=15) using the same protocol between September 2008 – January 2009. Descriptive content analytic and constant comparison strategies were used to categorize and compare how school nurses coordinated care, which resulted in the development of an International School Nurse Asthma Care Coordination Model. Findings Participants in both countries spontaneously described a similar asthma care coordination process that involved information gathering, assessing risk for asthma episodes, prioritizing health care needs and anticipating and planning for student needs at the individual and school levels. This process informed how they individualized symptom management, case management and/or asthma education. School nurses played a pivotal part in collaborating with families, school and health care professionals to ensure quality care for youth with asthma. Conclusions Results indicate a high level of complexity in school nurses’ approaches to asthma care coordination that were responsive to the diverse and changing needs of students in school settings. The conceptual model derived provides a framework for investigators to use in examining the asthma care coordination process of school nurses in other geographic locations. PMID:25223389

Patients' expectations of asthma treatment.

PubMed

Mancuso, Carol A; Rincon, Melina; Robbins, Laura; Charlson, Mary E

2003-12-01

A multicomponent model has been developed to explain patients' unmet expectations of medical care. The model proposes that expectations are related to patients' personal experiences with illness, perceived vulnerability to disease, transmitted knowledge, and perceived severity of disease. The objective of this cross-sectional study was to determine whether this model can be applied to patients' unrealistic expectations of treatment outcomes, specifically expecting to be cured of asthma. In total, 230 patients observed in a primary care practice in New York City were interviewed in person with open-ended questions about their expectations of asthma treatment. Responses were analyzed with qualitative techniques to generate categories of expectations. Patients had a mean age of 41 +/- 11 years, 21% were white, 30% African American, 42% Latino, and 7% other groups. Major categories of expectations were generated from patients' responses and included symptom relief (expected by 52%), cure (36%), improved physical function (21%), and improved psychological well-being (15%). The category of expecting a cure was assessed with patients' responses to the following items representing components of the model: 1) resource utilization and medication requirements for asthma (representing severity of disease); 2) perceived quality of asthma care and satisfaction with care (representing past asthma experiences); 3) the Asthma Self-Efficacy Scale (representing perceived vulnerability to exacerbations); and 4) experiences of social network contacts with asthma and the Check Your Asthma IQ survey (representing transmitted knowledge). In bivariate analysis, patients who expected a cure were more likely to be Latino or Native American or Asian (p = 0.02), to have never required oral corticosteroids (p = 0.004), to be dissatisfied with the status of their asthma (p = 0.008), to know others who were limited by asthma (p = 0.03), to have worse Asthma Self-Efficacy Scale scores (p = 0.002), to have worse Check Your Asthma IQ scores (p = 0.04), and to currently be taking inhaled corticosteroids (p = 0.03). In multivariate analysis, worse asthma self-efficacy (p = 0.008), never having required oral corticosteroids (p = 0.005), and currently taking inhaled corticosteroids (p = 0.05) remained associated with expecting a cure. As a result of this study, we found that patients have multiple expectations of asthma treatment, including realistic expectations such as symptom relief and improved function, as well as unrealistic expectations, specifically to be cured of asthma. A multicomponent model of patient and disease characteristics was associated with this unrealistic expectation. These findings indicate that clinicians can intervene in diverse areas to foster realistic expectations of treatment outcomes among asthma patients.

Comparative evaluation of two asthma care quality measures among Medicaid beneficiaries.

PubMed

Samnaliev, Mihail; Baxter, Jeffrey D; Clark, Robin E

2009-05-01

The relative performance of asthma care quality measures has not been evaluated in Medicaid populations. Using complete claims and pharmaceutical data for 19,076 patients with persistent asthma (based on Health Effectiveness and Data Information Set criteria) in five Medicaid populations, we compared the following two measures of asthma care quality: filling prescriptions for controller asthma medications within 1 year and the ratio of controller medication to the total number of asthma medication prescriptions filled within 1 year. We calculated whether meeting each quality measure was associated with decreased odds of emergency department (ED) treatment episodes. We then compared the odds ratios, receiver operating characteristic (ROC) curves, and deviances between models, using each measure to predict ED utilization in Medicaid populations. Although meeting each measure was associated with lower odds of ED utilization, this decrease was larger if the controller asthma medication measure was met rather than the ratio measure. Additionally, models using the controller medication measure had greater areas under the ROC curve and smaller deviances than models using the ratio measure. Both administrative measures of asthma care quality were associated with lower odds of ED utilization. The controller medication measure of asthma care quality may be better than the ratio measure in relation to emergency asthma care utilization by Medicaid beneficiaries.

Forecasting asthma-related hospital admissions in London using negative binomial models.

PubMed

Soyiri, Ireneous N; Reidpath, Daniel D; Sarran, Christophe

2013-05-01

Health forecasting can improve health service provision and individual patient outcomes. Environmental factors are known to impact chronic respiratory conditions such as asthma, but little is known about the extent to which these factors can be used for forecasting. Using weather, air quality and hospital asthma admissions, in London (2005-2006), two related negative binomial models were developed and compared with a naive seasonal model. In the first approach, predictive forecasting models were fitted with 7-day averages of each potential predictor, and then a subsequent multivariable model is constructed. In the second strategy, an exhaustive search of the best fitting models between possible combinations of lags (0-14 days) of all the environmental effects on asthma admission was conducted. Three models were considered: a base model (seasonal effects), contrasted with a 7-day average model and a selected lags model (weather and air quality effects). Season is the best predictor of asthma admissions. The 7-day average and seasonal models were trivial to implement. The selected lags model was computationally intensive, but of no real value over much more easily implemented models. Seasonal factors can predict daily hospital asthma admissions in London, and there is a little evidence that additional weather and air quality information would add to forecast accuracy.

Improved Guideline Adherence With Integrated Sickle Cell Disease and Asthma Care.

PubMed

McClain, Brandi L; Ivy, Zalaya K; Bryant, Valencia; Rodeghier, Mark; DeBaun, Michael R

2016-07-01

In children with sickle cell disease (SCD), concomitant asthma is associated with increased morbidity and mortality when compared with children with SCD without asthma. Despite the well-established burden of asthma in children with SCD, no paradigm of care exists for the co-management of these two diseases. To address this gap, an integrated SCD and asthma clinic was created in a community health center that included (1) a dual respiratory therapist/asthma case manager; (2) an SCD nurse practitioner with asthma educator certification; (3) an onsite pulmonary function test laboratory; (4) a pediatric hematologist with expertise in managing SCD and asthma; and (5) application of the National Asthma Education and Prevention Program guidelines. A before (2010-2012) and after (2013-2014) study design was used to assess for improved quality of care with implementation of an integrative care model among 61 children with SCD and asthma followed from 2010 to 2014. Asthma action plan utilization after initial diagnosis increased with the integrative care model (n=16, 56% before, 100% after, p=0.003), as did the use of spirometry in children aged ≥5 years (n=41, 65% before, 95% after, p<0.001) and correction of lower airway obstruction (n=10, 30% before, 80% after, p=0.03). Although the use of an integrative care model for SCD and asthma improved evidence-based asthma care, longer follow-up and evaluation will be needed to determine the impact on SCD-related morbidity. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice

PubMed Central

Oriss, Timothy B.; Raundhal, Mahesh; Morse, Christina; Huff, Rachael E.; Das, Sudipta; Hannum, Rachel; Gauthier, Marc C.; Scholl, Kathryn L.; Chakraborty, Krishnendu; Nouraie, Seyed M.; Wenzel, Sally E.; Ray, Prabir

2017-01-01

Severe asthma (SA) is a significant problem both clinically and economically, given its poor response to corticosteroids (CS). We recently reported a complex type 1–dominated (IFN-γ–dominated) immune response in more than 50% of severe asthmatics despite high-dose CS treatment. Also, IFN-γ was found to be critical for increased airway hyperreactivity (AHR) in our model of SA. The transcription factor IRF5 expressed in M1 macrophages can induce a Th1/Th17 response in cocultured human T cells. Here we show markedly higher expression of IRF5 in bronchoalveolar lavage (BAL) cells of severe asthmatics as compared with that in cells from milder asthmatics or healthy controls. Using our SA mouse model, we demonstrate that lack of IRF5 in lymph node migratory DCs severely limits their ability to stimulate the generation of IFN-γ– and IL-17–producing CD4+ T cells and IRF5–/– mice subjected to the SA model displayed significantly lower IFN-γ and IL-17 responses, albeit showing a reciprocal increase in Th2 response. However, the absence of IRF5 rendered the mice responsive to CS with suppression of the heightened Th2 response. These data support the notion that IRF5 inhibition in combination with CS may be a viable approach to manage disease in a subset of severe asthmatics. PMID:28515358

Glycyrrhizin and Long-Term Histopathologic Changes in a Murine Model of Asthma

PubMed Central

Hocaoglu, Arzu Babayigit; Karaman, Ozkan; Erge, Duygu Olmez; Erbil, Guven; Yilmaz, Osman; Bagriyanik, Alper; Uzuner, Nevin

2011-01-01

Background Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. Objective In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. Methods Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. Results As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) μm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) μm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 μm2; and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 μm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers (P < 0.001 for all) in the asthma group compared with in the control group. The number of goblet (P < 0.001) and mast (P < 0.02) cells and the thickness of basement membrane (P < 0.001), subepithelial smooth muscle layers (P ≤ 0.001), and epithelium of the lung (P < 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was no statistically significant difference between the 2 groups in the histopathologic parameters, including thickness of basement membrane (P = 0.514), subepithelial smooth muscle (P = 0.054), and epithelium (P = 1.0) and number of mast (P = 0.075) and goblet (P = 0.988) cells. Conclusions The results of this study suggest that the group receiving glycyrrhizin had amelioration of all established chronic histopathologic changes of lung in the mouse model of asthma. Further studies are needed to evaluate the efficacy of glycyrrhizin in the management of asthma. PMID:24648593

Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

PubMed

de Castro, Ligia Lins; Xisto, Debora Gonçalves; Kitoko, Jamil Zola; Cruz, Fernanda Ferreira; Olsen, Priscilla Christina; Redondo, Patricia Albuquerque Garcia; Ferreira, Tatiana Paula Teixeira; Weiss, Daniel Jay; Martins, Marco Aurélio; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

2017-06-24

Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 10 5 human AD-MSCs, or EVs (released by 10 5  AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3 + CD4 + T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3 + CD4 + T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3 + CD4 + T cells in the mediastinal lymph nodes. In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different mechanisms of action of AD-MSCs versus their EVs.

Greater involvement of neurokinins found in Guinea pig models of severe asthma compared with mild asthma.

PubMed

Mukaiyama, Osamu; Morimoto, Kiyoshi; Nosaka, Emi; Takahashi, Sakiko; Yamashita, Makoto

2004-08-01

Involvement of neurokinins in asthma has been previously pointed out by several reports. However, the relationship between neurokinins and the severity of asthma has remained unclear. We developed a model of mild asthma (model I) and severe asthma (model II) in guinea pigs, and investigated the function of neurokinins in both models. In models I and II, systemically sensitized guinea pigs were made to inhale ovalbumin once and three times, respectively. Substance P (SP) and neurokinin A (NKA) concentrations in the bronchoalveolar lavage fluid (BALF) were measured in models I and II. Then, the effects of a capsaicin pretreatment, which depletes neurokinins, in both animal models on airway narrowing induced by the last ovalbumin inhalation, airway hyperresponsiveness to inhaled methacholine, and eosinophil accumulation in BALF, were investigated. SP concentration tended to increase and the NKA concentration increased significantly in model II, but not in model I. Capsaicin pretreatment significantly inhibited the late bronchial response that was observed 2-6 h after the last ovalbumin inhalation, airway hyperresponsiveness and eosinophil accumulation in model II. On the other hand, it had no effects on the responses in model I. It is suggested that the more severe the disease, the greater the involvement of neurokinins. Copyright 2004 S. Karger AG, Basel

Mechanisms of anaphylaxis in human low-affinity IgG receptor locus knock-in mice.

PubMed

Gillis, Caitlin M; Jönsson, Friederike; Mancardi, David A; Tu, Naxin; Beutier, Héloïse; Van Rooijen, Nico; Macdonald, Lynn E; Murphy, Andrew J; Bruhns, Pierre

2017-04-01

Anaphylaxis can proceed through distinct IgE- or IgG-dependent pathways, which have been investigated in various mouse models. We developed a novel mouse strain in which the human low-affinity IgG receptor locus, comprising both activating (hFcγRIIA, hFcγRIIIA, and hFcγRIIIB) and inhibitory (hFcγRIIB) hFcγR genes, has been inserted into the equivalent murine locus, corresponding to a locus swap. We sought to determine the capabilities of hFcγRs to induce systemic anaphylaxis and identify the cell types and mediators involved. hFcγR expression on mouse and human cells was compared to validate the model. Passive systemic anaphylaxis was induced by injection of heat-aggregated human intravenous immunoglobulin and active systemic anaphylaxis after immunization and challenge. Anaphylaxis severity was evaluated based on hypothermia and mortality. The contribution of receptors, mediators, or cell types was assessed based on receptor blockade or depletion. The human-to-mouse low-affinity FcγR locus swap engendered hFcγRIIA/IIB/IIIA/IIIB expression in mice comparable with that seen in human subjects. Knock-in mice were susceptible to passive and active anaphylaxis, accompanied by downregulation of both activating and inhibitory hFcγR expression on specific myeloid cells. The contribution of hFcγRIIA was predominant. Depletion of neutrophils protected against hypothermia and mortality. Basophils contributed to a lesser extent. Anaphylaxis was inhibited by platelet-activating factor receptor or histamine receptor 1 blockade. Low-affinity FcγR locus-switched mice represent an unprecedented model of cognate hFcγR expression. Importantly, IgG-related anaphylaxis proceeds within a native context of activating and inhibitory hFcγRs, indicating that, despite robust hFcγRIIB expression, activating signals can dominate to initiate a severe anaphylactic reaction. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Healthy Learner Model for Student Chronic Condition Management--Part II: The Asthma Initiative

ERIC Educational Resources Information Center

Erickson, Cecelia DuPlessis; Splett, Patricia L.; Mullett, Sara Stoltzfus; Jensen, Charlotte; Belseth, Stephanie Bisson

2006-01-01

The Healthy Learner Asthma Initiative (HLAI) was designed as a comprehensive, school-community initiative to improve asthma management and produce healthy learners. National asthma guidelines were translated into components of asthma management in the school setting that defined performance expectations and lead to greater quality and consistency…

Treating asthma with a self-management model of illness behaviour in an Australian community pharmacy setting.

PubMed

Smith, Lorraine; Bosnic-Anticevich, Sinthia Z; Mitchell, Bernadette; Saini, Bandana; Krass, Ines; Armour, Carol

2007-04-01

Asthma affects a considerable proportion of the population worldwide and presents a significant health problem in Australia. Given its chronic nature, effective asthma self-management approaches are important. However, despite research and interventions targeting its treatment, the management of asthma remains problematic. This study aimed to develop, from a theoretical basis, an asthma self-management model and implement it in an Australian community pharmacy setting in metropolitan Sydney, using a controlled, parallel-groups repeated-measures design. Trained pharmacists delivered a structured, step-wise, patient-focused asthma self-management program to adult participants over a 9-month period focusing on identification of asthma problems, goal setting and strategy development. Data on process- clinical- and psychosocial-outcome measures were gathered. Results showed that participants set an average of four new goals and six repeated goals over the course of the intervention. Most common goal-related themes included asthma triggers, asthma control and medications. An average of nine strategies per participant was developed to achieve the set goals. Common strategies involved visiting a medical practitioner for review of medications, improving adherence to medications and using medications before exercise. Clinical and psychosocial outcomes indicated significant improvements over time in asthma symptom control, asthma-related self-efficacy and quality of life, and negative affect. These results suggest that an asthma self-management model of illness behaviour has the potential to provide patients with a range of process skills for self-management, and deliver improvements in clinical and psychosocial indicators of asthma control. The results also indicate the capacity for the effective delivery of such an intervention by pharmacists in Australian community pharmacy settings.

Fluctuations in air pollution give risk warning signals of asthma hospitalization

NASA Astrophysics Data System (ADS)

Hsieh, Nan-Hung; Liao, Chung-Min

2013-08-01

Recent studies have implicated that air pollution has been associated with asthma exacerbations. However, the key link between specific air pollutant and the consequent impact on asthma has not been shown. The purpose of this study was to quantify the fluctuations in air pollution time-series dynamics to correlate the relationships between statistical indicators and age-specific asthma hospital admissions. An indicators-based regression model was developed to predict the time-trend of asthma hospital admissions in Taiwan in the period 1998-2010. Five major pollutants such as particulate matters with aerodynamic diameter less than 10 μm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) were included. We used Spearman's rank correlation to detect the relationships between time-series based statistical indicators of standard deviation, coefficient of variation, skewness, and kurtosis and monthly asthma hospitalization. We further used the indicators-guided Poisson regression model to test and predict the impact of target air pollutants on asthma incidence. Here we showed that standard deviation of PM10 data was the most correlated indicators for asthma hospitalization for all age groups, particularly for elderly. The skewness of O3 data gives the highest correlation to adult asthmatics. The proposed regression model shows a better predictability in annual asthma hospitalization trends for pediatrics. Our results suggest that a set of statistical indicators inferred from time-series information of major air pollutants can provide advance risk warning signals in complex air pollution-asthma systems and aid in asthma management that depends heavily on monitoring the dynamics of asthma incidence and environmental stimuli.

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds

PubMed Central

Jarvis, J; Seed, M; Elton, R; Sawyer, L; Agius, R

2005-01-01

Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard. PMID:15778257

Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge.

PubMed

Kelada, Samir N P

2016-09-08

Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene-environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design in which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics. Copyright © 2016 Kelada.

Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

DOE PAGES

Kelada, Samir N. P.

2016-07-22

Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene–environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design inmore » which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics.« less

Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelada, Samir N. P.

Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene–environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design inmore » which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics.« less

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus.

PubMed

Samarasinghe, Amali E; Melo, Rossana C N; Duan, Susu; LeMessurier, Kim S; Liedmann, Swantje; Surman, Sherri L; Lee, James J; Hurwitz, Julia L; Thomas, Paul G; McCullers, Jonathan A

2017-04-15

Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus-infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8 + T cell numbers in the airways. In vitro assays with primary or bone marrow-derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide-exposed eosinophils induced CD8 + T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. Copyright © 2017 by The American Association of Immunologists, Inc.

Budesonide suppresses pulmonary antibacterial host defense by down-regulating cathelicidin-related antimicrobial peptide in allergic inflammation mice and in lung epithelial cells

PubMed Central

2013-01-01

Background Glucocorticoids are widely regarded as the most effective treatment for asthma. However, the direct impact of glucocorticoids on the innate immune system and antibacterial host defense during asthma remain unclear. Understanding the mechanisms underlying this process is critical to the clinical application of glucocorticoids for asthma therapy. After sensitization and challenge with ovalbumin (OVA), BALB/c mice were treated with inhaled budesonide and infected with Pseudomonas aeruginosa (P. aeruginosa). The number of viable bacteria in enflamed lungs was evaluated, and levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum were measured. A lung epithelial cell line was pretreated with budesonide. Levels of cathelicidin-related antimicrobial peptide (CRAMP) were measured by immunohistochemistry and western blot analysis. Intracellular bacteria were observed in lung epithelial cells. Results Inhaled budesonide enhanced lung infection in allergic mice exposed to P. aeruginosa and increased the number of viable bacteria in lung tissue. Higher levels of IL-4 and lower levels of IFN-γ were observed in the serum. Budesonide decreased the expression of CRAMP, increased the number of internalized P. aeruginosa in OVA-challenged mice and in lung epithelial cell lines. These data indicate that inhaled budesonide can suppress pulmonary antibacterial host defense by down-regulating CRAMP in allergic inflammation mice and in cells in vitro. Conclusions Inhaled budesonide suppressed pulmonary antibacterial host defense in an asthmatic mouse model and in lung epithelium cells in vitro. This effect was dependent on the down-regulation of CRAMP. PMID:23387852

Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

PubMed

Sun, F J; Zou, L Y; Tong, D M; Lu, X Y; Li, J; Deng, C B

2017-08-31

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

Asthma control and productivity loss in those with work-related asthma: A population-based study.

PubMed

Wong, Alyson; Tavakoli, Hamid; Sadatsafavi, Mohsen; Carlsten, Chris; FitzGerald, J Mark

2017-06-01

In Canada, asthma is the third leading cause of work loss, yet little is known about the associated productivity loss. The goal of this study was to look at the relationship between asthma control and productivity loss, particularly contrasting those with work-related asthma (WRA) and non-work-related asthma (NWRA). A population-based random sample of adults with asthma in British Columbia, Canada, was prospectively recruited. Asthma control was graded according to Global Initiative for Asthma classification, while productivity loss and presence of WRA was assessed using questionnaires. Ordinal regression models were then used to associate WRA with asthma control. Generalized linear models were applied to estimate the average productivity loss associated with different levels of asthma control among those with WRA and NWRA. The study included 300 employed adults. Sixty (20%) had WRA. The odds of being controlled were significantly lower in those with WRA (OR = 0.23, 95% CI: 0.09, 0.56; P < 0.01). Those with WRA and uncontrolled asthma had a significant difference in productivity loss due to presenteeism ($659.1 [95% CI: 12.9, 1581.5; P = 0.04]), but not absenteeism ($88.7 [95% CI: -86.5, 279.6; P = 0.35]), when compared to those with NWRA and uncontrolled asthma. There was no significant difference when a similar comparison was made for those with controlled or partially controlled asthma. WRA is associated with worse asthma control and increased productivity loss. Presenteeism makes a significant contribution to productivity loss and should be considered when evaluating the overall economic burden of asthma, particularly WRA.

Development of an asthma disease management program in a children's hospital.

PubMed

Miller, Kelly; Ward-Smith, Peggy; Cox, Karen; Jones, Erika M; Portnoy, Jay M

2003-11-01

The incidence, morbidity, and mortality of asthma have been increasing at an alarming rate, making asthma the most common chronic illness of childhood. An asthma disease management program was developed to improve the care and management of patients with asthma--a comprehensive health care delivery model that was designed to improve the management of patients with asthma was designed and implemented. The goal of the program was to provide high-quality interventions for those children diagnosed with asthma. The asthma disease management program at Children's Mercy Hospital improved the care received, decreased costs, and improved the quality of life for those children with asthma.

A twin study of early-childhood asthma in Puerto Ricans.

PubMed

Bunyavanich, Supinda; Silberg, Judy L; Lasky-Su, Jessica; Gillespie, Nathan A; Lange, Nancy E; Canino, Glorisa; Celedón, Juan C

2013-01-01

The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood. To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤ 3 years old. 678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages 1 and 3 years: physician-diagnosed asthma, asthma medication use in the past year, and ≥ 1 hospitalization for asthma in the past year. Models were additionally adjusted for early-life environmental tobacco smoke exposure, sex, and age. The prevalences of physician-diagnosed asthma, asthma medication use, and hospitalization for asthma were 11.6%, 10.8%, 4.9% at age 1 year, and 34.1%, 40.1%, and 8.5% at 3 years, respectively. Shared environmental effects contributed to the majority of variance in susceptibility to physician-diagnosed asthma and asthma medication use in the first year of life (84%-86%), while genetic effects drove variance in all phenotypes (45%-65%) at age 3 years. Early-life environmental tobacco smoke, sex, and age contributed to variance in susceptibility. Our longitudinal study in Puerto Rican twins demonstrates a changing contribution of shared environmental effects to liability for physician-diagnosed asthma and asthma medication use between ages 1 and 3 years. Early-life environmental tobacco smoke reduction could markedly reduce asthma morbidity in young Puerto Rican children.

Genetically manipulated mouse models of lung disease: potential and pitfalls

PubMed Central

Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

2012-01-01

Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

Full-chain health impact assessment of traffic-related air pollution and childhood asthma.

PubMed

Khreis, Haneen; de Hoogh, Kees; Nieuwenhuijsen, Mark J

2018-05-01

Asthma is the most common chronic disease in children. Traffic-related air pollution (TRAP) may be an important exposure contributing to its development. In the UK, Bradford is a deprived city suffering from childhood asthma rates higher than national and regional averages and TRAP is of particular concern to the local communities. We estimated the burden of childhood asthma attributable to air pollution and specifically TRAP in Bradford. Air pollution exposures were estimated using a newly developed full-chain exposure assessment model and an existing land-use regression model (LUR). We estimated childhood population exposure to NO x and, by conversion, NO 2 at the smallest census area level using a newly developed full-chain model knitting together distinct traffic (SATURN), vehicle emission (COPERT) and atmospheric dispersion (ADMS-Urban) models. We compared these estimates with measurements and estimates from ESCAPE's LUR model. Using the UK incidence rate for childhood asthma, meta-analytical exposure-response functions, and estimates from the two exposure models, we estimated annual number of asthma cases attributable to NO 2 and NO x in Bradford, and annual number of asthma cases specifically attributable to traffic. The annual average census tract levels of NO 2 and NO x estimated using the full-chain model were 15.41 and 25.68 μg/m 3 , respectively. On average, 2.75 μg/m 3 NO 2 and 4.59 μg/m 3 NO x were specifically contributed by traffic, without minor roads and cold starts. The annual average census tract levels of NO 2 and NO x estimated using the LUR model were 21.93 and 35.60 μg/m 3 , respectively. The results indicated that up to 687 (or 38% of all) annual childhood asthma cases in Bradford may be attributable to air pollution. Up to 109 cases (6%) and 219 cases (12%) may be specifically attributable to TRAP, with and without minor roads and cold starts, respectively. This is the first study undertaking full-chain health impact assessment of TRAP and childhood asthma in a disadvantaged population with public concern about TRAP. It further adds to scarce literature exploring the impact of different exposure assessments. In conservative estimates, air pollution and TRAP are estimated to cause a large, but largely preventable, childhood asthma burden. Future progress with childhood asthma requires a move beyond the prevalent disease control-based approach toward asthma prevention. Copyright © 2018 Elsevier Ltd. All rights reserved.

Long-Acting Beta Agonists Enhance Allergic Airway Disease.

PubMed

Knight, John M; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A; Milner, Joshua D; Zhang, Yuan; Mandal, Pijus K; Luong, Amber; Kheradmand, Farrah; McMurray, John S; Corry, David B

2015-01-01

Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.

Dietary patterns and asthma prevalence, incidence and control.

PubMed

Barros, R; Moreira, A; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Lopes, C; Severo, M; Moreira, P

2015-11-01

The increased asthma prevalence in westernized societies has been suggested to be related to environment exposures and lifestyle changes, particularly diet. We aimed to explore the association between dietary patterns and asthma prevalence, incidence and control in a nationally representative population. Data from 32,644 adults, 53% female, from the 4th Portuguese National Health Survey were analysed. Prevalence of asthma was 5.3%; 'current asthma', defined by asthma symptoms within previous year, 3.5%; 'current medicated asthma' defined by use of asthma medication within previous year, 3.0%; 'current severe asthma' defined by emergency visit because of asthma within previous year, 1.4%; and 'incident asthma', 0.2%. Dietary patterns (DP) were identified by latent trait models based on dietary intake. Unconditional logistic regression models were performed to analyse association between DP and asthma. Age, gender, education, family income, proxy reporting information, smoking, body mass index and physical activity level were analysed as confounders. Two of the five identified DP were associated with asthma: 'high fat, sugar and salt' DP (positively correlated with pastry, chocolate and sweet desserts, candies, salty snacks, chips, fruit juices, soft drinks and alcoholic beverages consumption at snacks) was associated with asthma prevalence (OR = 1.13, 95% CI = 1.03, 1.24) and current severe asthma (OR = 1.23, 95% CI = 1.03, 1.48), while 'fish, fruit and vegetables' DP (positively correlated with fish, vegetables and fruit intake at meals) was negatively associated with current (OR = 0.84, 95% CI = 0.73, 0.98), and current medicated asthma (OR = 0.84, 95% CI = 0.72, 0.98), after adjustment for confounders. Our results suggest a protective association between 'fish, vegetables and fruit' DP and current asthma and current medicated asthma, and a detrimental association between 'high fat, sugar and salt' DP and severe asthma prevalence, further supporting the rational for diet and lifestyle intervention studies in asthma based on whole dietary patterns and physical activity. © 2015 John Wiley & Sons Ltd.

Forecasting peak asthma admissions in London: an application of quantile regression models.

PubMed

Soyiri, Ireneous N; Reidpath, Daniel D; Sarran, Christophe

2013-07-01

Asthma is a chronic condition of great public health concern globally. The associated morbidity, mortality and healthcare utilisation place an enormous burden on healthcare infrastructure and services. This study demonstrates a multistage quantile regression approach to predicting excess demand for health care services in the form of asthma daily admissions in London, using retrospective data from the Hospital Episode Statistics, weather and air quality. Trivariate quantile regression models (QRM) of asthma daily admissions were fitted to a 14-day range of lags of environmental factors, accounting for seasonality in a hold-in sample of the data. Representative lags were pooled to form multivariate predictive models, selected through a systematic backward stepwise reduction approach. Models were cross-validated using a hold-out sample of the data, and their respective root mean square error measures, sensitivity, specificity and predictive values compared. Two of the predictive models were able to detect extreme number of daily asthma admissions at sensitivity levels of 76 % and 62 %, as well as specificities of 66 % and 76 %. Their positive predictive values were slightly higher for the hold-out sample (29 % and 28 %) than for the hold-in model development sample (16 % and 18 %). QRMs can be used in multistage to select suitable variables to forecast extreme asthma events. The associations between asthma and environmental factors, including temperature, ozone and carbon monoxide can be exploited in predicting future events using QRMs.

Forecasting peak asthma admissions in London: an application of quantile regression models

NASA Astrophysics Data System (ADS)

Soyiri, Ireneous N.; Reidpath, Daniel D.; Sarran, Christophe

2013-07-01

Asthma is a chronic condition of great public health concern globally. The associated morbidity, mortality and healthcare utilisation place an enormous burden on healthcare infrastructure and services. This study demonstrates a multistage quantile regression approach to predicting excess demand for health care services in the form of asthma daily admissions in London, using retrospective data from the Hospital Episode Statistics, weather and air quality. Trivariate quantile regression models (QRM) of asthma daily admissions were fitted to a 14-day range of lags of environmental factors, accounting for seasonality in a hold-in sample of the data. Representative lags were pooled to form multivariate predictive models, selected through a systematic backward stepwise reduction approach. Models were cross-validated using a hold-out sample of the data, and their respective root mean square error measures, sensitivity, specificity and predictive values compared. Two of the predictive models were able to detect extreme number of daily asthma admissions at sensitivity levels of 76 % and 62 %, as well as specificities of 66 % and 76 %. Their positive predictive values were slightly higher for the hold-out sample (29 % and 28 %) than for the hold-in model development sample (16 % and 18 %). QRMs can be used in multistage to select suitable variables to forecast extreme asthma events. The associations between asthma and environmental factors, including temperature, ozone and carbon monoxide can be exploited in predicting future events using QRMs.

Risk Factors in Preschool Children for Predicting Asthma During the Preschool Age and the Early School Age: a Systematic Review and Meta-Analysis.

PubMed

Bao, Yixia; Chen, Zhimin; Liu, Enmei; Xiang, Li; Zhao, Deyu; Hong, Jianguo

2017-11-18

The aim of this study was to identify risk factors of asthma among children < 6 years old (preschool age) for predicting asthma during the preschool age and early school age (≤ 10 years of age). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017. Prospective or retrospective cohort and case-control studies were included. Studies had to have evaluated risk factors or a predictive model for developing asthma in children ≤ 6 years of age or persistent asthma in early school age. A total of 17 studies were included in the analysis. Factors associated with developing asthma in children ≤ 10 years of age (both pre-school and early school age) included male gender (pooled OR = 1.70, P < 0.001), atopic dermatitis (pooled OR = 2.02, P < 0.001), a family history of asthma (pooled OR = 2.20, P < 0.001), and serum IgE levels ≥ 60 kU/l or having specific IgE (pooled OR = 2.36, P < 0.001). A history of exposure to smoke or wheezing was also associated with persistent asthma in early school age (pooled OR = 1.51, P = 0.030 and pooled OR = 2.59, P < 0.001, respectively). In general, asthma predictive models (e.g., API, PIAMA, PAPS) had relatively low sensitivity (range, 21% to 71.4%) but high specificity (range, 69% to 98%). The study found that male gender, exposure to smoke, atopic dermatitis, family history of asthma, history of wheezing, and serum IgE level ≥ 60 kU/l or having specific IgE were significantly associated with developing asthma by either preschool or early school age. Asthma predictive models can be developed by those risk factors.

A Multiomics Approach to Identify Genes Associated with Childhood Asthma Risk and Morbidity.

PubMed

Forno, Erick; Wang, Ting; Yan, Qi; Brehm, John; Acosta-Perez, Edna; Colon-Semidey, Angel; Alvarez, Maria; Boutaoui, Nadia; Cloutier, Michelle M; Alcorn, John F; Canino, Glorisa; Chen, Wei; Celedón, Juan C

2017-10-01

Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.

An evaluation of a community pharmacy-based rural asthma management service.

PubMed

Saini, Bandana; Filipovska, Julija; Bosnic-Anticevich, Sinthia; Taylor, Susan; Krass, Ines; Armour, Carol

2008-04-01

To compare the effect of a pharmacist-delivered rural asthma management service (RAMS) on health outcomes for people with asthma in a rural/regional area with 'standard care' delivered through community pharmacies. A parallel group controlled repeated measures study. Community pharmacies in Central West New South Wales. Standardised protocols and resources based on national asthma management guidelines, delivered by specially trained community pharmacists. Patients visited the pharmacy at baseline and 1, 3 and 6 months after baseline in the intervention group and at baseline plus 6 months after baseline in the control group. The intervention pharmacists (n = 12) were trained to deliver the RAMS model, while control pharmacists (n = 8) provided standard asthma care to their recruited patients. Fifty-one and 39 patients were recruited by intervention and control pharmacists. Asthma severity score which was a composite score based on recency, frequency and severity of asthma symptoms, and asthma history. Data compared at the final visit between groups indicated that the RAMS patient group demonstrated a significant reduction in the asthma severity scores (7.9 +/- 2.6 versus 10.4 +/- 2.6, P < 0.001); a reduction in the risk of non-adherence to medication scores (1.6 +/- 0.7 versus 2.3 +/- 1.1, P < 0.001); and an increase in the proportion of patients owning a written action plan (50% versus 23%, P = 0.04). These results indicated that the community pharmacy-based RAMS model can improve asthma outcomes for patients in rural settings, and similar models for asthma and other chronic diseases should be tested rigorously and adopted in rural primary care practice.

Childhood incident asthma and traffic-related air pollution at home and school.

PubMed

McConnell, Rob; Islam, Talat; Shankardass, Ketan; Jerrett, Michael; Lurmann, Fred; Gilliland, Frank; Gauderman, Jim; Avol, Ed; Künzli, Nino; Yao, Ling; Peters, John; Berhane, Kiros

2010-07-01

Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma. We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children's Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO(2)), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric. Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25-1.82] and near schools (HR 1.45; 95% CI, 1.06-1.98). Ambient NO(2) measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18-4.01). In models with both NO(2) and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO(2) was attenuated (HR 1.37; 95% CI, 0.69-2.71). Traffic-related pollution exposure at school and homes may both contribute to the development of asthma.

An analysis of asthma hospitalizations, air pollution, and weather conditions in Los Angeles County, California.

PubMed

Delamater, Paul L; Finley, Andrew O; Banerjee, Sudipto

2012-05-15

There is now a large body of literature supporting a linkage between exposure to air pollutants and asthma morbidity. However, the extent and significance of this relationship varies considerably between pollutants, location, scale of analysis, and analysis methods. Our primary goal is to evaluate the relationship between asthma hospitalizations, levels of ambient air pollution, and weather conditions in Los Angeles (LA) County, California, an area with a historical record of heavy air pollution. County-wide measures of carbon monoxide (CO), nitrogen dioxide (NO(2)), ozone (O(3)), particulate matter<10 μm (PM(10)), particulate matter<2.5 μm (PM(2.5)), maximum temperature, and relative humidity were collected for all months from 2001 to 2008. We then related these variables to monthly asthma hospitalization rates using Bayesian regression models with temporal random effects. We evaluated model performance using a goodness of fit criterion and predictive ability. Asthma hospitalization rates in LA County decreased between 2001 and 2008. Traffic-related pollutants, CO and NO(2), were significant and positively correlated with asthma hospitalizations. PM(2.5) also had a positive, significant association with asthma hospitalizations. PM(10), relative humidity, and maximum temperature produced mixed results, whereas O(3) was non-significant in all models. Inclusion of temporal random effects satisfies statistical model assumptions, improves model fit, and yields increased predictive accuracy and precision compared to their non-temporal counterparts. Generally, pollution levels and asthma hospitalizations decreased during the 9 year study period. Our findings also indicate that after accounting for seasonality in the data, asthma hospitalization rate has a significant positive relationship with ambient levels of CO, NO(2), and PM(2.5). Copyright © 2012 Elsevier B.V. All rights reserved.

ORMDL3 expression levels have no influence on the activity of serine palmitoyltransferase.

PubMed

Zhakupova, Assem; Debeuf, Nincy; Krols, Michiel; Toussaint, Wendy; Vanhoutte, Leen; Alecu, Irina; Kutalik, Zoltán; Vollenweider, Peter; Ernst, Daniela; von Eckardstein, Arnold; Lambrecht, Bart N; Janssens, Sophie; Hornemann, Thorsten

2016-12-01

ORMDL proteins are believed to be negative regulators of serine palmitoyltransferase (SPT), which catalyzes the first and rate limiting step in sphingolipid (SL) de novo synthesis. Several single-nucleotide polymorphisms (SNPs) that are close to the ORMDL3 locus have been reported to increase ORMDL3 expression and to be associated with an elevated risk for early childhood asthma; however, the direct effect of ORMDL3 expression on SPT activity and its link to asthma remains elusive. In this study, we investigated whether ORMDL3 expression is associated with changes in SPT activity and total SL levels. Ormdl3-knockout (Ormdl3 -/- ) and transgenic (Ormdl3 Tg/wt ) mice were generated to study the effect of ORMDL3 on total SL levels in plasma and tissues. Cellular SPT activity was measured in mouse embryonic fibroblasts from Ormdl3 -/- mice, as well as in HEK293 cells in which ORMDL3 was overexpressed and silenced. Furthermore, we analyzed the association of the reported ORMDL3 asthma SNPs with plasma sphingoid bases in a population-based cohort of 971 individuals. Total C 18 -long chain bases were not significantly altered in the plasma and tissues of Ormdl3 -/- mice, whereas C 18 -sphinganine showed a small and significant increase in plasma, lung, and liver tissues. Mouse embryonic fibroblast cells from Ormdl3 -/- mice did not show an altered SPT activity compared with Ormdl3 +/- and Ormdl3 +/+ mice. Overexpression or knockdown of ORMDL3 in HEK293 cells did not alter SPT activity; however, parallel knockdown of all 3 ORMDL isoforms increased enzyme activity significantly. A significant association of the annotated ORMDL3 asthma SNPs with plasma long-chain sphingoid base levels could not be confirmed. ORMDL3 expression levels seem not to be directly associated with changes in SPT activity. ORMDL3 might influence de novo sphingolipid metabolism downstream of SPT.-Zhakupova, A., Debeuf, N., Krols, M., Toussaint, W., Vanhoutte, L., Alecu, I., Kutalik, Z., Vollenweider, P., Ernst, D., von Eckardstein, A., Lambrecht, B. N., Janssens, S., Hornemann, T. ORMDL3 expression levels have no influence on the activity of serine palmitoyltransferase. © FASEB.

Pediatric asthma hospitalizations among urban minority children and the continuity of primary care.

PubMed

Utidjian, Levon H; Fiks, Alexander G; Localio, A Russell; Song, Lihai; Ramos, Mark J; Keren, Ron; Bell, Louis M; Grundmeier, Robert W

2017-12-01

To examine the effect of ambulatory health care processes on asthma hospitalizations. A retrospective cohort study using electronic health records was completed. Patients aged 2-18 years receiving health care from 1 of 5 urban practices between Jan 1, 2004 and Dec 31, 2008 with asthma documented on their problem list were included. Independent variables were modifiable health care processes in the primary care setting: (1) use of asthma controller medications; (2) regular assessment of asthma symptoms; (3) use of spirometry; (4) provision of individualized asthma care plans; (5) timely influenza vaccination; (6) access to primary healthcare; and (7) use of pay for performance physician incentives. Occurrence of one or more asthma hospitalizations was the primary outcome of interest. We used a log linear model (Poisson regression) to model the association between the factors of interest and number of asthma hospitalizations. 5,712 children with asthma were available for analysis. 96% of the children were African American. The overall hospitalization rate was 64 per 1,000 children per year. None of the commonly used asthma-specific indicators of high quality care were associated with fewer asthma hospitalizations. Children with documented asthma who experienced a lack of primary health care (no more than one outpatient visit at their primary care location in the 2 years preceding hospitalization) were at higher risk of hospitalization compared to those children with a greater number of visits (incidence rate ratio 1.39; 95% CI 1.09-1.78). In children with asthma, more frequent primary care visits are associated with reduced asthma hospitalizations.

Development, implementation, and evaluation of a community pharmacy-based asthma care model.

PubMed

Saini, Bandana; Krass, Ines; Armour, Carol

2004-11-01

Pharmacists are uniquely placed in the healthcare system to address critical issues in asthma management in the community. Various programs have shown the benefits of a pharmacist-led asthma care program; however, no such programs have previously been evaluated in Australia. To measure the impact of a specialized asthma service provided through community pharmacies in terms of objective patient clinical, humanistic, and economic outcomes. A parallel controlled design, where 52 intervention patients and 50 control patients with asthma were recruited in 2 distinct locations, was used. In the intervention area, pharmacists were trained and delivered an asthma care model, with 3 follow-up visits over 6 months. This model was evaluated based on clinical, humanistic, and economic outcomes compared between and within groups. There was a significant reduction in asthma severity in the intervention group, 2.6 +/- 0.5 to 1.6 +/- 0.7 (mean +/- SD; p < 0.001) versus the control group, 2.3 +/- 0.7 to 2.4 +/- 0.5. In the intervention group, peak flow indices improved from 82.7% +/- 8.2% at baseline to 87.4% +/- 8.9% (p < 0.001) at the final visit, and there was a significant reduction in the defined daily dose of albuterol used by patients, from 374.8 +/- 314.8 microg at baseline to 198.4 +/- 196.9 microg at the final visit (p < 0.015). There was also a statistically significant improvement in perceived control of asthma and asthma-related knowledge scores in the intervention group compared with the control group between baseline and the final visit. Annual savings of $132.84(AU) in medication costs per patient and $100,801.20 for the whole group, based on overall severity reduction, were demonstrated. Based on the results of this study, it appears that a specialized asthma care model offers community pharmacists an opportunity to contribute toward improving asthma management in the Australian community.

Body mass index trajectory classes and incident asthma in childhood: results from 8 European Birth Cohorts--a Global Allergy and Asthma European Network initiative.

PubMed

Rzehak, Peter; Wijga, Alet H; Keil, Thomas; Eller, Esben; Bindslev-Jensen, Carsten; Smit, Henriette A; Weyler, Joost; Dom, Sandra; Sunyer, Jordi; Mendez, Michelle; Torrent, Maties; Vall, Oriol; Bauer, Carl-Peter; Berdel, Dietrich; Schaaf, Beate; Chen, Chih-Mei; Bergström, Anna; Fantini, Maria P; Mommers, Monique; Wahn, Ulrich; Lau, Susanne; Heinrich, Joachim

2013-06-01

The causal link between body mass index (BMI) or obesity and asthma in children is still being debated. Analyses of large longitudinal studies with a sufficient number of incident cases and in which the time-dependent processes of both excess weight and asthma development can be validly analyzed are lacking. We sought to investigate whether the course of BMI predicts incident asthma in childhood. Data from 12,050 subjects of 8 European birth cohorts on asthma and allergies were combined. BMI and doctor-diagnosed asthma were modeled during the first 6 years of life with latent growth mixture modeling and discrete time hazard models. Subpopulations of children were identified with similar standardized BMI trajectories according to age- and sex-specific "World Health Organization (WHO) child growth standards" and "WHO growth standards for school aged children and adolescents" for children up to age 5 years and older than 5 years, respectively (BMI-SDS). These types of growth profiles were analyzed as predictors for incident asthma. Children with a rapid BMI-SDS gain in the first 2 years of life had a higher risk for incident asthma up to age 6 years than children with a less pronounced weight gain slope in early childhood. The hazard ratio was 1.3 (95% CI, 1.1-1.5) after adjustment for birth weight, weight-for-length at birth, gestational age, sex, maternal smoking in pregnancy, breast-feeding, and family history of asthma or allergies. A rapid BMI gain at 2 to 6 years of age in addition to rapid gain in the first 2 years of life did not significantly enhance the risk of asthma. Rapid growth in BMI during the first 2 years of life increases the risk of asthma up to age 6 years. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Adult-Onset Asthma Becomes the Dominant Phenotype among Women by Age 40 Years. The Longitudinal CARDIA Study

PubMed Central

Qualls, Clifford; Schuyler, Mark; Arynchyn, Alexander; Alvarado, Jesse H.; Smith, Lewis J.; Jacobs, David R.

2013-01-01

Rationale: Although asthma is usually considered to originate in childhood, adult-onset disease is being increasingly reported. Objectives: To contrast the proportion and natural history of adult-onset versus pediatric-onset asthma in a community-based cohort. We hypothesized that asthma in women is predominantly of adult onset rather than of pediatric onset. Methods: This study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort in the United States over a 25-year period. Adult- and pediatric-onset asthma phenotypes were studied, as defined by age at onset of 18 years or older. Subjects with asthma were categorized by sex, obesity, atopy, smoking, and race by mean age/examination year, using a three-way analysis of covariance model. Natural history of disease was examined using probabilities derived from a Markov chain model. Measurements and Main Results: Asthma of adult onset became the dominant (i.e., exceeded 50%) phenotype in women by age 40 years. The age by which adult-onset asthma became the dominant phenotype was further lowered for obese, nonatopic, ever-smoking, or white women. The prevalence trend with increasing time for adult-onset disease was greater among subjects with nonatopic than atopic asthma among both sexes. Furthermore, adult-onset asthma had remarkable sex-related differences in risk factors. In both sexes, the quiescent state for adult-onset asthma was less frequent and also “less stable” over time than for pediatric-onset asthma. Conclusions: Using a large national cohort, this study challenges the dictum that most asthma in adults originates in childhood. Studies of the differences between pediatric- and adult-onset asthma may provide greater insight into the phenotypic heterogeneity of asthma. PMID:23802814

Neighborhood poverty, urban residence, race/ethnicity, and asthma: Rethinking the inner-city asthma epidemic.

PubMed

Keet, Corinne A; McCormack, Meredith C; Pollack, Craig E; Peng, Roger D; McGowan, Emily; Matsui, Elizabeth C

2015-03-01

Although it is thought that inner-city areas have a high burden of asthma, the prevalence of asthma in inner cities across the United States is not known. We sought to estimate the prevalence of current asthma in US children living in inner-city and non-inner-city areas and to examine whether urban residence, poverty, or race/ethnicity are the main drivers of asthma disparities. The National Health Interview Survey 2009-2011 was linked by census tract to data from the US Census and the National Center for Health Statistics. Multivariate logistic regression models adjusted for sex; age; race/ethnicity; residence in an urban, suburban, medium metro, or small metro/rural area; poverty; and birth outside the United States, with current asthma and asthma morbidity as outcome variables. Inner-city areas were defined as urban areas with 20% or more of households at below the poverty line. We included 23,065 children living in 5,853 census tracts. The prevalence of current asthma was 12.9% in inner-city and 10.6% in non-inner-city areas, but this difference was not significant after adjusting for race/ethnicity, region, age, and sex. In fully adjusted models black race, Puerto Rican ethnicity, and lower household income but not residence in poor or urban areas were independent risk factors for current asthma. Household poverty increased the risk of asthma among non-Hispanics and Puerto Ricans but not among other Hispanics. Associations with asthma morbidity were very similar to those with prevalent asthma. Although the prevalence of asthma is high in some inner-city areas, this is largely explained by demographic factors and not by living in an urban neighborhood. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Predicting Children's Asthma Hospitalizations: Rural and Urban Differences in Texas

ERIC Educational Resources Information Center

Grineski, Sara E.

2009-01-01

Asthma is the number one chronic health condition facing children today; however, little is known about rural-urban inequalities in asthma. This "area effects on health" study examines rural-urban differences in childhood asthma hospitalizations within the state of Texas using negative binomial regression models. Effects associated with…

Are Neighborhood-Level Characteristics Associated with Indoor Allergens in the Household?

PubMed Central

Rosenfeld, Lindsay; Rudd, Rima; Chew, Ginger L.; Emmons, Karen; Acevedo-García, Dolores

2010-01-01

Background Individual home characteristics have been associated with indoor allergen exposure; however, the influence of neighborhood-level characteristics has not been well-studied. We defined neighborhoods as community districts determined by the New York Department of City Planning. Objective We examined the relationship between neighborhood-level characteristics and the presence of dust mite (Der f 1), cat (Fel d 1), cockroach (Bla g 2), and mouse (MUP) allergens in the household. Methods Using data from the Puerto Rican Asthma Project, a birth cohort of Puerto Rican children at risk of allergic sensitization (n=261) we examined associations between neighborhood characteristics (percent tree canopy, asthma hospitalizations per 1000 children, roadway length within 100 meters of buildings, serious housing code violations per 1000 rental units, poverty rates, and felony crime rates) and the presence of indoor allergens. Allergen cutpoints were used for categorical analyses and defined as follows: dust mite: >0.25 μg/g; cat: >1 μg/g; cockroach: >1 U/g; mouse: >1.6 μg/g. Results Serious housing code violations were statistically significantly positively associated with dust mite, cat and mouse allergens (continuous variables), adjusting for mother's income and education, and all neighborhood-level characteristics. In multivariable logistic regression analyses, medium levels of housing code violations were associated with higher dust mite and cat allergens (1.81, 95%CI: 1.08, 3.03 and 3.10, 95%CI: 1.22, 7.92, respectively). A high level of serious housing code violations was associated with higher mouse allergen (2.04, 95%CI: 1.15, 3.62). A medium level of housing code violations was associated with higher cockroach allergen (3.30, 95%CI: 1.11, 9.78). Conclusions Neighborhood-level characteristics, specifically housing code violations, appear to be related to indoor allergens, which may have implications for future research explorations and policy decisions. PMID:20100024

The use of remotely sensed environmental data in the study of asthma disease

NASA Astrophysics Data System (ADS)

Ayres-Sampaio, D.; Teodoro, A. C.; Freitas, A.; Sillero, N.

2012-09-01

Despite the growing use of Remote Sensing (RS) data in epidemiological studies, several diseases, including asthma, have not been studied yet using RS potentialities. Asthma is a chronic inflammatory disorder of the airway that affects people of all ages throughout the world. The expression of this disease can be influenced by some environmental factors such as allergens, air pollution or climate conditions. In this study, we modeled the distribution of asthma in each season, using Maximum entropy (Maxent) model and presence data obtained from a national database with asthma public hospitals admissions in Mainland Portugal, with discharges between years 2003 and 2008. We considered data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to retrieve estimates of near-surface air temperature and relative humidity. Land-use regression (LUR) models were developed to produce estimates of three pollutants: PM10, NO2, and CO. Moreover, MODIS Normalized Difference Vegetation Index (NDVI) was also used in the construction of Maxent models. All Maxent models predicted similar suitable areas and obtained acceptable area under the curve (AUC) values (~0.75) of the ROC plot. Our results show a strong relationship between asthma presence and NO2, suggesting that asthmatic people living in urban areas with high traffic volume have an increased risk of suffering asthma attacks. Furthermore, there is evidence of the effect of PM10, CO, and RH (during the Summer) in asthma expression. RS data have a great potential but also presents limitations that should be addressed to allow studying more complex diseases.

Exercise Training, Lymphocyte Subsets and Their Cytokines Production: Experience of an Italian Professional Football Team and Their Impact on Allergy

PubMed Central

2014-01-01

Background. In recent years, numerous articles have attempted to shed light on our understanding of the pathophysiological mechanisms of exercise-induced immunologic changes and their impact on allergy and asthma. It is known that lymphocyte subclasses, cytokines, and chemokines show modifications after exercise, but outcomes can be affected by the type of exercise as well as by its intensity and duration. Interesting data have been presented in many recent studies on mouse models, but few studies on humans have been performed to check the long-term effects of exercise over a whole championship season. Methods. This study evaluated lymphocyte subsets and their intracellular IL-2, IL-4, TNF-α, and IFN-γ production in professional football (soccer) players, at three stages of the season, to evaluate if alterations occur, particularly in relation to their allergic status. Results and Conclusion. Despite significant mid-season alterations, no significant lymphocyte subclasses count modifications, except for NKs that were significantly higher, were observed at the end. IL-2 and IL-4 producing cells showed a significant decrease (P = 0.018 and P = 0.001, but in a steady fashion for IL-4), confirming the murine data about the potential beneficial effects of aerobic exercise for allergic asthma. PMID:25050349

Exercise training, lymphocyte subsets and their cytokines production: experience of an Italian professional football team and their impact on allergy.

PubMed

Del Giacco, Stefano R; Scorcu, Marco; Argiolas, Federico; Firinu, Davide; Del Giacco, G Sergio

2014-01-01

In recent years, numerous articles have attempted to shed light on our understanding of the pathophysiological mechanisms of exercise-induced immunologic changes and their impact on allergy and asthma. It is known that lymphocyte subclasses, cytokines, and chemokines show modifications after exercise, but outcomes can be affected by the type of exercise as well as by its intensity and duration. Interesting data have been presented in many recent studies on mouse models, but few studies on humans have been performed to check the long-term effects of exercise over a whole championship season. This study evaluated lymphocyte subsets and their intracellular IL-2, IL-4, TNF-α, and IFN-γ production in professional football (soccer) players, at three stages of the season, to evaluate if alterations occur, particularly in relation to their allergic status. Despite significant mid-season alterations, no significant lymphocyte subclasses count modifications, except for NKs that were significantly higher, were observed at the end. IL-2 and IL-4 producing cells showed a significant decrease (P = 0.018 and P = 0.001, but in a steady fashion for IL-4), confirming the murine data about the potential beneficial effects of aerobic exercise for allergic asthma.

Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

PubMed Central

Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

2015-01-01

Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

Associations between Neighborhood Walkability and Incident and Ongoing Asthma in Children.

PubMed

Simons, Elinor; Dell, Sharon D; Moineddin, Rahim; To, Teresa

2018-06-01

Childhood asthma has shown variable associations with children's physical activity. Neighborhood walkability captures community features that promote walking and is protective against some chronic conditions, such as obesity and diabetes. We evaluated associations between home neighborhood walkability and incident and ongoing childhood asthma. In this population-based cohort study, we used prospectively collected administrative healthcare data for the Province of Ontario housed at the Institute for Clinical Evaluative Sciences. We followed an administrative data cohort of 326,383 Toronto children born between 1997 and 2003, inclusive, until ages 8-15 years. Home neighborhood walkability quintile was measured using a validated walkability index with four dimensions: population density, dwelling density, access to retail and services, and street connectivity. Incident asthma was defined by time of entry into the validated Ontario Asthma Surveillance Information System database, which requires two outpatient visits for asthma within two consecutive years or any hospitalization for asthma and follows children with asthma longitudinally starting at any age. Associations between walkability and incident asthma were examined using Cox proportional hazards models. Associations between ongoing asthma and walkability in each year of life were examined using generalized linear mixed models. Twenty-one percent of children (n = 69,628) developed incident asthma and were followed longitudinally in the Ontario Asthma Surveillance Information System database. Low birth home neighborhood walkability was associated with an increased incidence of asthma (hazard ratio, 1.11; 95% confidence interval, 1.08-1.14). Among children with asthma, low walkability in a given year of a child`s life was associated with greater odds of ongoing asthma in the same year (odds ratio, 1.12; 95% confidence interval, 1.09-1.14). Children living in neighborhoods with low walkability were at increased risk of incident and ongoing asthma. Neighborhood walkability improvement, such as by adding pedestrian paths to improve street connectivity, offers potential strategies to contribute to primary asthma prevention.

The association between asthma and absenteeism among working adults in the United States: results from the 2008 medical expenditure panel survey.

PubMed

Wu, Chung-Hsuen; Erickson, Steven R

2012-09-01

The purpose of this study was to evaluate the association between asthma status and the occurrence and length of work absences among the US working adults. A cross-sectional study was conducted using the 2008 Medical Expenditure Panel Survey (MEPS). Employed respondents between ages 18 and 55 years were included. The association between asthma status (whether respondents have asthma or not) and occurrence of absences and the length of time per absence was evaluated using a two-part model. A multivariate logistic regression as the first part of the model was to estimate the probability of being absent from work at least once during the observation period as a function of asthma status. A multivariate negative binomial regression as the second part of the model was used to assess whether the length of each absence from work was associated with asthma status among respondents who reported at least one absence from work. Sociodemographic, socioeconomic, employment-related, health status, and comorbidity variables were included in each model as covariates. Of 12,161 respondents, 8.2% reported having asthma, which accounted for 10.4 million working adults in the United States in 2008. Employed adults with asthma were more likely to report having at least one absence from work compared to those without asthma in bivariate analyses (26.2% vs. 16.2%, p < .01). After adjusting for the number of comorbid chronic conditions and other covariates, there was no significant difference between having asthma and absenteeism among respondents (odds ratio (OR) = 1.31, 95% confidence interval (CI) = 0.99-1.72, rate ratio (RR) = 1.25, 95% CI = 0.91-1.72). Overall burden of illness as measured by comorbidity indices and perceived health status, but not asthma alone, contributes to absenteeism as well as the number of days off during each occurrence among employed people. It is important for health services researchers to consider overall burden of illness when examining the association between a general outcome such as absence from work and specific conditions such as asthma.

Downregulation of glutathione S-transferase pi in asthma contributes to enhanced oxidative stress.

PubMed

Schroer, Kathy T; Gibson, Aaron M; Sivaprasad, Umasundari; Bass, Stacey A; Ericksen, Mark B; Wills-Karp, Marsha; Lecras, Tim; Fitzpatrick, Anne M; Brown, Lou Ann S; Stringer, Keith F; Hershey, Gurjit K Khurana

2011-09-01

Glutathione S-transferase pi (GSTPi) is the predominant redox regulator in the lung. Although evidence implicates an important role for GSTPi in asthma, the mechanism for this has remained elusive. We sought to determine how GSTPi is regulated in asthma and to elucidate its role in maintaining redox homeostasis. We elucidated the regulation of GSTPi in children with asthma and used murine models of asthma to determine the role of GSTPi in redox homeostasis. Our findings demonstrate that GSTPi transcript levels are markedly downregulated in allergen- and IL-13-treated murine models of asthma through signal transducer and activator of transcription 6-dependent and independent pathways. Nuclear factor erythroid 2-related factor 2 was also downregulated in these models. The decrease in GSTPi expression was associated with decreased total glutathione S-transferase activity in the lungs of mice. Examination of cystine intermediates uncovered a functional role for GSTPi in regulating cysteine oxidation, whereby GSTPi-deficient mice exhibited increased oxidative stress (increase in percentage cystine) compared with wild-type mice after allergen challenge. GSTPi expression was similarly downregulated in children with asthma. These data collectively suggest that downregulation of GSTPi after allergen challenge might contribute to the asthma phenotype because of disruption of redox homeostasis and increased oxidative stress. Furthermore, GSTPi might be an important therapeutic target for asthma, and evaluation of GSTPi expression might prove beneficial in identifying patients who would benefit from therapy targeting this pathway. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal factors.

PubMed

Wen, Hui-Ju; Chiang, Tung-Liang; Lin, Shio-Jean; Guo, Yue Leon

2015-05-01

Symptoms of atopic disease start early in human life. Predicting risk for childhood asthma by early-life exposure would contribute to disease prevention. A birth cohort study was conducted to investigate early-life risk factors for childhood asthma and to develop a predictive model for the development of asthma. National representative samples of newborn babies were obtained by multistage stratified systematic sampling from the 2005 Taiwan Birth Registry. Information on potential risk factors and children's health was collected by home interview when babies were 6 months old and 5 yr old, respectively. Backward stepwise regression analysis was used to identify the risk factors of childhood asthma for predictive models that were used to calculate the probability of childhood asthma. A total of 19,192 children completed the study satisfactorily. Physician-diagnosed asthma was reported in 6.6% of 5-yr-old children. Pre-pregnancy factors (parental atopy and socioeconomic status), perinatal factors (place of residence, exposure to indoor mold and painting/renovations during pregnancy), and postnatal factors (maternal postpartum depression and the presence of atopic dermatitis before 6 months of age) were chosen for the predictive models, and the highest predicted probability of asthma in 5-yr-old children was 68.1% in boys and 78.1% in girls; the lowest probability in boys and girls was 4.1% and 3.2%, respectively. This investigation provides a technique for predicting risk of childhood asthma that can be used to developing a preventive strategy against asthma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Role of COX-2 in the Inflammatory and Fibrotic Response in the Lung Following Exposure to Multi-Walled Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Sayers, Brian C.

Exposure to multiwalled carbon nanotubes (MWCNT) has been demonstrated to exacerbate airway inflammation and fibrosis in allergen-challenged mouse model. These data have led to concern that individuals with asthma could represent a susceptible population to adverse health effects following exposure to MWCNT, and possibly other engineered nanoparticles. Asthma pathogenesis is caused by the interaction of a complex genetic predisposition and environmental exposures. Because chronic airway inflammation is common to all asthma phenotypes, it is logical to investigate genes that are involved in inflammatory pathways in order to understand the genetic basis of asthma. The metabolism of arachidonic acid by cyclooxygenase (COX) enzymes is the rate-determining step in the synthesis of prostanoids, which are biologically active lipids that are important modulators of inflammation. Based on the role of COX enzymes in inflammatory pathways, we sought to investigate how COX enzymes are involved in the inflammatory response following MWCNT exposure in asthmatic airways. We report that MWCNT significantly exacerbated allergen-induced airway inflammation and mucus cell metaplasia in COX-2 deficient mice compared to wild type mice. In addition, MWCNTs significantly enhanced allergen-induced cytokines involved in Th2 (IL-13, IL-5), Th1 (CXCL10), and Th17 (IL-17A) inflammatory responses in COX-2 deficient mice but not in WT mice. We conclude that exacerbation of allergen-induced airway inflammation and mucus cell metaplasia by MWCNTs is enhanced by deficiency in COX-2 and associated with activation of a mixed Th1/Th2/Th17 immune response. Based on our observation that COX-2 deficient mice developed a mixed Th immune response following MWCNT exposure, we sought to evaluate how cytokines associated with different Th immune responses alter COX expression following MWCNT exposure. For this study, a mouse macrophage cell line (RAW264.7) was used because MWCNT were largely sequestered within alveolar macrophages with 24 hours after aspiration in mice. We report that the Th1 cytokine interferon gamma (IFNgamma) causes decreased COX-1 expression but increased prostaglandin E2 (PGE 2) production in mouse macrophages exposed to nickel nanoparticles (NiNP), a residual impurity found in MWCNT from the catalytic synthesis process. NiNP exposure alone increased COX-2 and decreased COX-1 in the absence of exogenous cytokines. IFNgamma further reduced COX-1 levels suppressed by NiNP. IL-4, IL-13, or IL-17 did not reduce COX-1 expression alone or in combination with NiNP. Exogenous PGE2 enhanced NiNP- or IFN-gamma-mediated COX-1 suppression. Pharmacologic inhibition of ERK1,2 or JAK/STAT-1 cell signaling pathways inhibited PGE2 production in all dose groups and restored COX-1 expression in cells treated with IFNgamma and NiNP. These data show that PGE2 production is induced in macrophages exposed to IFNgamma and NiNP and suggest that macrophages could be an important source of the anti-inflammatory mediator PGE2 following nanoparticle exposure in a Th1 immune microenvironment. In summary, these studies highlight an important role for COX enzymes in regulating inflammation in response to engineered nanoparticles and show that prostanoid production in response to nanoparticle exposure could be determined in part by the Th immune microenvironment.

Beyond Reading Alone: The Relationship Between Aural Literacy And Asthma Management

PubMed Central

Rosenfeld, Lindsay; Rudd, Rima; Emmons, Karen M.; Acevedo-García, Dolores; Martin, Laurie; Buka, Stephen

2010-01-01

Objectives To examine the relationship between literacy and asthma management with a focus on the oral exchange. Methods Study participants, all of whom reported asthma, were drawn from the New England Family Study (NEFS), an examination of links between education and health. NEFS data included reading, oral (speaking), and aural (listening) literacy measures. An additional survey was conducted with this group of study participants related to asthma issues, particularly asthma management. Data analysis focused on bivariate and multivariable logistic regression. Results In bivariate logistic regression models exploring aural literacy, there was a statistically significant association between those participants with lower aural literacy skills and less successful asthma management (OR:4.37, 95%CI:1.11, 17.32). In multivariable logistic regression analyses, controlling for gender, income, and race in separate models (one-at-a-time), there remained a statistically significant association between those participants with lower aural literacy skills and less successful asthma management. Conclusion Lower aural literacy skills seem to complicate asthma management capabilities. Practice Implications Greater attention to the oral exchange, in particular the listening skills highlighted by aural literacy, as well as other related literacy skills may help us develop strategies for clear communication related to asthma management. PMID:20399060

Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model.

PubMed

Taher, Yousef A; Piavaux, Benoit J A; Gras, Reneé; van Esch, Betty C A M; Hofman, Gerard A; Bloksma, Nanne; Henricks, Paul A J; van Oosterhout, Antoon J M

2008-04-01

The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive effects on asthma manifestations and (2) whether tryptophan depletion or generation of its downstream metabolites is involved. Ovalbumin (OVA)-sensitized and OVA-challenged BALB/c mice that display increased airway responsiveness to methacholine, serum OVA-specific IgE levels, bronchoalveolar eosinophilia, and TH2 cytokine levels were used as a model of allergic asthma. Sensitized mice received subcutaneous optimal (1 mg) or suboptimal (100 microg) OVA immunotherapy. Inhibition of IDO by 1-methyl-DL-tryptophan during immunotherapy, but not during inhalation challenge, partially reversed the suppressive effects of immunotherapy on airway eosinophilia and TH2 cytokine levels, whereas airway hyperresponsiveness and serum OVA-specific IgE levels remained suppressed. Administration of tryptophan during immunotherapy failed to abrogate its beneficial effects toward allergic airway inflammation. Interestingly, administration of tryptophan or its metabolites, kynurenine, 3-hydroxykynurenine, and xanthurenic acid, but not 3-hydroxyanthranilinic acid, quinolinic acid, and kynurenic acid, during suboptimal immunotherapy potentiated the reduction of eosinophilia. These effects coincided with reduced TH2 cytokine levels in bronchoalveolar lavage fluid, but no effects on IgE levels were detected. During immunotherapy, the tryptophan metabolites kynurenine, 3-hydroxykynurenine, and xanthurenic acid generated through IDO contribute to tolerance induction regarding TH2-dependent allergic airway inflammation.

Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease.

PubMed

Royce, Simon G; Dang, William; Ververis, Katherine; De Sampayo, Nishika; El-Osta, Assam; Tang, Mimi L K; Karagiannis, Tom C

2011-12-01

Airway remodeling and airway hyperresponsiveness are major aspects of asthma pathology that are not targeted optimally by existing anti-inflammatory drugs. Histone deacetylase inhibitors have a wide range of effects that may potentially abrogate aspects of remodeling. One such histone deacetylase inhibitor is valproic acid (2-propylvaleric acid). Valproic acid is used clinically as an anti-epileptic drug and is a potent inhibitor of class I histone deacetylases but also inhibits class II histone deacetylases. We used valproic acid as a molecular model of histone deacetylase inhibition in vivo in chronic allergic airways disease mice with airway remodeling and airway hyperresponsiveness. Wild-type Balb/c mice with allergic airways disease were treated with valproic acid or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and examination of lung tissue sections. Remodeling was assessed by morphometric analysis of histochemically stained slides and lung function was assessed by invasive plethysmography measurement of airway resistance. Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest doses of methacholine, respectively). These findings show that treatment with valproic acid can reduce structural airway remodeling changes and hyperresponsiveness, providing further evidence for the potential use of histone deacetylase inhibitors for the treatment of asthma.

The public health implications of asthma.

PubMed Central

Bousquet, Jean; Bousquet, Philippe J.; Godard, Philippe; Daures, Jean-Pierre

2005-01-01

Asthma is a very common chronic disease that occurs in all age groups and is the focus of various clinical and public health interventions. Both morbidity and mortality from asthma are significant. The number of disability-adjusted life years (DALYs) lost due to asthma worldwide is similar to that for diabetes, liver cirrhosis and schizophrenia. Asthma management plans have, however, reduced mortality and severity in countries where they have been applied. Several barriers reduce the availability, affordability, dissemination and efficacy of optimal asthma management plans in both developed and developing countries. The workplace environment contributes significantly to the general burden of asthma. Patients with occupational asthma have higher rates of hospitalization and mortality than healthy workers. The surveillance of asthma as part of a global WHO programme is essential. The economic cost of asthma is considerable both in terms of direct medical costs (such as hospital admissions and the cost of pharmaceuticals) and indirect medical costs (such as time lost from work and premature death). Direct costs are significant in most countries. In order to reduce costs and improve quality of care, employers and health plans are exploring more precisely targeted ways of controlling rapidly rising health costs. Poor control of asthma symptoms is a major issue that can result in adverse clinical and economic outcomes. A model of asthma costs is needed to aid attempts to reduce them while permitting optimal management of the disease. This paper presents a discussion of the burden of asthma and its socioeconomic implications and proposes a model to predict the costs incurred by the disease. PMID:16175830

Asthma Management in Minority Children: Practical Insights for Clinicians, Researchers, and Public Health Planners.

ERIC Educational Resources Information Center

National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

This monograph summarizes asthma management conclusions developed by five studies funded under a 5-year federal program titled "Interventions for the Control of Asthma among Black and Hispanic Children." The research goals were to develop model, replicable programs to reduce asthma morbidity; decrease inappropriate use of health care…

Neighborhood Poverty, Urban Residence, Race/ethnicity and Asthma: Rethinking the Inner-city Asthma Epidemic

PubMed Central

Keet, Corinne A.; McCormack, Meredith C.; Pollack, Craig E.; Peng, Roger D.; McGowan, Emily; Matsui, Elizabeth C.

2015-01-01

Background Although it is thought that inner-city areas have a high burden of asthma, the prevalence of asthma in inner-cities across the U.S. is not known. Objective To estimate the prevalence of current asthma in U.S. children living in inner-city and non-inner city areas, and to examine whether urban residence, poverty or race/ethnicity are the main drivers of asthma disparities. Methods The National Health Interview Survey 2009–2011 was linked by census tract to data from the U.S. Census and the National Center for Health Statistics. Multivariate logistic regression models adjusted for sex, age, race/ethnicity, residence in an urban, suburban, medium metro or small metro/rural area, poverty, and birth outside the U.S. with current asthma and asthma morbidity as outcome variables. Inner-city areas were defined as urban areas with ≥20% of households below the poverty line. Results 23,065 children living in 5,853 census tracts were included. The prevalence of current asthma was 12.9% in inner-city and 10.6% in non-inner-city areas, but this difference was not significant after adjusting for race/ethnicity, region, age and sex. In fully adjusted models, Black race, Puerto Rican ethnicity and lower household income, but not residence in poor or urban areas, were independent risk factors for current asthma. Household poverty increased the risk of asthma among non-Hispanics and Puerto Ricans but not among other Hispanics. Associations with asthma morbidity were very similar to prevalent asthma. Conclusions Although the prevalence of asthma is high in some inner-city areas, this is largely explained by demographic factors and not by living in an urban neighborhood. PMID:25617226

TRPV1 Blocking Alleviates Airway Inflammation and Remodeling in a Chronic Asthma Murine Model.

PubMed

Choi, Joon Young; Lee, Hwa Young; Hur, Jung; Kim, Kyung Hoon; Kang, Ji Young; Rhee, Chin Kook; Lee, Sook Young

2018-05-01

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. There is emerging interest in the involvement of the transient receptor potential vanilloid 1 (TRPV1) channel in the pathophysiology of asthma. This study examined whether TRPV1 antagonism alleviates asthma features in a murine model of chronic asthma. BALB/c mice were sensitized to and challenged by ovalbumin to develop chronic asthma. Capsazepine (TRPV1 antagonist) or TRPV1 small interfering RNA (siRNA) was administered in the treatment group to evaluate the effect of TPV1 antagonism on AHR, airway inflammation, and remodeling. The mice displayed increased AHR, airway inflammation, and remodeling. Treatment with capsazepine or TRPV1 siRNA reduced AHR to methacholine and airway inflammation. Type 2 T helper (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13) were reduced and epithelial cell-derived cytokines (thymic stromal lymphopoietin [TSLP], IL-33, and IL-25), which regulate Th2 cytokine-associated inflammation, were also reduced. Airway remodeling characterized by goblet cell hyperplasia, increased α-smooth muscle action, and collagen deposition was also alleviated by both treatments. Treatment directed at TRPV1 significantly alleviated AHR, airway inflammation, and remodeling in a chronic asthma murine model. The TRPV1 receptor can be a potential drug target for chronic bronchial asthma. Copyright © 2018 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.

A simulation model of building intervention impacts on indoor environmental quality, pediatric asthma, and costs.

PubMed

Fabian, Maria Patricia; Adamkiewicz, Gary; Stout, Natasha Kay; Sandel, Megan; Levy, Jonathan Ian

2014-01-01

Although indoor environmental conditions can affect pediatric asthmatic patients, few studies have characterized the effect of building interventions on asthma-related outcomes. Simulation models can evaluate such complex systems but have not been applied in this context. We sought to evaluate the impact of building interventions on indoor environmental quality and pediatric asthma health care use, and to conduct cost comparisons between intervention and health care costs and energy savings. We applied our previously developed discrete event simulation model (DEM) to simulate the effect of environmental factors, medication compliance, seasonality, and medical history on (1) pollutant concentrations indoors and (2) asthma outcomes in low-income multifamily housing. We estimated health care use and costs at baseline and subsequent to interventions, and then compared health care costs with energy savings and intervention costs. Interventions, such as integrated pest management and repairing kitchen exhaust fans, led to 7% to 12% reductions in serious asthma events with 1- to 3-year payback periods. Weatherization efforts targeted solely toward tightening a building envelope led to 20% more serious asthma events, but bundling with repairing kitchen exhaust fans and eliminating indoor sources (eg, gas stoves or smokers) mitigated this effect. Our pediatric asthma model provides a tool to prioritize individual and bundled building interventions based on their effects on health and costs, highlighting the tradeoffs between weatherization, indoor air quality, and health. Our work bridges the gap between clinical and environmental health sciences by increasing physicians' understanding of the effect that home environmental changes can have on their patients' asthma. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.

PubMed

Rigas, Diamanda; Lewis, Gavin; Aron, Jennifer L; Wang, Bowen; Banie, Homayon; Sankaranarayanan, Ishwarya; Galle-Treger, Lauriane; Maazi, Hadi; Lo, Richard; Freeman, Gordon J; Sharpe, Arlene H; Soroosh, Pejman; Akbari, Omid

2017-05-01

Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function. ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity. We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model. These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Pseudotyped adeno-associated virus 2/9-delivered CCL11 shRNA alleviates lung inflammation in an allergen-sensitized mouse model.

PubMed

Wu, Chia-Jen; Huang, Wen-Chung; Chen, Li-Chen; Shen, Chia-Rui; Kuo, Ming-Ling

2012-11-01

Airway infiltration by eosinophils is a major characteristic of chronic asthma. CCL11 (eotaxin-1) is secreted by lung epithelial cells and functions as the major chemokine for eosinophil recruitment. Pseudotyped adeno-associated virus (AAV) 2/9, composed by the AAV2 rep and AAV9 cap genes, can efficiently target lung epithelial cells and might carry gene sequences with therapeutic potential for asthma. This study aimed to determine whether pseudotyped AAV2/9 virus carrying the small hairpin RNA targeting CCL11 and expressed by CMV/U6 promoter could reduce eosinophilia and asthmatic responses in mite allergen-sensitized mice. Mice were sensitized by intraperitoneal and challenged by intratracheal injection with recombinant Dermatophagoides pteronyssinus group 2 allergen (rDp2). AAV2/9 viral vectors were intratracheally injected three days before the first challenge. AAV2/9 sh47 virus significantly reduced airway hyperresponsiveness, airway resistance, CCL11 levels, and eosinophilia in the lungs of sensitized mice. Th2 cytokines, including interleukins (IL)-4, IL-5, and IL-10, were also significantly reduced in the bronchoalveolar lavage fluid of AAV2/9 sh47 virus-treated mice. Th2 cytokine levels were also reduced in rDp2-stimulated mediastinal lymphocytes in treated mice. However, serum levels of rDp2-specific IgG1 and IgE, as well as Th2 cytokine levels in rDp2-stimulated splenocyte culture supernatants, were comparable to the sensitized control group. The results suggest that AAV2/9 sh47 virus relieved local instead of systemic inflammatory responses. Therefore, the CMV/U6 promoter with AAV2/9 viral vector, which is preferable to target lung epithelia cells, might be applied as a novel therapeutic approach for asthma.

Pseudotyped Adeno-Associated Virus 2/9-Delivered CCL11 shRNA Alleviates Lung Inflammation in an Allergen-Sensitized Mouse Model

PubMed Central

Wu, Chia-Jen; Huang, Wen-Chung; Chen, Li-Chen; Shen, Chia-Rui

2012-01-01

Abstract Airway infiltration by eosinophils is a major characteristic of chronic asthma. CCL11 (eotaxin-1) is secreted by lung epithelial cells and functions as the major chemokine for eosinophil recruitment. Pseudotyped adeno-associated virus (AAV) 2/9, composed by the AAV2 rep and AAV9 cap genes, can efficiently target lung epithelial cells and might carry gene sequences with therapeutic potential for asthma. This study aimed to determine whether pseudotyped AAV2/9 virus carrying the small hairpin RNA targeting CCL11 and expressed by CMV/U6 promoter could reduce eosinophilia and asthmatic responses in mite allergen-sensitized mice. Mice were sensitized by intraperitoneal and challenged by intratracheal injection with recombinant Dermatophagoides pteronyssinus group 2 allergen (rDp2). AAV2/9 viral vectors were intratracheally injected three days before the first challenge. AAV2/9 sh47 virus significantly reduced airway hyperresponsiveness, airway resistance, CCL11 levels, and eosinophilia in the lungs of sensitized mice. Th2 cytokines, including interleukins (IL)-4, IL-5, and IL-10, were also significantly reduced in the bronchoalveolar lavage fluid of AAV2/9 sh47 virus-treated mice. Th2 cytokine levels were also reduced in rDp2-stimulated mediastinal lymphocytes in treated mice. However, serum levels of rDp2-specific IgG1 and IgE, as well as Th2 cytokine levels in rDp2-stimulated splenocyte culture supernatants, were comparable to the sensitized control group. The results suggest that AAV2/9 sh47 virus relieved local instead of systemic inflammatory responses. Therefore, the CMV/U6 promoter with AAV2/9 viral vector, which is preferable to target lung epithelia cells, might be applied as a novel therapeutic approach for asthma. PMID:22913580

IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

PubMed Central

Devos, Fien C.; Pollaris, Lore; Cremer, Jonathan; Seys, Sven; Hoshino, Tomoaki; Ceuppens, Jan; Talavera, Karel; Nemery, Benoit; Hoet, Peter H. M.

2017-01-01

Background While the importance of the Th2 cytokine IL-13 as a central mediator of airway hyperreactivity (AHR) has been described in allergic protein-induced asthma, this has never been investigated in chemical-induced asthma. Objective We examined the importance of IL-13 in a mouse model of chemical-induced AHR, using toluene-2,4-diisocyanate (TDI). Methods In a first set-up, wild type (WT) and IL-13 knockout (KO) C57Bl/6 mice were dermally treated on days 1 and 8 with 1% TDI or vehicle (acetone/olive oil) on both ears. On day 15, mice received an intranasal instillation with 0.1% TDI or vehicle. In a second set-up, WT mice sensitized with 1% TDI or vehicle, received i.v. either anti-IL-13 or control antibody prior to the intranasal challenge. Results TDI-sensitized and TDI-challenged WT mice showed AHR to methacholine, in contrast to TDI-sensitized and TDI-challenged IL-13 KO mice, which also showed lower levels of total serum IgE. TDI-sensitized and TDI-challenged IL-13 KO mice had lower numbers of T-cells in the auricular lymph nodes. TDI-treated WT mice, receiving anti-IL-13, showed no AHR, in contrast to those receiving control antibody, despite increased levels of IgE. Anti-IL-13 treatment in TDI-treated WT mice resulted in lower levels of serum IL-13, but did not induce changes in T- and B-cell numbers, and in the cytokine production profile. Conclusion and clinical relevance We conclude that IL-13 plays a critical role in the effector phase of chemical-induced, immune-mediated AHR. This implicates that anti-IL-13 treatment could have a beneficial effect in patients with this asthma phenotype. PMID:28704401

Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells

PubMed Central

Huff, Ryan D.; Hsu, Alan C-Y.; Nichol, Kristy S.; Jones, Bernadette; Knight, Darryl A.; Wark, Peter A. B.; Hansbro, Philip M.

2017-01-01

Introduction The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Materials and methods Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. Results HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Conclusions Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines. PMID:28863172

Polo-like Kinase 1 Regulates Vimentin Phosphorylation at Ser-56 and Contraction in Smooth Muscle*

PubMed Central

Li, Jia; Wang, Ruping; Gannon, Olivia J.; Rezey, Alyssa C.; Jiang, Sixin; Gerlach, Brennan D.; Liao, Guoning

2016-01-01

Polo-like kinase 1 (Plk1) is a serine/threonine-protein kinase that has been implicated in mitosis, cytokinesis, and smooth muscle cell proliferation. The role of Plk1 in smooth muscle contraction has not been investigated. Here, stimulation with acetylcholine induced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activated Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor. Moreover, knockdown of Plk1 in smooth muscle attenuated force development. Smooth muscle conditional knock-out of Plk1 also diminished contraction of mouse tracheal rings. Plk1 knockdown inhibited acetylcholine-induced vimentin phosphorylation at Ser-56 without affecting myosin light chain phosphorylation. Expression of T210A Plk1 inhibited the agonist-induced vimentin phosphorylation at Ser-56 and contraction in smooth muscle. However, myosin light chain phosphorylation was not affected by T210A Plk1. Ste20-like kinase (SLK) is a serine/threonine-protein kinase that has been implicated in spindle orientation and microtubule organization during mitosis. In this study knockdown of SLK inhibited Plk1 phosphorylation at Thr-210 and activation. Finally, asthma is characterized by airway hyperresponsiveness, which largely stems from airway smooth muscle hyperreactivity. Here, smooth muscle conditional knock-out of Plk1 attenuated airway resistance and airway smooth muscle hyperreactivity in a murine model of asthma. Taken together, these findings suggest that Plk1 regulates smooth muscle contraction by modulating vimentin phosphorylation at Ser-56. Plk1 activation is regulated by SLK during contractile activation. Plk1 contributes to the pathogenesis of asthma. PMID:27662907

Sea Cucumber Lipid-Soluble Extra Fraction Prevents Ovalbumin-Induced Allergic Airway Inflammation.

PubMed

Lee, Da-In; Kang, Shin Ae; Md, Anisuzzaman; Jeong, U-Cheol; Jin, Feng; Kang, Seok-Joong; Lee, Jeong-Yeol; Yu, Hak Sun

2018-01-01

In a previous study, our research group demonstrated that sea cucumber (Apostichopus japonicus) extracts ameliorated allergic airway inflammation through CD4 + CD25 + Foxp3 + T (regulatory T; Treg) cell activation and recruitment to the lung. In this study, we aimed to determine which components of sea cucumber contribute to the amelioration of airway inflammation. We used n-hexane fractionation to separate sea cucumber into three phases (n-hexane, alcohol, and solid) and evaluated the ability of each phase to elevate Il10 expression in splenocytes and ameliorate symptoms in mice with ovalbumin (OVA)/alum-induced asthma. Splenocytes treated with the n-hexane phase showed a significant increase in Il10 expression. In the n-hexane phase, 47 fatty acids were identified. Individual fatty acids that comprised at least 5% of the total fatty acids were 16:0, 16:1n-7, 18:0, 18:1n-7, 20:4n-6, and 20:5n-3 (eicosapentaenoic acid). After administering the n-hexane phase to mice with OVA/alum-induced asthma, their asthma symptoms were ameliorated. Several immunomodulatory effects were observed in the n-hexane phase-pretreated group, compared with a vehicle control group. First, eosinophil infiltration and goblet cell hyperplasia were significantly reduced around the airways. Second, the concentrations of Th2-related cytokines (IL-4, IL-5, and IL-13) and Th17-related cytokines (IL-17) were significantly decreased in the spleen and bronchoalveolar lavage fluid (BALF). Finally, the concentrations of TGF-β and IL-10, which are associated with Treg cells, were significantly increased in the BALF and splenocyte culture medium. In conclusion, a fatty acid-rich fraction (n-hexane phase) of sea cucumber extract ameliorated allergic airway inflammation in a mouse model.

Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice.

PubMed

Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Fernandes, Lynette B; Zosky, Graeme R; Sly, Peter D; Larcombe, Alexander N

2014-01-01

Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle) daily for 10 days. On day 9, mice were inoculated with human-rhinovirus-1B (or UV-inactivated human-rhinovirus-1B). Forty-eight hours after inoculation, we assessed bronchoalveolar cellular inflammation, levels of relevant cytokines/serum antibodies, lung function and responsiveness/sensitivity to methacholine. House-dust-mite exposure did not result in a classical TH2-driven response, but was more representative of noneosinophilic asthma. However, there were significant effects of house-dust-mite exposure on most of the parameters measured including increased cellular inflammation (primarily macrophages and neutrophils), increased total IgE and house-dust-mite-specific IgG1 and increased responsiveness/sensitivity to methacholine. There were limited effects of human-rhinovirus-1B infection alone, and the combination of the two insults resulted in additive increases in neutrophil levels and lung parenchymal responses to methacholine (tissue elastance). We conclude that acute rhinovirus infection exacerbates house-dust-mite-induced lung disease in adult mice. The similarity of our results using the naturally occurring allergen house-dust-mite, to previous studies using ovalbumin, suggests that the exacerbation of allergic airways disease by rhinovirus infection could act via multiple or conserved mechanisms.

Revisiting the Hispanic health paradox: the relative contributions of nativity, country of origin, and race/ethnicity to childhood asthma.

PubMed

Camacho-Rivera, Marlene; Kawachi, Ichiro; Bennett, Gary G; Subramanian, S V

2015-06-01

This study examined the relationship between race and Hispanic ethnicity, maternal and child nativity, country of origin and asthma among 2,558 non-Hispanic white and Hispanic children across 65 Los Angeles neighborhoods. A series of two-level multilevel models were estimated to examine the independent effects of race, ethnicity, and country of origin on childhood asthma. Lifetime asthma prevalence was reported among 9% of children, with no significant differences between Hispanics and non-Hispanic whites overall. However, in fully adjusted models, Hispanic children of non-Mexican origin reported higher odds of asthma compared to non-Hispanic white children. A protective nativity effect was also observed among children of foreign born mothers compared to US born mothers. Our study provides evidence in support of the heterogeneity of childhood asthma by Hispanic ethnicity and maternal nativity. These findings suggest moving beyond solely considering racial/ethnic classifications which could mask subgroups at increased risk of childhood asthma.

Developing an interactive story for children with asthma.

PubMed

Wyatt, Tami H; Li, Xueping; Huang, Yu; Farmer, Rachel; Reed, Delanna; Burkhart, Patricia V

2013-06-01

Despite advancements in asthma treatment and diagnosis, asthma still remains the number 1 cause for hospitalizations in school-aged children. This usability study aimed to develop a child-friendly interactive narrative, Okay with Asthma v2.0, based on the Biopsychosocial Family Model using feedback from children. This fun and kid-friendly program encourages children to manage their own asthma with the help of peers, families, communities, and health care services. With these support structures, children can identify and avoid triggers, monitor their asthma, manage their condition with medications based on an action plan, and learn to live happily with asthma. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanisms altering airway smooth muscle cell Ca+ homeostasis in two asthma models.

PubMed

Kellner, Julia; Tantzscher, Juliane; Oelmez, Hamza; Edelmann, Martin; Fischer, Rainald; Huber, Rudolf Maria; Bergner, Albrecht

2008-01-01

Asthma is characterized by airway remodeling, altered mucus production and airway smooth muscle cell (ASMC) contraction causing extensive airway narrowing. In particular, alterations of ASMC contractility seem to be of crucial importance. The elevation of the cytoplasmic Ca(2+) concentration is a key event leading to ASMC contraction and changes in the agonist-induced Ca(2+) increase in ASMC have been reported in asthma. The aim of this study was to investigate mechanisms underlying these changes. Murine tracheal smooth muscle cells (MTSMC) from T-bet KO mice and human bronchial smooth muscle cells (HBSMC) incubated with IL-13 and IL-4 served as asthma models. Acetylcholine-induced changes in the cytoplasmic Ca(2+) concentration were recorded using fluorescence microscopy and the expression of Ca(2+) homeostasis regulating proteins was investigated with Western blot analysis. Acetylcholine-induced Ca(2+) transients were elevated in both asthma models. This correlated with an increased Ca(2+) content of the sarcoplasmic reticulum (SR). In MTSMC from T-bet KO mice, the expression of the SR Ca(2+) buffers calreticulin and calsequestrin was higher compared to wild-type mice. In HBSMC incubated with IL-13 or IL-4, the expression of ryanodine receptors, inositol-3-phosphate receptors and sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases 2 was increased compared to HBSMC without incubation with interleukins. The enlarged acetylcholine-induced Ca(2+) transients could be reversed by blocking inositol-3-phosphate receptors. We conclude that in the murine asthma model the SR Ca(2+) buffer capacity is increased, while in the human asthma model the expression of SR Ca(2+) channels is altered. The investigation of the Ca(2+) homeostasis of ASMC has the potential to provide new therapeutical options in asthma. Copyright 2008 S. Karger AG, Basel.

An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen.

PubMed

Norris Reinero, Carol R; Decile, Kendra C; Berghaus, Roy D; Williams, Kurt J; Leutenegger, Christian M; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2004-10-01

Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

Sparse modeling of spatial environmental variables associated with asthma

PubMed Central

Chang, Timothy S.; Gangnon, Ronald E.; Page, C. David; Buckingham, William R.; Tandias, Aman; Cowan, Kelly J.; Tomasallo, Carrie D.; Arndt, Brian G.; Hanrahan, Lawrence P.; Guilbert, Theresa W.

2014-01-01

Geographically distributed environmental factors influence the burden of diseases such as asthma. Our objective was to identify sparse environmental variables associated with asthma diagnosis gathered from a large electronic health record (EHR) dataset while controlling for spatial variation. An EHR dataset from the University of Wisconsin’s Family Medicine, Internal Medicine and Pediatrics Departments was obtained for 199,220 patients aged 5–50 years over a three-year period. Each patient’s home address was geocoded to one of 3,456 geographic census block groups. Over one thousand block group variables were obtained from a commercial database. We developed a Sparse Spatial Environmental Analysis (SASEA). Using this method, the environmental variables were first dimensionally reduced with sparse principal component analysis. Logistic thin plate regression spline modeling was then used to identify block group variables associated with asthma from sparse principal components. The addresses of patients from the EHR dataset were distributed throughout the majority of Wisconsin’s geography. Logistic thin plate regression spline modeling captured spatial variation of asthma. Four sparse principal components identified via model selection consisted of food at home, dog ownership, household size, and disposable income variables. In rural areas, dog ownership and renter occupied housing units from significant sparse principal components were associated with asthma. Our main contribution is the incorporation of sparsity in spatial modeling. SASEA sequentially added sparse principal components to Logistic thin plate regression spline modeling. This method allowed association of geographically distributed environmental factors with asthma using EHR and environmental datasets. SASEA can be applied to other diseases with environmental risk factors. PMID:25533437

Sparse modeling of spatial environmental variables associated with asthma.

PubMed

Chang, Timothy S; Gangnon, Ronald E; David Page, C; Buckingham, William R; Tandias, Aman; Cowan, Kelly J; Tomasallo, Carrie D; Arndt, Brian G; Hanrahan, Lawrence P; Guilbert, Theresa W

2015-02-01

Geographically distributed environmental factors influence the burden of diseases such as asthma. Our objective was to identify sparse environmental variables associated with asthma diagnosis gathered from a large electronic health record (EHR) dataset while controlling for spatial variation. An EHR dataset from the University of Wisconsin's Family Medicine, Internal Medicine and Pediatrics Departments was obtained for 199,220 patients aged 5-50years over a three-year period. Each patient's home address was geocoded to one of 3456 geographic census block groups. Over one thousand block group variables were obtained from a commercial database. We developed a Sparse Spatial Environmental Analysis (SASEA). Using this method, the environmental variables were first dimensionally reduced with sparse principal component analysis. Logistic thin plate regression spline modeling was then used to identify block group variables associated with asthma from sparse principal components. The addresses of patients from the EHR dataset were distributed throughout the majority of Wisconsin's geography. Logistic thin plate regression spline modeling captured spatial variation of asthma. Four sparse principal components identified via model selection consisted of food at home, dog ownership, household size, and disposable income variables. In rural areas, dog ownership and renter occupied housing units from significant sparse principal components were associated with asthma. Our main contribution is the incorporation of sparsity in spatial modeling. SASEA sequentially added sparse principal components to Logistic thin plate regression spline modeling. This method allowed association of geographically distributed environmental factors with asthma using EHR and environmental datasets. SASEA can be applied to other diseases with environmental risk factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Mesenchymal stem cells suppress lung inflammation and airway remodeling in chronic asthma rat model via PI3K/Akt signaling pathway

PubMed Central

Lin, Hai-Yan; Xu, Lei; Xie, Shuan-Shuan; Yu, Fei; Hu, Hai-Yang; Song, Xiao-Lian; Wang, Chang-Hui

2015-01-01

Background: Mesenchymal stem cells (MSCs) came out to attract wide attention and had become one of the hotspots of most diseases’ research in decades. But at present, the mechanisms of how MSCs work on chronic asthma remain undefined. Our study aims at verifying whether MSCs play a role in preventing inflammation and airway remodeling via PI3K/AKT signaling pathway in the chronic asthma rats model. Methods: First, an ovalbumin (OVA)-induced asthma model was built. MSCs were administered to ovalbumin-induced asthma rats. The total cells in a bronchial alveolar lavage fluid (BALF) and inflammatory mediators in BALF and serum were measured. Histological examination of lung tissue was performed to estimate the pathological changes. Additionally, the expression of phosphorylated-Akt (p-Akt) in all groups was measured by western blot and immunohistochemistry (IHC). Results: Compared to normal control group, the degree of airway inflammation and airway remodeling was significantly increased in asthma group. On the contrary, they were obviously inhibited in MSCs transplantation group. Moreover, the expression of p-Akt was increased in lung tissues of asthmatic rats, and suppressed by MSCs transplantation. Conclusion: Our results demonstrated that MSCs transplantation could suppress lung inflammation and airway remodeling via PI3K/Akt signaling pathway in rat asthma model. PMID:26464637

Rodent allergen in Los Angeles inner city homes of children with asthma.

PubMed

Berg, Jill; McConnell, Rob; Milam, Joel; Galvan, Judith; Kotlerman, Jenny; Thorne, Peter; Jones, Craig; Ferdman, Ronald; Eggleston, Peyton; Rand, Cynthia; Lewis, Mary Ann; Peters, John; Richardson, Jean

2008-01-01

Recent studies have examined the presence of mouse allergen in inner city children with asthma. Researchers have found high levels of rodent allergen in homes sampled in the northeast and midwest United States, but there has been considerable variation between cities, and there have been few studies conducted in western states. We evaluated the frequency of rodent sightings and detectable mouse allergen and the housing conditions associated with these outcomes in inner city homes in Los Angeles. Two hundred and two families of school children, ages 6-16 living in inner city neighborhoods, participated in the study. Families were predominantly Latino (94%), and Spanish speaking (92%). At study entry, parents completed a home assessment questionnaire, and staff conducted a home evaluation and collected kitchen dust, which was analyzed for the presence of mouse allergen. Fifty-one percent of homes had detectable allergen in kitchen dust. All 33 families who reported the presence of rodents had detectable allergen in the home and were also more likely to have increased levels of allergen compared to those who did not report rodents. Unwashed dishes or food crumbs, lack of a working vacuum, and a caretaker report of a smoker in the home were all significantly associated with a greater risk of rodent sightings or detectable allergen (P<0.05). Detached homes were significantly more likely to have detectable allergen. The prevalence of allergen is common enough that it may have public health implications for asthmatic children, and detectable allergen was not routinely identified based on rodent sightings. Many of the predictors of rodent allergen are amenable to low-cost interventions that can be integrated with other measures to reduce exposure to indoor allergens.

Association of hospitalizations for asthma with seasonal and pandemic influenza.

PubMed

Gerke, Alicia K; Yang, Ming; Tang, Fan; Foster, Eric D; Cavanaugh, Joseph E; Polgreen, Philip M

2014-01-01

Although influenza has been associated with asthma exacerbations, it is not clear the extent to which this association affects health care use in the United States. The first goal of this project was to determine whether, and to what extent, the incidence of asthma hospitalizations is associated with seasonal variation in influenza. Second, we used influenza trends (2000-2008) to help predict asthma admissions during the 2009 H1N1 influenza pandemic. We identified all hospitalizations between 1998 and 2008 in the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project during which a primary diagnosis of asthma was recorded. Separately, we identified all hospitalizations during which a diagnosis of influenza was recorded. We performed time series regression analyses to investigate the association of monthly asthma admissions with influenza incidence. Finally, we applied these time series regression models using 1998-2008 data, to forecast monthly asthma admissions during the 2009 influenza pandemic. Based on time series regression models, a strong, significant association exists between concurrent influenza activity and incidence of asthma hospitalizations (P-value < 0.0001). Use of influenza data to predict asthma admissions during the 2009 H1N1 pandemic improved the mean squared prediction error by 60.2%. Influenza activity in the population is significantly associated with asthma hospitalizations in the United States, and this association can be exploited to more accurately forecast asthma admissions. Our results suggest that improvements in influenza surveillance, prevention and treatment may decrease hospitalizations of asthma patients. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Characteristics of Perimenstrual Asthma and Its Relation to Asthma Severity and Control

PubMed Central

Rao, Chitra K.; Moore, Charity G.; Bleecker, Eugene; Busse, William W.; Calhoun, William; Castro, Mario; Chung, Kian Fan; Erzurum, Serpil C.; Israel, Elliot; Curran-Everett, Douglas

2013-01-01

Background: Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control. Methods: Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control. Results: Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization. Conclusions: PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype. PMID:23632943

Seasonal asthma in Melbourne, Australia, and some observations on the occurrence of thunderstorm asthma and its predictability

PubMed Central

Sutherland, Michael F.; Johnston, Fay H.; Lampugnani, Edwin R.; McCarthy, Michael A.; Jacobs, Stephanie J.; Pezza, Alexandre B.; Newbigin, Edward J.

2018-01-01

We examine the seasonality of asthma-related hospital admissions in Melbourne, Australia, in particular the contribution and predictability of episodic thunderstorm asthma. Using a time-series ecological approach based on asthma admissions to Melbourne metropolitan hospitals, we identified seasonal peaks in asthma admissions that were centred in late February, June and mid-November. These peaks were most likely due to the return to school, winter viral infections and seasonal allergies, respectively. We performed non-linear statistical regression to predict daily admission rates as functions of the seasonal cycle, weather conditions, reported thunderstorms, pollen counts and air quality. Important predictor variables were the seasonal cycle and mean relative humidity in the preceding two weeks, with higher humidity associated with higher asthma admissions. Although various attempts were made to model asthma admissions, none of the models explained substantially more variation above that associated with the annual cycle. We also identified a list of high asthma admissions days (HAADs). Most HAADs fell in the late-February return-to-school peak and the November allergy peak, with the latter containing the greatest number of daily admissions. Many HAADs in the spring allergy peak may represent episodes of thunderstorm asthma, as they were associated with rainfall, thunderstorms, high ambient grass pollen levels and high humidity, a finding that suggests thunderstorm asthma is a recurrent phenomenon in Melbourne that occurs roughly once per five years. The rarity of thunderstorm asthma events makes prediction challenging, underscoring the importance of maintaining high standards of asthma management, both for patients and health professionals, especially during late spring and early summer. PMID:29649224

Urbanization factors associated with childhood asthma and prematurity: a population-based analysis aged from 0 to 5 years in Taiwan by using Cox regression within a hospital cluster model.

PubMed

Lin, Sheng-Chieh; Lin, Hui-Wen

2015-04-01

Childhood asthma and premature birth are both common; however, no studies have reported urbanization association between asthma and prematurity and the duration of prematurity affect asthma development. We use Taiwan Longitudinal Health Insurance Database (LHID) to explore association between asthma and prematurity among children by using a population-based analysis. This is a retrospective cohort study with registration data derived from Taiwan LHID. We evaluated prematurely born infants and children aged <5 years (n = 532) and age-matched control patients (n = 60505) using Cox proportional hazard regression analysis within a hospital cluster model. Of the 61 037 examinees, 14 012 experienced asthma during the 5-year follow-up, including 161 (72.26 per 1000 person-years) infants and children born prematurely and 13 851 (40.27 per 1000 person-years) controls. The hazard ratio for asthma during 5-year follow-up period was 1.95 (95% confidence interval = 1.67-2.28) among children born prematurely. Boys born prematurely aged 0-2 years were associated with higher asthma rates compared with girls in non-premature and premature groups. Living in urban areas, those born prematurely were associated with higher rates of asthma compared with non-prematurity. Those born prematurely lived in northern region had higher asthma hazard ratio than other regions. Our analyses indicated that sex, age, urbanization level, and geographic region are significantly associated with prematurity and asthma. Based on cumulative asthma-free survival curve generated using the Kaplan-Meier method, infants born prematurely should be closely monitored to see if they would develop asthma until the age of 6 years.

Animal models of asthma: utility and limitations.

PubMed

Aun, Marcelo Vivolo; Bonamichi-Santos, Rafael; Arantes-Costa, Fernanda Magalhães; Kalil, Jorge; Giavina-Bianchi, Pedro

2017-01-01

Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila , rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes of allergen administration.

A simulation model of building intervention impacts on indoor environmental quality, pediatric asthma, and costs

PubMed Central

Fabian, Maria Patricia; Adamkiewicz, Gary; Stout, Natasha Kay; Sandel, Megan; Levy, Jonathan Ian

2013-01-01

Background Although indoor environmental conditions can affect pediatric asthmatics, few studies have characterized the impact of building interventions on asthma-related outcomes. Simulation models can evaluate such complex systems but have not been applied in this context. Objective To evaluate the impacts of building interventions on indoor environmental quality and pediatric asthma healthcare utilization, and to conduct cost comparisons between intervention and healthcare costs, and energy savings. Methods We applied our previously developed discrete event simulation model (DEM) to simulate the effect of environmental factors, medication compliance, seasonality, and medical history on: 1) pollutant concentrations indoors, and 2) asthma outcomes in low-income multi-family housing. We estimated healthcare utilization and costs at baseline and subsequent to interventions, and then compared healthcare costs to energy savings and intervention costs. Results Interventions such as integrated pest management and repairing kitchen exhaust fans led to 7–12% reductions in serious asthma events with 1–3 year payback periods. Weatherization efforts targeted solely towards tightening a building envelope led to 20% more serious asthma events, but bundling with repairing kitchen exhaust fans and eliminating indoor sources (e.g. gas stoves or smokers) mitigated this impact. Conclusion Our pediatric asthma model provides a tool to prioritize individual and bundled building interventions based on their impact on health and cost, and highlighting the tradeoffs between weatherization, indoor air quality, and health. Our work bridges the gap between clinical and environmental health sciences by increasing physicians’ understanding of the impact that home environmental changes can have on their patients’ asthma. PMID:23910689

Methyl methacrylate and respiratory sensitization: A Critical review

PubMed Central

Borak, Jonathan; Fields, Cheryl; Andrews, Larry S; Pemberton, Mark A

2011-01-01

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer. PMID:21401327

Predictive value of serum sST2 in preschool wheezers for development of asthma with high FeNO.

PubMed

Ketelaar, M E; van de Kant, K D; Dijk, F N; Klaassen, E M; Grotenboer, N S; Nawijn, M C; Dompeling, E; Koppelman, G H

2017-11-01

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 (IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Estimating Wisconsin asthma prevalence using clinical electronic health records and public health data.

PubMed

Tomasallo, Carrie D; Hanrahan, Lawrence P; Tandias, Aman; Chang, Timothy S; Cowan, Kelly J; Guilbert, Theresa W

2014-01-01

We compared a statewide telephone health survey with electronic health record (EHR) data from a large Wisconsin health system to estimate asthma prevalence in Wisconsin. We developed frequency tables and logistic regression models using Wisconsin Behavioral Risk Factor Surveillance System and University of Wisconsin primary care clinic data. We compared adjusted odds ratios (AORs) from each model. Between 2007 and 2009, the EHR database contained 376,000 patients (30,000 with asthma), and 23,000 (1850 with asthma) responded to the Behavioral Risk Factor Surveillance System telephone survey. AORs for asthma were similar in magnitude and direction for the majority of covariates, including gender, age, and race/ethnicity, between survey and EHR models. The EHR data had greater statistical power to detect associations than did survey data, especially in pediatric and ethnic populations, because of larger sample sizes. EHRs can be used to estimate asthma prevalence in Wisconsin adults and children. EHR data may improve public health chronic disease surveillance using high-quality data at the local level to better identify areas of disparity and risk factors and guide education and health care interventions.

Indoor Environmental Exposures for Children with Asthma Enrolled in the HEAL Study, Post-Katrina New Orleans

PubMed Central

Chulada, Patricia C.; Kennedy, Suzanne; White, LuAnn; Wildfire, Jeremy; Cohn, Richard D.; Mitchell, Herman; Thornton, Eleanor; El-Dahr, Jane; Mvula, Mosanda M.; Sterling, Yvonne; Martin, William J.; Stephens, Kevin U.; Lichtveld, Maureen

2012-01-01

Background: Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma. Objectives: The goal of the Head-off Environmental Asthma in Louisiana (HEAL) study was to characterize post-Katrina exposures to mold and allergens in children with asthma. Methods: The homes of 182 children with asthma in New Orleans and surrounding parishes were evaluated by visual inspection, temperature and moisture measurements, and air and dust sampling. Air was collected using vacuum-pump spore traps and analyzed for > 30 mold taxa using bright field microscopy. Dust was collected from the children’s beds and bedroom floors and analyzed for mouse (Mus m 1), dust mite (Der p 1), cockroach (Bla g 1), and mold (Alternaria mix) allergens using ELISA. Results: More than half (62%) of the children were living in homes that had been damaged by rain, flooding, or both. Geometric mean indoor and outdoor airborne mold levels were 501 and 3,958 spores/m3, respectively. Alternaria antigen was detected in dust from 98% of homes, with 58% having concentrations > 10 µg/g. Mus m 1, Der p 1, and Bla g 1 were detected in 60%, 35%, and 20% of homes, respectively, at low mean concentrations. Conclusions: Except for Alternaria antigen in dust, concentrations of airborne mold (ratio of indoor to outdoor mold) and dust allergens in the homes of HEAL children were lower than measurements found in other studies, possibly because of extensive post-Katrina mold remediation and renovations, or because children moved into cleaner homes upon returning to New Orleans. PMID:22894816

Indoor environmental exposures for children with asthma enrolled in the HEAL study, post-Katrina New Orleans.

PubMed

Grimsley, L Faye; Chulada, Patricia C; Kennedy, Suzanne; White, LuAnn; Wildfire, Jeremy; Cohn, Richard D; Mitchell, Herman; Thornton, Eleanor; El-Dahr, Jane; Mvula, Mosanda M; Sterling, Yvonne; Martin, William J; Stephens, Kevin U; Lichtveld, Maureen

2012-11-01

Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma. The goal of the Head-off Environmental Asthma in Louisiana (HEAL) study was to characterize post-Katrina exposures to mold and allergens in children with asthma. The homes of 182 children with asthma in New Orleans and surrounding parishes were evaluated by visual inspection, temperature and moisture measurements, and air and dust sampling. Air was collected using vacuum-pump spore traps and analyzed for > 30 mold taxa using bright field microscopy. Dust was collected from the children's beds and bedroom floors and analyzed for mouse (Mus m 1), dust mite (Der p 1), cockroach (Bla g 1), and mold (Alternaria mix) allergens using ELISA. More than half (62%) of the children were living in homes that had been damaged by rain, flooding, or both. Geometric mean indoor and outdoor airborne mold levels were 501 and 3,958 spores/m3, respectively. Alternaria antigen was detected in dust from 98% of homes, with 58% having concentrations > 10 µg/g. Mus m 1, Der p 1, and Bla g 1 were detected in 60%, 35%, and 20% of homes, respectively, at low mean concentrations. Except for Alternaria antigen in dust, concentrations of airborne mold (ratio of indoor to outdoor mold) and dust allergens in the homes of HEAL children were lower than measurements found in other studies, possibly because of extensive post-Katrina mold remediation and renovations, or because children moved into cleaner homes upon returning to New Orleans.

Integration of Airborne Aerosol Prediction Systems and Vegetation Phenology to Track Pollen for Asthma Alerts in Public Health Decision Support Systems

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey C.; Sprigg, William A.; Huete, Alfredo; Pejanovic, Goran; Nickovic,Slobodan; Ponce-Campos, Guillermo; Krapfl, Heide; Budge, Amy; Zelicoff, Alan; VandeWater, Peter K.;

The Chronic Care Model: A Collaborative Approach to Preventing and Treating Asthma in Infants and Young Children

ERIC Educational Resources Information Center

Wessel, Lois; Spain, Jacqueline

2005-01-01

The authors that a collaborative approach between parents and professionals is the best way to care for a young child with asthma. They use Ed Wagner's transdisciplinary 1998 Chronic Care Model as their preferred method for collaboration. More than 5 million children in the U.S. are currently affected by asthma, and a growing body of evidence…

Turmeric (Curcuma longa) attenuates food allergy symptoms by regulating type 1/type 2 helper T cells (Th1/Th2) balance in a mouse model of food allergy.

PubMed

Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Choi, Dae Woon; Kwon, Da-Ae; Bae, Min-Jung; Sung, Ki-Seung; Shon, Dong-Hwa

2015-12-04

Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies. Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA. Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice. Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Exploration and research of community management model for asthmatic children].

PubMed

Li, Jingpeng; Wei, Hong; Li, Xuejun; Wang, Mengmeng; Wang, Genxiang; Zhao, Shunying

2014-05-01

To study the efficacy of community management model of bronchial asthma in children. Through community outreach and clinic, 120 cases of children with asthma were enrolled from the 11 000 children aged 0 to 14 in Zhanlanlu area, and a community management model of asthma was established according to the Global Initiative for Asthma requirements combined with the actual situation of the community, both physicians and patients participated in case identification, file creation, and long-term standardized management. Through repeated medical education, the telephone hotline and interactive network of asthma among physicians, children and parents, a physician-patient relationship was established. The data of standardized medication, scheduled re-visit to the hospital, frequency of asthma attacks, antibiotic use, medical expenses, the loss of parents work hours etc. before and after the implementation of community management model were analyzed and compared. After implementation of community management model, the use of systemic corticosteroids (19.4%), oral medication (31.6%) was significantly lower than those before implementation (68.3% and 90.0%) (χ(2) = 51.9, 41.1, P < 0.01), use of inhaled corticosteroids (76.5%) and oral leukotriene receptor antagonist (79.6%) was significantly higher compared with control and before management level (10.0%), χ(2) = 106.0, P < 0.01. The days of attacks of asthma (4.6 ± 2.3), the use of antibiotics (16.2 ± 6.1), (5.7 ± 2.9) and the cost of treatment significantly decreased. In 16 cases (13.3%) two-way referral was applied. In this study, the dropout rate was 18.3%, by telephone and network supervision of lost cases, re-education, made some children return to management, eventually the dropout rate was 9.2%. Enrollment of children with bronchial asthma into community management model made the children adhere to the management regularly and a standardized management was achieved.

Improving asthma management among African-American children via a community health worker model: findings from a Chicago-based pilot intervention.

PubMed

Margellos-Anast, Helen; Gutierrez, Melissa A; Whitman, Steven

2012-05-01

Asthma affects 25-30% of children living in certain disadvantaged Chicago neighborhoods, a rate twice the national prevalence (13%). Children living in poor, minority communities tend to rely heavily on the emergency department (ED) for asthma care and are unlikely to be properly medicated or educated on asthma self-management. A pilot project implemented and evaluated a community health worker (CHW) model for its effectiveness in reducing asthma morbidity and improving the quality of life among African-American children living in disadvantaged Chicago neighborhoods. Trained CHWs from targeted communities provided individualized asthma education during three to four home visits over 6 months. The CHWs also served as liaisons between families and the medical system. Seventy children were enrolled into the pilot phase between 15 November 2004 and 15 July 2005, of which 96% were insured by Medicaid and 54% lived with a smoker. Prior to starting, the study was approved by an institutional review board. Data on 50 children (71.4%) who completed the entire 12-month evaluation phase were analyzed using a before and after study design. Findings indicate improved asthma control. Specifically, symptom frequency was reduced by 35% and urgent health resource utilization by 75% between the pre- and post-intervention periods. Parental quality of life also improved by a level that was both clinically and statistically significant. Other important outcomes included improved asthma-related knowledge, decreased exposure to asthma triggers, and improved medical management. The intervention was also shown to be cost-effective, resulting in an estimated $5.58 saved per dollar spent on the intervention. Findings suggest that individualized asthma education provided by a trained, culturally competent CHW is effective in improving asthma management among poorly controlled, inner-city children. Further studies are needed to affirm the findings and assess the model's generalizability.

Asthma exacerbation and proximity of residence to major roads: a population-based matched case-control study among the pediatric Medicaid population in Detroit, Michigan

PubMed Central

2011-01-01

Background The relationship between asthma and traffic-related pollutants has received considerable attention. The use of individual-level exposure measures, such as residence location or proximity to emission sources, may avoid ecological biases. Method This study focused on the pediatric Medicaid population in Detroit, MI, a high-risk population for asthma-related events. A population-based matched case-control analysis was used to investigate associations between acute asthma outcomes and proximity of residence to major roads, including freeways. Asthma cases were identified as all children who made at least one asthma claim, including inpatient and emergency department visits, during the three-year study period, 2004-06. Individually matched controls were randomly selected from the rest of the Medicaid population on the basis of non-respiratory related illness. We used conditional logistic regression with distance as both categorical and continuous variables, and examined non-linear relationships with distance using polynomial splines. The conditional logistic regression models were then extended by considering multiple asthma states (based on the frequency of acute asthma outcomes) using polychotomous conditional logistic regression. Results Asthma events were associated with proximity to primary roads with an odds ratio of 0.97 (95% CI: 0.94, 0.99) for a 1 km increase in distance using conditional logistic regression, implying that asthma events are less likely as the distance between the residence and a primary road increases. Similar relationships and effect sizes were found using polychotomous conditional logistic regression. Another plausible exposure metric, a reduced form response surface model that represents atmospheric dispersion of pollutants from roads, was not associated under that exposure model. Conclusions There is moderately strong evidence of elevated risk of asthma close to major roads based on the results obtained in this population-based matched case-control study. PMID:21513554

Impact of childhood asthma on growth trajectories in early adolescence: Findings from the Childhood Asthma Prevention Study (CAPS).

PubMed

Movin, Maria; Garden, Frances L; Protudjer, Jennifer L P; Ullemar, Vilhelmina; Svensdotter, Frida; Andersson, David; Kruse, Andreas; Cowell, Chris T; Toelle, Brett G; Marks, Guy B; Almqvist, Catarina

2017-04-01

Understanding the associations between childhood asthma and growth in early adolescence by accounting for the heterogeneity of growth during puberty has been largely unexplored. The objective was to identify sex-specific classes of growth trajectories during early adolescence, using a method which takes the heterogeneity of growth into account and to evaluate the association between childhood asthma and different classes of growth trajectories in adolescence. Our longitudinal study included participants with a family history of asthma born during 1997-1999 in Sydney, Australia. Hence, all participants were at high risk for asthma. Asthma status was ascertained at 8 years of age using data from questionnaires and lung function tests. Growth trajectories between 11 and 14 years of age were classified using a latent basis growth mixture model. Multinomial regression analyses were used to evaluate the association between asthma and the categorized classes of growth trajectories. In total, 316 participants (51.6% boys), representing 51.3% of the entire cohort, were included. Sex-specific classes of growth trajectories were defined. Among boys, asthma was not associated with the classes of growth trajectories. Girls with asthma were more likely than girls without asthma to belong to a class with later growth (OR: 3.79, 95% CI: 1.33, 10.84). Excluding participants using inhaled corticosteroids or adjusting for confounders did not significantly change the results for either sex. We identified sex-specific heterogeneous classes of growth using growth mixture modelling. Associations between childhood asthma and different classes of growth trajectories were found for girls only. © 2016 Asian Pacific Society of Respirology.

Predictors of perceived asthma control among patients managed in primary care clinics.

PubMed

Eilayyan, Owis; Gogovor, Amede; Mayo, Nancy; Ernst, Pierre; Ahmed, Sara

2015-01-01

To estimate the extent to which symptom status, physical activity, beliefs about medications, self-efficacy, emotional status, and healthcare utilization predict perceived asthma control over a period of 16 months among a primary care population. The current study is a secondary analysis of data from a longitudinal study that examined health outcomes of asthma among participants recruited from primary care clinics. Path analysis, based on the Wilson and Cleary and International Classification of Functioning, Disability and Health frameworks, was used to estimate the predictors of perceived asthma control. The path analysis identified initial perceived asthma control asthma (β = 0.43, p < 0.0001), symptoms (β = 0.35, p < 0.0001), physical activity (β = 0.27, p < 0.0001), and self-efficacy (β = 0.29, p < 0.0001) as significant predictors of perceived asthma control (total effects, i.e., direct and indirect), while emotional status (β = 0.08, p = 0.03) was a significant indirect predictor through physical activity. The model explained 24 % of the variance of perceived asthma control. Overall, the model fits the data well (χ (2) = 6.65, df = 6, p value = 0.35, root-mean-square error of approximation = 0.02, Comparative Fit Index = 0.999, and weighted root-mean-square residual = 0.27). Initial perceived asthma control, current symptoms status, physical activity, and self-efficacy can be used to identify individuals likely to have good perceived asthma control in the future. Emotional status also has an impact on perceived asthma control mediated through physical activity and should be considered when planning patient management. Identifying these predictors is important to help the care team tailor interventions that will allow individuals to optimally manage their asthma, to prevent exacerbations, to prevent other respiratory-related chronic disease, and to maximize quality of life.

Relationship of self-reported asthma severity and urgent health care utilization to psychological sequelae of the September 11, 2001 terrorist attacks on the World Trade Center among New York City area residents.

PubMed

Fagan, Joanne; Galea, Sandro; Ahern, Jennifer; Bonner, Sebastian; Vlahov, David

2003-01-01

Posttraumatic psychological stress may be associated with increases in somatic illness, including asthma, but the impact of the psychological sequelae of the September 11, 2001 terrorist attacks on physical illness has not been well documented. The authors assessed the relationship between the psychological sequelae of the attacks and asthma symptom severity and the utilization of urgent health care services for asthma since September 11. The authors performed a random digit dial telephone survey of adults in the New York City (NYC) metropolitan area 6 to 9 months after September 11, 2001. Two thousand seven hundred fifty-five demographically representative adults including 364 asthmatics were recruited. The authors assessed self-reported asthma symptom severity, emergency room (ER) visits, and unscheduled physician office visits for asthma since September 11. After adjustment for asthma measures before September 11, demographics, and event exposure in multivariate models posttraumatic stress disorder (PTSD) were a significant predictor of self-reported moderate-to-severe asthma symptoms (OR = 3.4; CI = 1.2-9.4), seeking care for asthma at an ER since September 11 (OR = 6.6; CI = 1.6-28.0), and unscheduled physician visits for asthma since September 11 (OR = 3.6; CI = 1.1-11.5). The number of PTSD symptoms was also significantly related to moderate-to-severe asthma symptoms and unscheduled physician visits since September 11. Neither a panic attack on September 11 nor depression since September 11 was an independent predictor of asthma severity or utilization in multivariate models after September 11. PTSD related to the September 11 terrorist attacks contributed to symptom severity and the utilization of urgent health care services among asthmatics in the NYC metropolitan area.

Association between Allergic Rhinitis and Asthma Control in Peruvian School Children: A Cross-Sectional Study

PubMed Central

Uceda, Mónica; Ziegler, Otto; Lindo, Felipe; Herrera-Pérez, Eder

2013-01-01

Background. Asthma and allergic rhinitis are highly prevalent conditions that cause major illness worldwide. This study aimed to assess the association between allergic rhinitis and asthma control in Peruvian school children. Methods. A cross-sectional study was conducted among 256 children with asthma recruited in 5 schools from Lima and Callao cities. The outcome was asthma control assessed by the asthma control test. A score test for trend of odds was used to evaluate the association between allergic rhinitis severity and the prevalence of inadequate asthma control. A generalized linear regression model was used to estimate the adjusted prevalence ratios of inadequate asthma control. Results. Allergic rhinitis was present in 66.4% of the population with asthma. The trend analysis showed a positive association between allergic rhinitis and the probability of inadequate asthma control (P < 0.001). It was associated with an increased prevalence of inadequate asthma control, with adjusted prevalence ratios of 1.53 (95% confidence interval: 1.19−1.98). Conclusion. This study indicates that allergic rhinitis is associated with an inadequate level of asthma control, giving support to the recommendation of evaluating rhinitis to improve asthma control in children. PMID:23984414

Oxidative stress biomarkers and asthma characteristics in adults of the EGEA study.

PubMed

Andrianjafimasy, Miora; Zerimech, Farid; Akiki, Zeina; Huyvaert, Helene; Le Moual, Nicole; Siroux, Valérie; Matran, Régis; Dumas, Orianne; Nadif, Rachel

2017-12-01

Asthma is an oxidative stress related disease, but associations with asthma outcomes are poorly studied in adults. We aimed to study the associations between several biomarkers related to oxidative stress and various asthma outcomes.Cross-sectional analyses were conducted in 1388 adults (mean age 43 years, 44% with asthma) from the Epidemiological Study of the Genetics and Environment of Asthma (EGEA2). Three blood antioxidant enzyme activities (biomarkers of response to oxidative stress) and exhaled breath condensate 8-isoprostanes and plasma fluorescent oxidation products (FlOPs) levels (two biomarkers of damage) were measured. Associations between biomarkers and 1) ever asthma and 2) asthma attacks, asthma control and lung function in participants with asthma were evaluated using regression models adjusted for age, sex and smoking.Biomarkers of response were unrelated to asthma outcomes. Higher 8-isoprostane levels were significantly associated with ever asthma (odds ratio for one interquartile range increase 1.28 (95% CI 1.06-1.67). Among participants with asthma, 8-isoprostane levels were negatively associated with adult-onset asthma (0.63, 0.41-0.97) and FlOPs levels were positively associated with asthma attacks (1.33, 1.07-1.65), poor asthma control (1.30, 1.02-1.66) and poor lung function (1.34, 1.04-1.74).Our results suggest that 8-isoprostanes are involved in childhood-onset asthma and FlOPs are linked to asthma expression. Copyright ©ERS 2017.

Effects of temperature variation between neighbouring days on daily hospital visits for childhood asthma: a time-series analysis.

PubMed

Li, K; Ni, H; Yang, Z; Wang, Y; Ding, S; Wen, L; Yang, H; Cheng, J; Su, H

2016-07-01

To identify the relationship between temperature variation between neighbouring days (TVN) and hospital visits for childhood asthma in age- and sex-specific groups. An ecological design was used to explore the effect of TVN on hospital visits for childhood asthma. A Poisson generalised linear regression model combined with a distributed lag non-linear model was used to analyse the association between TVN and hospital visits for childhood asthma. All hospital visits for childhood asthma from June 2010 to July 2013 were included (n = 17,022). Daily climate data were obtained from Hefei Meteorological Bureau. A significant correlation was found between TVN and hospital visits for childhood asthma in age- and sex-specific groups. For different gender groups, the effect of TVN on childhood asthma was the greatest at 3 and 5 days lag for males and females. For different age groups, the effect of TVN on childhood asthma was the greatest at 1 and 5 days lag for 0-4 years and 5-14 years children, respectively. A 1 °C increase in TVN was associated with a 4.2% (95% confidence interval 0.9-7.6%) increase in hospital visits for childhood asthma. TVN is associated with hospital visits for childhood asthma. Once the temperature change rapidly, guardians will be urged to pay more attention to their children's health, which may reduce the morbidity of childhood asthma. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Ambient air pollution, traffic noise and adult asthma prevalence: a BioSHaRE approach.

PubMed

Cai, Yutong; Zijlema, Wilma L; Doiron, Dany; Blangiardo, Marta; Burton, Paul R; Fortier, Isabel; Gaye, Amadou; Gulliver, John; de Hoogh, Kees; Hveem, Kristian; Mbatchou, Stéphane; Morley, David W; Stolk, Ronald P; Elliott, Paul; Hansell, Anna L; Hodgson, Susan

2017-01-01

We investigated the effects of both ambient air pollution and traffic noise on adult asthma prevalence, using harmonised data from three European cohort studies established in 2006-2013 (HUNT3, Lifelines and UK Biobank).Residential exposures to ambient air pollution (particulate matter with aerodynamic diameter ≤10 µm (PM 10 ) and nitrogen dioxide (NO 2 )) were estimated by a pan-European Land Use Regression model for 2007. Traffic noise for 2009 was modelled at home addresses by adapting a standardised noise assessment framework (CNOSSOS-EU). A cross-sectional analysis of 646 731 participants aged ≥20 years was undertaken using DataSHIELD to pool data for individual-level analysis via a "compute to the data" approach. Multivariate logistic regression models were fitted to assess the effects of each exposure on lifetime and current asthma prevalence.PM 10 or NO 2 higher by 10 µg·m -3 was associated with 12.8% (95% CI 9.5-16.3%) and 1.9% (95% CI 1.1-2.8%) higher lifetime asthma prevalence, respectively, independent of confounders. Effects were larger in those aged ≥50 years, ever-smokers and less educated. Noise exposure was not significantly associated with asthma prevalence.This study suggests that long-term ambient PM 10 exposure is associated with asthma prevalence in western European adults. Traffic noise is not associated with asthma prevalence, but its potential to impact on asthma exacerbations needs further investigation. Copyright ©ERS 2017.

The impact of the parental illness representation on disease management in childhood asthma.

PubMed

Yoos, H Lorrie; Kitzman, Harriet; Henderson, Charles; McMullen, Ann; Sidora-Arcoleo, Kimberly; Halterman, Jill S; Anson, Elizabeth

2007-01-01

Despite significant advances in treatment modalities, morbidity due to childhood asthma has continued to increase, particularly for poor and minority children. To describe the parental illness representation of asthma in juxtaposition to the professional model of asthma and to evaluate the impact of that illness representation on the adequacy of the child's medication regimen. Parents (n = 228) of children with asthma were interviewed regarding illness beliefs using a semistructured interview. The impact of background characteristics, parental beliefs, the child's symptom interpretation, and the parent-healthcare provider (HCP) relationship on the adequacy of the child's medication regimen were evaluated. The parental and professional models of asthma differ markedly. Demographic risk factors (p = .005), low parental education (p < .0001), inaccurate symptom evaluation by the child (p = .02), and a poor parent-HCP relationship (p < .0001) had a negative effect on the parental illness representation. A parental illness representation concordant with the professional model of asthma (p = .05) and more formal asthma education (p = .02) had a direct positive effect on the medication regimen. Demographic risk factors (p = .006) and informal advice-seeking (p = .0003) had a negative impact on the regimen. The parental illness representation mediated the impact of demographic risk factors (p = .10), parental education (p =.07), and the parent-HCP relationship (p = .06) on the regimen. Parents and HCPs may come to the clinical encounter with markedly different illness representations. Establishing a partnership with parents by eliciting and acknowledging parental beliefs is an important component of improving disease management.

Nelumbo nucifera leaves extracts inhibit mouse airway smooth muscle contraction.

PubMed

Yang, Xiao; Xue, Lu; Zhao, Qingyang; Cai, Congli; Liu, Qing-Hua; Shen, Jinhua

2017-03-20

Alkaloids extracted from lotus leaves (AELL) can relax vascular smooth muscle. However, whether AELL has a similar relaxant role on airway smooth muscle (ASM) remains unknown. This study aimed to explore the relaxant property of AELL on ASM and the underlying mechanism. Alkaloids were extracted from dried lotus leaves using the high temperature rotary evaporation extraction method. The effects of AELL on mouse ASM tension were studied using force measuring and patch-clamp techniques. It was found that AELL inhibited the high K + or acetylcholine chloride (ACh)-induced precontraction of mouse tracheal rings by 64.8 ± 2.9%, or 48.8 ± 4.7%, respectively. The inhibition was statistically significant and performed in a dose-dependent manner. Furthermore, AELL-induced smooth muscle relaxation was partially mediated by blocking voltage-dependent Ca 2+ channels (VDCC) and non-selective cation channels (NSCC). AELL, which plays a relaxant role in ASM, might be a new complementary treatment to treat abnormal contractions of the trachea and asthma.

Stem cells in animal asthma models: a systematic review.

PubMed

Srour, Nadim; Thébaud, Bernard

2014-12-01

Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Single-tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts.

PubMed

Kulis, Mike; Li, Yifan; Lane, Hannah; Pons, Laurent; Burks, Wesley

2011-01-01

Allergic reactions to tree nuts are often severe and are outgrown in less than 10% of diagnosed patients. To determine whether treatment of underlying tree nut sensitization will prevent allergic reactions to cross-reacting tree nuts and to determine the effects of single-tree nut immunotherapy on true multi-tree nut sensitization. Cross-reactivity model: Cashew-sensitized mice underwent immunotherapy with cashew and were subsequently challenged with cashew and pistachio. Multisensitization model: Cashew plus walnut-sensitized mice were treated with cashew alone, walnut alone, or both cashew and walnut and then underwent challenges to cashew and walnut. Challenges were assessed on the basis of symptoms, changes in body temperature, and mouse mast cell protease-1 release. In the cross-reactivity model, cashew immunotherapy completely prevented allergic reactions on challenges with cashew or the cross-reactive pistachio. In the multisensitization model, mice with cashew plus walnut allergy were significantly protected from anaphylactic reactions on cashew challenge in both the cashew-alone and walnut-alone immunotherapy groups. Results from the walnut challenge demonstrated significantly decreased allergic responses in the walnut immunotherapy group, whereas mice in the cashew immunotherapy group experienced significantly lower symptoms. In the cross-reactivity model, immunotherapy effectively decreased IL-4 and IL-5 production and increased IL-12 relative to placebo while also inducing a 5-fold increase in specific IgG(1). Single-tree nut immunotherapy can effectively decrease allergic responses in both the cross-reactivity and multisensitization mouse models. Further studies are needed to determine which single-tree nut immunotherapies will be most effective for specific multi-tree nut allergy profiles. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

PubMed

Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

2017-11-01

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Predicting phenotypes of asthma and eczema with machine learning

PubMed Central

2014-01-01

Background There is increasing recognition that asthma and eczema are heterogeneous diseases. We investigated the predictive ability of a spectrum of machine learning methods to disambiguate clinical sub-groups of asthma, wheeze and eczema, using a large heterogeneous set of attributes in an unselected population. The aim was to identify to what extent such heterogeneous information can be combined to reveal specific clinical manifestations. Methods The study population comprised a cross-sectional sample of adults, and included representatives of the general population enriched by subjects with asthma. Linear and non-linear machine learning methods, from logistic regression to random forests, were fit on a large attribute set including demographic, clinical and laboratory features, genetic profiles and environmental exposures. Outcome of interest were asthma, wheeze and eczema encoded by different operational definitions. Model validation was performed via bootstrapping. Results The study population included 554 adults, 42% male, 38% previous or current smokers. Proportion of asthma, wheeze, and eczema diagnoses was 16.7%, 12.3%, and 21.7%, respectively. Models were fit on 223 non-genetic variables plus 215 single nucleotide polymorphisms. In general, non-linear models achieved higher sensitivity and specificity than other methods, especially for asthma and wheeze, less for eczema, with areas under receiver operating characteristic curve of 84%, 76% and 64%, respectively. Our findings confirm that allergen sensitisation and lung function characterise asthma better in combination than separately. The predictive ability of genetic markers alone is limited. For eczema, new predictors such as bio-impedance were discovered. Conclusions More usefully-complex modelling is the key to a better understanding of disease mechanisms and personalised healthcare: further advances are likely with the incorporation of more factors/attributes and longitudinal measures. PMID:25077568

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models.

PubMed

Liu, Lu; Wang, Lin-Peng; He, Shan; Ma, Yan

2018-05-01

Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of IgE antibodies by B cells and a decrease of the interferon-γ/interleukin-4 (Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine (CM) research on the mechanisms and effificacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the PubMed and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specifific immunoglobulin E, inflflammatory cell infifiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.

Childhood-Onset Asthma in Smokers. Association between CT Measures of Airway Size, Lung Function, and Chronic Airflow Obstruction

PubMed Central

Hardin, Megan E.; Come, Carolyn E.; San José Estépar, Raúl; Ross, James C.; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K.; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K.; Crapo, James D.; Lynch, David A.; Make, Barry; Barr, R. Graham; Hersh, Craig P.; Washko, George R.

2014-01-01

Rationale and Objectives: Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. Methods: We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Measurements and Main Results: Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. Conclusion: In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764). PMID:25296268

Childhood-onset asthma in smokers. association between CT measures of airway size, lung function, and chronic airflow obstruction.

PubMed

Diaz, Alejandro A; Hardin, Megan E; Come, Carolyn E; San José Estépar, Raúl; Ross, James C; Kurugol, Sila; Okajima, Yuka; Han, MeiLan K; Kim, Victor; Ramsdell, Joe; Silverman, Edwin K; Crapo, James D; Lynch, David A; Make, Barry; Barr, R Graham; Hersh, Craig P; Washko, George R

2014-11-01

Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Guinea pig models of asthma.

PubMed

McGovern, Alice E; Mazzone, Stuart B

2014-12-01

Described in this unit are methods for establishing guinea pig models of asthma. Sufficient detail is provided to enable investigators to study bronchoconstriction, cough, airway hyperresponsiveness, inflammation, and remodeling. Copyright © 2014 John Wiley & Sons, Inc.

Modeling asthma: Pitfalls, promises, and the road ahead.

PubMed

Rosenberg, Helene F; Druey, Kirk M

2018-02-16

Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource. ©2018 Society for Leukocyte Biology.

Asthma and subjective sleep disordered breathing in a large cohort of urban adolescents.

PubMed

Zandieh, Stephanie O; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M; Bruzzese, Jean-Marie

2017-01-02

Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. 12% reported SDB symptoms. Older and bi-racial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p <.001). Compared to those without probable asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p <.001). Among those with probable asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma.

Asthma and Subjective Sleep Disordered Breathing in a Large Cohort of Urban Adolescents

PubMed Central

Zandieh, Stephanie O.; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M.; Bruzzese, Jean-Marie

2017-01-01

Objective Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. Methods 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. Results 12% reported SDB symptoms. Older and biracial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p<.001). Compared to those without probable asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p<.001). Among those with probable asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. Conclusions In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma. PMID:27740900

Predictors of quality of life: A quantitative investigation of the stress-coping model in children with asthma

PubMed Central

Peeters, Yvette; Boersma, Sandra N; Koopman, Hendrik M

2008-01-01

Background Aim of this study is to further explore predictors of health related quality of life in children with asthma using factors derived from to the extended stress-coping model. While the stress-coping model has often been used as a frame of reference in studying health related quality of life in chronic illness, few have actually tested the model in children with asthma. Method In this survey study data were obtained by means of self-report questionnaires from seventy-eight children with asthma and their parents. Based on data derived from these questionnaires the constructs of the extended stress-coping model were assessed, using regression analysis and path analysis. Results The results of both regression analysis and path analysis reveal tentative support for the proposed relationships between predictors and health related quality of life in the stress-coping model. Moreover, as indicated in the stress-coping model, HRQoL is only directly predicted by coping. Both coping strategies 'emotional reaction' (significantly) and 'avoidance' are directly related to HRQoL. Conclusion In children with asthma, the extended stress-coping model appears to be a useful theoretical framework for understanding the impact of the illness on their quality of life. Consequently, the factors suggested by this model should be taken into account when designing optimal psychosocial-care interventions. PMID:18366753

Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: A meta-analysis.

PubMed

Zhao, Dong-Dong; Yu, Dan-Dan; Ren, Qiong-Qiong; Dong, Bao; Zhao, Feng; Sun, Ye-Huan

2017-04-01

As for the association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to pediatric asthma, results of published studies yielded conflicts. A systematic review was conducted on the relationship between childhood asthma and VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236). PubMed, Web of Science, CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) database were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated. Overall results suggested that there was a statistically significant association between ApaI polymorphism and childhood asthma in homozygote model (OR = 1.674, 95%CI = 1.269-2.208, P < 0.001) and allele model (OR = 1.221, 95%CI = 1.084-1.375, P = 0.001). Stratification by ethnicity revealed a statistical association in Asians (OR = 1.389, 95%CI = 1.178-1.638, P < 0.001). There was some evidence of an association between BsmI polymorphism and childhood asthma in the homozygote (OR = 1.462, 95%CI = 1.016-2.105, P = 0.041) and allele models (OR = 1.181, 95%CI = 1.006-1.386, P = 0.042). This association reached significance only in the Caucasian group (OR = 1.236, 95%CI = 1.029-1.485, P = 0.023). For FokI, a statistical association was detected in dominant model (OR = 1.281, 95%CI = 1.055-1.555, P = 0.012); this association was significant in allele model (OR = 1.591, 95%CI = 1.052-2.405, P = 0.028) in Caucasian. ApaI polymorphism plays a particular role in childhood asthma in Asians. FokI polymorphism may be connected with pediatric asthma in Caucasian population. And BsmI polymorphism marginally contributes to childhood asthma susceptibility, while there might be no association between TaqI polymorphism and childhood asthma risk. Pediatr Pulmonol. 2017;52:423-429. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prophylactic Bifidobacterium adolescentis ATTCC 15703 supplementation reduces partially allergic airway disease in Balb/c but not in C57BL/6 mice.

PubMed

Casaro, M C; Crisma, A R; Vieira, A T; Silva, G H M; Mendes, E; Ribeiro, W R; Martins, F S; Ferreira, C M

2018-04-25

Allergic asthma is a chronic disease mainly characterised by eosinophil inflammation and airway remodelling. Many studies have shown that the gut microbiota of allergic individuals differs from that of non-allergic individuals. Although high levels of bifidobacteria have been associated with healthy persons, Bifidobacterium adolescentis ATCC 15703, a gut bacteria, has been associated with allergic individuals in some clinical studies. The relationship between B. adolescentis ATCC 15703 and asthma or allergies has not been well elucidated, and its effect may be dependent on the host's genetic profile or disease state. To elucidate this question, we evaluated the role of preventive B. adolescentis ATCC 15703 treatment on experimental allergic airway inflammation in two genetically different mouse strains, Balb/c and C57BL/6 (B6). Balb/c mice display a greater predisposition to develop allergic responses than B6 mice. Oral preventive treatment with B. adolescentis ATCC 15703 modulated experimental allergic airway inflammation, specifically in Balb/c mice, which showed decreased levels of eosinophils in the airway. B6 mice did not exhibit any significant alterations in eosinophils but showed an increased influx of total leukocytes and neutrophils into the airway. The mechanism underlying the beneficial effects of these bacteria in experimental allergic mice may involve products of bacteria metabolism, as dead bacteria did not mimic the ability of live B. adolescentis ATCC 15703 to attenuate the influx of eosinophils into the airway. To conclude, preventive oral B. adolescentis ATCC 15703 treatment can attenuate the major characteristic of allergic asthma, eosinophil airway influx, in Balb/c but not B6 mice. These results suggest that oral treatment with this specific live bacterial strain may have therapeutic potential for the treatment of allergic airway disease, although its effect is mouse-strain-dependent.

Eotaxin-rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response

PubMed Central

Asosingh, Kewal; Vasanji, Amit; Tipton, Aaron; Queisser, Kimberly; Wanner, Nicholas; Janocha, Allison; Grandon, Deepa; Anand-Apte, Bela; Rothenberg, Marc. E.; Dweik, Raed; Erzurum, Serpil C.

2016-01-01

Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge, and prior to airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and murine model of asthma. Exvivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wildtype mice transplanted with eotaxin-1/2 deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, while adoptive transfer of proangiogenic progenitor cells from wildtype mice in an atopic asthma model into the eotaxin-1/2 deficient mice led to angiogenesis and airway inflammation. The findings indicate that TH2-promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation. PMID:26810221

Estimating Wisconsin Asthma Prevalence Using Clinical Electronic Health Records and Public Health Data

PubMed Central

Tomasallo, Carrie D.; Hanrahan, Lawrence P.; Tandias, Aman; Chang, Timothy S.; Cowan, Kelly J.

2014-01-01

Objectives. We compared a statewide telephone health survey with electronic health record (EHR) data from a large Wisconsin health system to estimate asthma prevalence in Wisconsin. Methods. We developed frequency tables and logistic regression models using Wisconsin Behavioral Risk Factor Surveillance System and University of Wisconsin primary care clinic data. We compared adjusted odds ratios (AORs) from each model. Results. Between 2007 and 2009, the EHR database contained 376 000 patients (30 000 with asthma), and 23 000 (1850 with asthma) responded to the Behavioral Risk Factor Surveillance System telephone survey. AORs for asthma were similar in magnitude and direction for the majority of covariates, including gender, age, and race/ethnicity, between survey and EHR models. The EHR data had greater statistical power to detect associations than did survey data, especially in pediatric and ethnic populations, because of larger sample sizes. Conclusions. EHRs can be used to estimate asthma prevalence in Wisconsin adults and children. EHR data may improve public health chronic disease surveillance using high-quality data at the local level to better identify areas of disparity and risk factors and guide education and health care interventions. PMID:24228643

The integrated care of asthma in Switzerland (INCAS)-study: Patients' perspective of received asthma care and their interest in asthma education.

PubMed

Dürr, Selina; Hersberger, Kurt E; Zeller, Andreas; Scheuzger, Jonas; Miedinger, David; Gregoriano, Claudia; Leuppi, Jörg D; Steurer-Stey, Claudia

2016-11-01

For successful long-term asthma care, self-management education is a cornerstone. Little is known about associations between patients' interest in education, asthma control and care delivery. We compared patients' characteristics, asthma control and patients' perspective about asthma care in subjects with and without interest in asthma education. Moreover, we assessed reasons, why patients denied participating in asthma education. Baseline data of 223 patients with asthma (age 43 ± 12 years, 38% male, 58% non-smokers, 13% current smokers), who participated in a multicentre longitudinal controlled study, are reported. At baseline, patients completed the Asthma Control Test (ACT), the Patient Assessment Chronic Illness Care questionnaire (PACIC 5A) and stated their interest in an asthma education programme. Overall, 34% of all participants showed uncontrolled asthma. One hundred and twenty-five (56%) patients were interested in education. Compared to patients without interest, they were characterised by male gender (p = 0.013), worse asthma control (p < 0.001), and perception of lower quality of chronic asthma care delivery, in particular lower self-management support (p < 0.001). Main reasons for rejecting asthma education were having sufficient asthma knowledge, having only mild asthma, receiving adequate medical support and lack of time. More than half of the patients were interested in asthma education. Interest was associated with worse asthma control and lower receipt of care according to the Chronic Care Model. Considering these aspects, this approach may help to improve care quality and allow targeting interventions to those patients who are interested in becoming active participants in their care and who might benefit most.

Factors related to poor asthma control in Latvian asthma patients between 2013 and 2015

PubMed Central

Smits, Dins; Brigis, Girts; Pavare, Jana; Maurina, Baiba; Barengo, Noël Christopher

2017-01-01

Objectives To investigate whether beliefs about asthma medication, cognitive and emotional factors are related to poor asthma control in a sample of Latvian asthma patients in 2015. Design Cross-sectional, self-administered survey. Subjects Three hundred and fifty two asthma patients (mean age 57.5 years) attending outpatient pulmonologist consultations in Riga, Latvia during September 2013 to December 2015. The sample size was calculated to detect a prevalence of poor asthma control of 50% with a margin of error of 5% and a power of 95%. Main outcome measures The validated Beliefs about Medication Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Good asthma control was assessed using the asthma control test (ACT), a validated five-item scale that reliably assesses asthma control over a recall period of four weeks. Logistic regression models were used to predict poor asthma control. Results Patients who had a good control of asthma medication (OR 0.70; 95% CI 0.61–0.79) or were confident that their asthma medication improves illness (OR 0.84; 95% CI 0.74–0.95) had a reduced risk of poor asthma control. The more symptoms (OR 1.63; 95% CI 1.44–1.84) the asthma patients perceived or the more their illness affects their life, the higher the probability of poor asthma control (OR 1.47; 95% CI 1.31–1.65). Some beliefs of necessity and concerns of asthma medication were also statistically significantly related to poor asthma control. Conclusions Beliefs of necessity of asthma medication, cognitive and emotional illness perception factors correlate well with poor asthma control in Latvian patients. PMID:28585881

Improving predictive asthma algorithms with modelled environment data for Scotland: an observational cohort study protocol.

PubMed

Soyiri, Ireneous N; Sheikh, Aziz; Reis, Stefan; Kavanagh, Kimberly; Vieno, Massimo; Clemens, Tom; Carnell, Edward J; Pan, Jiafeng; King, Abby; Beck, Rachel C; Ward, Hester J T; Dibben, Chris; Robertson, Chris; Simpson, Colin R

2018-05-20

Asthma has a considerable, but potentially, avoidable burden on many populations globally. Scotland has some of the poorest health outcomes from asthma. Although ambient pollution, weather changes and sociodemographic factors have been associated with asthma attacks, it remains unclear whether modelled environment data and geospatial information can improve population-based asthma predictive algorithms. We aim to create the afferent loop of a national learning health system for asthma in Scotland. We will investigate the associations between ambient pollution, meteorological, geospatial and sociodemographic factors and asthma attacks. We will develop and implement a secured data governance and linkage framework to incorporate primary care health data, modelled environment data, geospatial population and sociodemographic data. Data from 75 recruited primary care practices (n=500 000 patients) in Scotland will be used. Modelled environment data on key air pollutants at a horizontal resolution of 5 km×5 km at hourly time steps will be generated using the EMEP4UK atmospheric chemistry transport modelling system for the datazones of the primary care practices' populations. Scottish population census and education databases will be incorporated into the linkage framework for analysis. We will then undertake a longitudinal retrospective observational analysis. Asthma outcomes include asthma hospitalisations and oral steroid prescriptions. Using a nested case-control study design, associations between all covariates will be measured using conditional logistic regression to account for the matched design and to identify suitable predictors and potential candidate algorithms for an asthma learning health system in Scotland.Findings from this study will contribute to the development of predictive algorithms for asthma outcomes and be used to form the basis for our learning health system prototype. The study received National Health Service Research Ethics Committee approval (16/SS/0130) and also obtained permissions via the Public Benefit and Privacy Panel for Health and Social Care in Scotland to access, collate and use the following data sets: population and housing census for Scotland; Scottish education data via the Scottish Exchange of Data and primary care data from general practice Data Custodians. Analytic code will be made available in the open source GitHub website. The results of this study will be published in international peer reviewed journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect modification of perinatal exposure to air pollution and childhood asthma incidence

PubMed Central

Lavigne, Éric; Bélair, Marc-André; Rodriguez Duque, Daniel; Do, Minh T.; Stieb, David M.; Hystad, Perry; van Donkelaar, Aaron; Martin, Randall V.; Crouse, Daniel L.; Crighton, Eric; Chen, Hong; Burnett, Richard T.; Weichenthal, Scott; Villeneuve, Paul J.; To, Teresa; Brook, Jeffrey R.; Johnson, Markey; Cakmak, Sabit; Yasseen, Abdool S.; Walker, Mark

2018-01-01

Perinatal exposure to ambient air pollution has been associated with childhood asthma incidence; however, less is known regarding the potential effect modifiers in this association. We examined whether maternal and infant characteristics modified the association between perinatal exposure to air pollution and development of childhood asthma. 761 172 births occurring between 2006 and 2012 were identified in the province of Ontario, Canada. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6 years) were estimated using Cox regression models. 110 981 children with asthma were identified. In models adjusted for postnatal exposures, second-trimester exposures to particulate matter with a 50% cut-off aerodynamic diameter ≤2.5 μm (hazard ratio (HR) per interquartile range (IQR) increase 1.07, 95% CI 1.06–1.09) and nitrogen dioxide (HR per IQR increase 1.06, 95% CI 1.03–1.08) were associated with childhood asthma development. Enhanced impacts were found among children born to mothers with asthma, who smoked during pregnancy or lived in urban areas during pregnancy, males and children born preterm or of low birthweight. Prenatal exposure to air pollution may have a differential impact on the risk of asthma development, according to maternal and infant characteristics. PMID:29419440

Short-term effects of airborne pollens on asthma attacks as seen by general practitioners in the Greater Paris area, 2003-2007.

PubMed

Huynh, Bich Tram; Tual, Séverine; Turbelin, Clément; Pelat, Camille; Cecchi, Lorenzo; D'Amato, Gennaro; Blanchon, Thierry; Annesi-Maesano, Isabella

2010-09-01

To investigate for the first time the short-term effects of airborne pollen counts on general practitioner (GP) consultations for asthma attacks in the Greater Paris area between 2003-2007. Counts were available for common pollens (Betula, Cupressa, Fraxinus and Poaceae). Weekly data on GP visits for asthma attacks were obtained from the French GP Sentinel Network. A quasi-Poisson regression with generalised additive models was implemented. Short-term effects of pollen counts were assessed using single and multi-pollen models after adjustment for air pollution and influenza. A mean weekly incidence rate of 25.4 cases of asthma attacks per 100,000 inhabitants was estimated during the study period. The strongest significant association between asthma attacks and pollen counts was registered for grass (Poaceae) in the same week of asthma attacks, with a slight reduction of the effect observed in the multi-pollen model. Adjusted relative risk for Poaceae was 1.54 (95% CI: 1.33-1.79) with an inter-quartile range increase of 17.6 grains/m3 during the pollen season. For the first time, a significant short-term association was observed between Poaceae pollen counts and consultations for asthma attacks as seen by GPs. These findings need to be confirmed by more consistent time-series and investigations on a daily basis.

A Jagged 1-Notch 4 molecular switch mediates airway inflammation induced by ultrafine particles.

PubMed

Xia, Mingcan; Harb, Hani; Saffari, Arian; Sioutas, Constantinos; Chatila, Talal A

2018-04-05

Exposure to traffic-related particulate matter promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which particulate matter exposure acts to mediate these effects remain unclear. We sought to elucidate the cellular targets and signaling pathways critical for augmentation of allergic airway inflammation induced by ambient ultrafine particles (UFP). We used in vitro cell-culture assays with lung-derived antigen-presenting cells and allergen-specific T cells and in vivo mouse models of allergic airway inflammation with myeloid lineage-specific gene deletions, cellular reconstitution approaches, and antibody inhibition studies. We identified lung alveolar macrophages (AM) as the key cellular target of UFP in promoting airway inflammation. Aryl hydrocarbon receptor-dependent induction of Jagged 1 (Jag1) expression in AM was necessary and sufficient for augmentation of allergic airway inflammation by UFP. UFP promoted T H 2 and T H 17 cell differentiation of allergen-specific T cells in a Jag1- and Notch 4-dependent manner. Treatment of mice with an anti-Notch 4 antibody abrogated exacerbation of allergic airway inflammation induced by UFP. UFP exacerbate allergic airway inflammation by promoting a Jag1-Notch 4-dependent interaction between AM and allergen-specific T cells, leading to augmented T H cell differentiation. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Poor asthma control and exposure to traffic pollutants and obesity in older adults

PubMed Central

Epstein, Tolly G.; Ryan, Patrick H.; LeMasters, Grace K.; Bernstein, Cheryl K.; Levin, Linda S.; Bernstein, Jonathan A.; Villareal, Manuel S.; Bernstein, David I.

2015-01-01

Background Environmental and host predictors of asthma control in older asthmatic patients (>65 years old) are poorly understood. Objective To examine the effects of residential exposure to traffic exhaust and other environmental and host predictors on asthma control in older adults. Methods One hundred four asthmatic patients 65 years of age or older from allergy and pulmonary clinics in greater Cincinnati, Ohio, completed the validated Asthma Control Questionnaire (ACQ), pulmonary function testing, and skin prick testing to 10 common aeroallergens. Patients had a physician’s diagnosis of asthma, had significant reversibility in forced expiratory volume in 1 second or a positive methacholine challenge test result, and did not have chronic obstructive pulmonary disease. The mean daily residential exposure to elemental carbon attributable to traffic (ECAT) was estimated using a land-use regression model. Regression models were used to evaluate associations among independent variables, ACQ scores, and the number of asthma exacerbations, defined as acute worsening of asthma symptoms requiring prednisone use, in the past year. Results In the adjusted model, mean daily residential exposure to ECAT greater than 0.39 µg/m3 was significantly associated with poorer asthma control based on ACQ scores (adjusted β = 2.85; 95% confidence interval [CI], 0.58–5.12; P = .02). High ECAT levels were also significantly associated with increased risk of asthma exacerbations (adjusted odds ratio, 3.24; 95% CI, 1.01–10.37; P = .05). A significant association was found between higher body mass index and worse ACQ scores (adjusted β = 1.15; 95% CI, 0.53–1.76; P < .001). Atopic patients (skin prick test positive) had significantly better ACQ scores than nonatopic patients (adjusted β = −0.39; 95% CI, −0.67 to −0.11; P < .01). Conclusion Higher mean daily residential exposure to traffic exhaust, obesity, and nonatopic status are associated with poorer asthma control among older asthmatic patients. PMID:22626595

Testing evidence routine practice: Using an implementation framework to embed a clinically proven asthma service in Australian community pharmacy.

PubMed

Fuller, Joanne M; Saini, Bandana; Bosnic-Anticevich, Sinthia; Garcia Cardenas, Victoria; Benrimoj, Shalom I; Armour, Carol

Community pharmacists are well placed and evidence clearly demonstrates that they can be suitably trained to deliver professional services that improve the management of asthma patients in clinical, economic and humanistic terms. However the gap between this evidence and practice reality remains wide. In this study we measure the implementation process as well as the service benefits of an asthma service model. Using an effectiveness-implementation hybrid design, a defined implementation process (progression from Exploration through Preparation and Testing to Operation stages) supporting an asthma service (promoting asthma control and inhaler technique) was tested in 17 community pharmacies across metropolitan Sydney. Seven pharmacies reached the Operation stage of implementation. Eight pharmacies reached the Testing stage of implementation and two pharmacies did not progress beyond the Preparation stage of implementation. A total of 128 patients were enrolled in the asthma service with 110 patients remaining enrolled at the close of the study. Asthma control showed a positive trend throughout the service with the overall proportion of patients with 'poor' asthma control at baseline decreasing from 72% to 57% at study close. There was a statistically significant increase in the proportion of patients with correct inhaler technique from 12% at Baseline (Visit 1) to 33% at Visit 2 and 57% at study close. Implementation of the asthma service varied across pharmacies. Different strategies specific to practice sites at different stages of the implementation model may result in greater uptake of professional services. The asthma service led to improved patient outcomes overall with a positive trend in asthma control and significant change in inhaler technique. Copyright © 2017 Elsevier Inc. All rights reserved.

Patient preferences for community pharmacy asthma services: a discrete choice experiment.

PubMed

Naik-Panvelkar, Pradnya; Armour, Carol; Rose, John M; Saini, Bandana

2012-10-01

Specialized community pharmacy services, involving the provision of disease state management and care by pharmacists, have been developed and trialled and have demonstrated very good health outcomes. Most of these services have been developed from a healthcare professional perspective. However, for the future uptake and long-term sustainability of these services as well as for better and sustained health outcomes for patients, it is vital to gain an understanding of patients' preferences. We can then structure healthcare services to match these preferences and needs rather than around clinical viewpoints alone. The aim of this study was to elicit patient preferences for pharmacy-based specialized asthma services using a discrete choice experiment and to explore the value/importance that patients place on the different attributes of the asthma service. The existence of preference heterogeneity in the population was also investigated. The study was conducted with asthma patients who had recently experienced a specialized asthma management service at their pharmacy in New South Wales, Australia. Pharmacists delivering the asthma service mailed out the discrete choice questionnaires to participating patients at the end of 6 months of service provision. A latent class (LC) model was used to investigate each patient's strength of preference and preference heterogeneity for several key attributes related to asthma service provision: frequency of visits, access to pharmacist, interaction with pharmacy staff, availability of a private area for consultation, provision of lung function testing, type and depth of advice provision, number of days with asthma symptoms and cost of service. Eighty useable questionnaires (of 170 questionnaires sent out) were received (response rate 47.1%). The study identified various key elements of asthma services important to patients. Further, the LC analysis revealed three classes with differing patient preferences for levels of asthma service provision. Patients in the Minimalistic Model class valued provision of lung function testing and preferred more frequent service visits. Cost of service had a negative effect on service preference for patients in this class. Patients in the Partial Model class mainly derived utility from the provision of lung function testing and comprehensive advice at the pharmacy and also wanted more frequent service visits. The Holistic Model class patients considered all attributes of the service to be important when making a choice. While the majority of the service attributes had a positive effect on preference for patients in this class, cost of service and days with symptoms of asthma had a negative effect on service preference. These patients also preferred fewer service visits. The study identified various key attributes that are important to patients with respect to community pharmacy-based asthma services. The results also demonstrate the existence of preference heterogeneity in the population. Asthma service providers need to take these findings into consideration in the design and development of future service models so as to increase their uptake and ensure their long-term sustainability.

Obesity increases the prevalence and the incidence of asthma and worsens asthma severity.

PubMed

Barros, R; Moreira, P; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Moreira, A

2017-08-01

We aimed to explore the association between obesity and asthma prevalence, incidence and severity. The study included 32,644 adults, 52.6% female, from a representative sample of the 4th Portuguese National Health Survey. The following asthma definitions were used: ever asthma (ever medical doctor asthma diagnosis), current asthma (asthma within the last 12 months), current persistent asthma (required asthma medication within the last 12 months), current severe asthma (attending an emergency department because of asthma within the last 12 months), and incident asthma (asthma diagnosis within the last 12 months). Body mass index was calculated based on self-reported weight and height and categorised according to WHO classification. Logistic regression models adjusted for confounders were performed. Prevalence of ever asthma was 5.3%, current asthma 3.5%, current persistent asthma 3.0%, current severe asthma 1.4%, and incident asthma 0.2%. Prevalence of obesity was 16%, overweight 37.6%, normal weight 44.6% and underweight 0.2%. Being overweight, obesity class I and II, and obesity class III were associated with an OR (95% CI) with ever asthma 1.22 (1.21-1.24), 1.39 (1.36-1.41), 3.24 (3.08-3.40) respectively; current asthma 1.16 (1.14-1.18), 1.86 (1.82-1.90), 4.73 (4.49-4.98) respectively; current persistent asthma 1.08 (1.06-1.10), 2.06 (2.01-2.10), 5.24 (4.96-5.53), and current severe asthma 1.36 (1.32-1.40), 1.50 (1.45-1.55) and 3.70 (3.46-3.95), respectively. Considering the incidence of asthma, obesity more than quadrupled the odds (OR = 4.46, 95% CI 4.30, 4.62). Obesity is associated in a dose dependent way with an increase of prevalent and incident asthma, and it seems to increase the odds of a more persistent and severe asthma phenotype independently of socio-demographic determinants, physical activity, and dietary patterns. Our results provide rational for future lifestyle intervention studies for weight reduction in the obesity-asthma phenotype. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Obese and Allergic Related Asthma Phenotypes Among Children Across the United States.

PubMed

Ross, Mindy K; Romero, Tahmineh; Sim, Myung S; Szilagyi, Peter G

2018-04-19

Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity and allergy related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and parent-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with parent-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. Among 4,427 children with asthma in this NSCH cohort, the association between race and phenotype is statistically significant (p<0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-non-allergic phenotype (p<0.001). ADD/ADHD was more likely to be present in allergic-not-obese children (OR 1.50, CI 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p<0.001). Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the U.S. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

How does patient-provider communication influence adherence to asthma medications?

PubMed

Young, Henry N; Len-Rios, Maria E; Brown, Roger; Moreno, Megan M; Cox, Elizabeth

2017-04-01

To assess hypothesized pathways through which patient-provider communication impacts asthma medication adherence. A national sample of 452 adults with asthma reported assessments of patient-provider communication, proximal outcomes (understanding of asthma self-management, patient-provider agreement, trust in the clinician, involvement in care, motivation), and adherence to asthma medications. Structural equation modeling was used to examine hypothesized pathways. Significantly positive direct pathways were found between patient-provider communication and all proximal outcomes. Only positive indirect pathways, operating through trust and motivation, were found between patient-provider communication and medication adherence. Patient-provider communication influences many desirable proximal outcomes, but only influences adherence through trust and motivation. To promote better adherence to asthma medication regimens and, ultimately positive asthma outcomes, healthcare providers can focus on implementing communication strategies that strengthen patients' trust and increase patient motivation to use asthma medications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The neonatal methylome as a gatekeeper in the trajectory to childhood asthma.

PubMed

DeVries, Avery; Vercelli, Donata

2017-04-01

Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome. All of these studies specifically surveyed human DNA methylation and involved a genome-wide component. In combination, their results broaden our understanding of asthma pathogenesis and the role the methylome plays in this process.

Comparative Effectiveness on Cognitive Asthma Outcomes of the SHARP Academic Asthma Health Education and Counseling Program and a Non-Academic Program

PubMed Central

Kintner, Eileen; Cook, Gwendolyn; Marti, C. Nathan; Stoddard, Debbie; Gomes, Melissa; Harmon, Phyllis; Van Egeren, Laurie A.

2018-01-01

Asthma morbidity and mortality is higher among older school-age children and early adolescents than other age groups across the lifespan. NIH recommended expanding asthma education to schools and community settings to meet cognitive outcomes that have an impact on morbidity and mortality. Guided by the acceptance of asthma model, an evidence-guided, comprehensive school-based academic health education and counseling program, Staying Healthy—Asthma Responsible & Prepared™ (SHARP), was developed. The program complements existing school curricula by integrating biology, psychology, and sociology content with related spelling, math, and reading and writing assignments. Feasibility, benefits, and efficacy have been established. We compared the effectiveness of SHARP to a non-academic program, Open Airways for Schools, in improving asthma knowledge and reasoning about symptom management. A two-group, cluster-randomized, single-blinded design was used with a sample of 205 students in grades 4–5 with asthma and their caregivers. Schools were matched prior to randomization. The unit of analysis was the student. Certified elementary school teachers delivered the programs during instructional time. Data were collected from student/caregiver dyads at baseline and at 1, 12, and 24 months after the intervention. In multilevel modeling, students enrolled in the academic SHARP program demonstrated significant (p<.001) improvement in asthma knowledge and reasoning over students enrolled in the non-academic program. Knowledge advantages were retained at 24 months. Findings support delivery in schools of the SHARP academic health education program for students with asthma. PMID:26296595

Th2 cytokine antagonists: potential treatments for severe asthma.

PubMed

Hansbro, Philip M; Scott, Grace V; Essilfie, Ama-Tawiah; Kim, Richard Y; Starkey, Malcolm R; Nguyen, Duc H; Allen, Paul D; Kaiko, Gerard E; Yang, Ming; Horvat, Jay C; Foster, Paul S

2013-01-01

Asthma is a major disease burden worldwide. Treatment with steroids and long acting β-agonists effectively manage symptoms in many patients but do not treat the underlying cause of disease and have serious side effects when used long term and in children. Therapies targeting the underlying causes of asthma are urgently needed. T helper type 2 (Th2) cells and the cytokines they release are clinically linked to the presentation of all forms of asthma. They are the primary drivers of mild to moderate and allergic asthma. They also play a pathogenetic role in exacerbations and more severe asthma though other factors are also involved. Much effort using animal models and human studies has been dedicated to the identification of the pathogenetic roles of these cells and cytokines and whether inhibition of their activity has therapeutic benefit in asthma. We discuss the current status of Th2 cytokine antagonists for the treatment of asthma. We also discuss the potential for targeting Th2-inducing cytokines, Th2 cell receptors and signaling as well as the use of Th2 cell antagonists, small interfering oligonucleotides, microRNAs, and combination therapies. Th2 antagonists may be most effective in particular asthma subtypes/endotypes where specific cytokines are known to be active through the analysis of biomarkers. Targeting common receptors and pathways used by these cytokines may have additional benefit. Animal models have been valuable in identifying therapeutic targets in asthma, however the results from such studies need to be carefully interpreted and applied to appropriately stratified patient cohorts in well-designed clinical studies and trials.

Comparative Effectiveness on Cognitive Asthma Outcomes of the SHARP Academic Asthma Health Education and Counseling Program and a Non-Academic Program.

PubMed

Kintner, Eileen; Cook, Gwendolyn; Marti, C Nathan; Stoddard, Debbie; Gomes, Melissa; Harmon, Phyllis; Van Egeren, Laurie A

2015-12-01

Asthma morbidity and mortality is higher among older school-age children and early adolescents than other age groups across the lifespan. NIH recommended expanding asthma education to schools and community settings to meet cognitive outcomes that have an impact on morbidity and mortality. Guided by the acceptance of asthma model, an evidence-guided, comprehensive school-based academic health education and counseling program, Staying Healthy-Asthma Responsible & Prepared™ (SHARP), was developed. The program complements existing school curricula by integrating biology, psychology, and sociology content with related spelling, math, and reading and writing assignments. Feasibility, benefits, and efficacy have been established. We compared the effectiveness of SHARP to a non-academic program, Open Airways for Schools, in improving asthma knowledge and reasoning about symptom management. A two-group, cluster-randomized, single-blinded design was used with a sample of 205 students in grades 4-5 with asthma and their caregivers. Schools were matched prior to randomization. The unit of analysis was the student. Certified elementary school teachers delivered the programs during instructional time. Data were collected from student/caregiver dyads at baseline and at 1, 12, and 24 months after the intervention. In multilevel modeling, students enrolled in the academic SHARP program demonstrated significant (p< .001) improvement in asthma knowledge and reasoning over students enrolled in the non-academic program. Knowledge advantages were retained at 24 months. Findings support delivery in schools of the SHARP academic health education program for students with asthma. © 2015 Wiley Periodicals, Inc.

Air pollution is associated with primary health care visits for asthma in Sweden: A case-crossover design with a distributed lag non-linear model.

PubMed

Taj, Tahir; Jakobsson, Kristina; Stroh, Emilie; Oudin, Anna

2016-05-01

Air pollution can increase the symptoms of asthma and has an acute effect on the number of emergency room visits and hospital admissions because of asthma, but little is known about the effect of air pollution on the number of primary health care (PHC) visits for asthma. To investigate the association between air pollution and the number of PHC visits for asthma in Scania, southern Sweden. Data on daily PHC visits for asthma were obtained from a regional healthcare database in Scania, which covers approximately half a million people. Air pollution data from 2005 to 2010 were obtained from six urban background stations. We used a case-crossover study design and a distributed lag non-linear model in the analysis. The air pollution levels were generally within the EU air quality guidelines. The mean number of daily PHC visits for asthma was 34. The number of PHC visits increased by 5% (95% confidence interval (CI): 3.91-6.25%) with every 10µg m(-3) increase in daily mean NO2 lag (0-15), suggesting that daily air pollution levels are associated with PHC visits for asthma. Even though the air quality in Scania between 2005 and 2010 was within EU's guidelines, the number of PHC visits for asthma increased with increasing levels of air pollution. This suggests that as well as increasing hospital and emergency room visits, air pollution increases the burden on PHC due to milder symptoms of asthma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Presentations to Alberta emergency departments for asthma: a time series analysis.

PubMed

Rosychuk, Rhonda J; Youngson, Erik; Rowe, Brian H

2015-08-01

Asthma is a common chronic respiratory condition, and exacerbations may cause individuals to seek care in emergency departments (EDs). This study examines the monthly patterns of asthma presentations to EDs in Alberta, Canada. All presentations to the ED for asthma from April 1999 to March 2011 were extracted from provincial administrative health databases. Data included age, sex, and health zone of residence. Crude rates per 100,000 population were calculated. Seasonal autoregressive integrated moving average (SARIMA) time-series models were developed. There were a total of 362,430 ED presentations for asthma, and the monthly rate of presentation declined from 115.5 to 41.6 per 100,000 during the study period. Males made 50.1% of ED presentations, and adults made 52.8%. The absolute number of ED presentations for asthma declined in each of the five administrative health zones in the province, with smaller percentage decreases seen in the most urbanized zones (32.1%) than the other zones (46.9%). One SARIMA model closely predicted overall presentation rates as well as the rates of ED presentations for age and zone subgroups. These models showed strong seasonal components, with the strongest estimates occurring for the pediatric subgroup and the southernmost provincial zone. Rates of ED presentations for asthma have been declining in this province during the past decade. The reasons for this decline warrant further exploration. The SARIMA models quantified the temporal patterns and may be helpful for planning research and health care service needs. © 2015 by the Society for Academic Emergency Medicine.

Recent developments in the role of reactive oxygen species in allergic asthma

PubMed Central

Qu, Jingjing; Li, Yuanyuan; Zhong, Wen

2017-01-01

Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma. Among these mediators, endogenous or exogenous ROS are responsible for the airway inflammation of allergic asthma. Furthermore, several inflammatory cells induce ROS and allergic asthma development. Airway inflammation, airway hyper-responsiveness, tissue injury, and remodeling can be induced by excessive ROS production in animal models. Based on investigations of allergic asthma and ROS formation mechanisms, we have identified several novel anti-inflammatory therapeutic treatments. This review describes the recent data linking ROS to the pathogenesis of allergic asthma. PMID:28203435

Psychological characteristics of patients with asthma.

PubMed

Bulcun, Emel; Turkel, Yakup; Oguztürk, Omer; Dag, Ersel; Visal Buturak, S; Ekici, Aydanur; Ekici, Mehmet

2018-01-01

Psychological distress of patients with asthma may be reduced when they learned to live with their illness. Asthma can change the psychological and personality characteristics. We aim to investigate the psychological and personality characteristics of patients with asthma using MMPI (Minnesota Multiphasic Personality Inventory). Thirty-three adult patients with asthma (23 female and 10 male) and 20 healthy controls (14 females and 6 males) were enrolled in this study. Psychometric evaluation was made with the Turkish version of the MMPI. The patients were separated into two groups according to the duration of symptoms (recent-onset asthma < 10 years, long-standing asthma ≥10 years). Patients with asthma compared with control group had significantly higher the rate of clinical elevation on depression, hysteria, psychasthenia and social introversion. Patients with recent-onset asthma compared with long-standing asthma have significantly higher the rate of clinical elevation on depression, hysteria, psychopathic deviate, psychasthenia and social introversion. MMPI mean t score in patients with recent-onset asthma was higher than patients with long-standing asthma. MMPI mean t score in patients with asthma was negatively associated with the symptom duration in multivariate model. Patients with asthma have relatively more inactivity, anergia, guilt, pessimism, nonspecific physical complaints, irrational fears and introvert. Patients with long-standing asthma have less psychological distress, suggesting that learned to cope with his illness. © 2016 John Wiley & Sons Ltd.

Cost-effectiveness and Budget Impact of Routine Use of Fractional Exhaled Nitric Oxide Monitoring for the Management of Adult Asthma Patients in Spain.

PubMed

Sabatelli, L; Seppälä, U; Sastre, J; Crater, G

Fractional exhaled nitric oxide (FeNO) is a marker for type 2 airway inflammation. The objective of this study was to evaluate the cost-effectiveness and budget impact of FeNO monitoring for management of adult asthma in Spain. A cost-effectiveness analysis model was used to evaluate the effect on costs of adding FeNO monitoring to asthma management. Over a 1-year period, the model estimated the incremental cost per quality-adjusted life year and incremental number of exacerbations avoided when FeNO monitoring was added to standard guideline-driven asthma care compared with standard care alone. Univariate and multivariate sensitivity analyses were applied to explore uncertainty in the model. A budget impact model was used to examine the impact of FeNO monitoring on primary care costs across the Spanish health system. The results showed that adding FeNO to standard asthma care saved €62.53 per patient-year in the adult population and improved quality-adjusted life years by 0.026 per patient-year. The budget impact analysis revealed a potential net yearly saving of €129 million if FeNO monitoring had been used in primary care settings in Spain. The present economic model shows that adding FeNO to the treatment algorithm can considerably reduce costs and improve quality of life when used to manage asthma in combination with current treatment guidelines.

Social determinants of childhood asthma symptoms: an ecological study in urban Latin America.

PubMed

Fattore, Gisel L; Santos, Carlos A T; Barreto, Mauricio L

2014-04-01

Asthma is an important public health problem in urban Latin America. This study aimed to analyze the role of socioeconomic and environmental factors as potential determinants of asthma symptoms prevalence in children from Latin American (LA) urban centers. We selected 31 LA urban centers with complete data, and an ecological analysis was performed. According to our theoretical framework, the explanatory variables were classified in three levels: distal, intermediate, and proximate. The association between variables in the three levels and prevalence of asthma symptoms was examined by bivariate and multivariate linear regression analysis weighed by sample size. In a second stage, we fitted several linear regression models introducing sequentially the variables according to the predefined hierarchy. In the final hierarchical model Gini Index, crowding, sanitation, variation in infant mortality rates and homicide rates, explained great part of the variance in asthma prevalence between centers (R(2) = 75.0 %). We found a strong association between socioeconomic and environmental variables and prevalence of asthma symptoms in LA urban children, and according to our hierarchical framework and the results found we suggest that social inequalities (measured by the Gini Index) is a central determinant to explain high prevalence of asthma in LA.

Folate and asthma.

PubMed

Blatter, Joshua; Han, Yueh-Ying; Forno, Erick; Brehm, John; Bodnar, Lisa; Celedón, Juan C

2013-07-01

Findings from experimental studies and animal models led to the hypothesis that folic acid supplementation during pregnancy confers an increased risk of asthma. This review provides a critical examination of current experimental and epidemiologic evidence of a causal association between folate status and asthma. In industrialized nations, the prevalence of asthma was rising before widespread fortification of foodstuffs with folic acid or folate supplementation before or during pregnancy, thus suggesting that changes in folate status are an unlikely explanation for "the asthma epidemic." Consistent with this ecologic observation, evidence from human studies does not support moderate or strong effects of folate status on asthma. Given known protective effects against neural tube and cardiac defects, there is no reason to alter current recommendations for folic acid supplementation during conception or pregnancy based on findings for folate and asthma. Although we believe that there are inadequate data to exclude a weak effect of maternal folate status on asthma or asthma symptoms, such effects could be examined within the context of very large (and ongoing) birth cohort studies. At this time, there is no justification for funding new studies of folate and asthma.

A Nonlinear differential equation model of Asthma effect of environmental pollution using LHAM

NASA Astrophysics Data System (ADS)

Joseph, G. Arul; Balamuralitharan, S.

2018-04-01

In this paper, we investigated a nonlinear differential equation mathematical model to study the spread of asthma in the environmental pollutants from industry and mainly from tobacco smoke from smokers in different type of population. Smoking is the main cause to spread Asthma in the environment. Numerical simulation is also discussed. Finally by using Liao’s Homotopy analysis Method (LHAM), we found that the approximate analytical solution of Asthmatic disease in the environmental.

Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model.

PubMed

Eggo, Rosalind M; Scott, James G; Galvani, Alison P; Meyers, Lauren Ancel

2016-02-23

Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses--the "common cold" viruses--are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41-49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17-21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the "back-to-school" asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics.

Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model

PubMed Central

Scott, James G.; Galvani, Alison P.; Meyers, Lauren Ancel

2016-01-01

Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses—the “common cold” viruses—are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41–49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17–21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the “back-to-school” asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics. PMID:26858436

The Asthma Dialogues: A Model of Interactive Education for Skills

ERIC Educational Resources Information Center

Morrow, Robert; Fletcher, Jason; Mulvihill, Michael; Park, Heidi

2007-01-01

Introduction: A gap exists between asthma guidelines and actual care delivered. We developed an educational intervention using simulated physician-patient encounters as part of a project to improve asthma management by community-based primary care providers. We hypothesized that this type of skills-based interactive training would improve…

Association between Serum 25-Hydroxy Vitamin D Levels and the Prevalence of Adult-Onset Asthma.

PubMed

Cherrie, Mark P C; Sarran, Christophe; Osborne, Nicholas J

2018-05-29

The major circulating metabolite of vitamin D (25(OH)D) has been implicated in the pathogenesis for atopic dermatitis, asthma and other allergic diseases due to downstream immunomodulatory effects. However, a consistent association between 25(OH)D and asthma during adulthood has yet to be found in observational studies. We aimed to test the association between 25(OH)D and asthma during adulthood and hypothesised that this association would be stronger in non-atopic participants. Using information collected on the participants of the 1958 birth cohort, we developed a novel measure of atopic status using total and specific IgE values and reported history of eczema and allergic rhinitis. We designed a nested case-control analysis, stratified by atopic status, and using logistic regression models investigated the association between 25(OH)D measured at age 46 years with the prevalence of asthma and wheezy bronchitis at age 50 years, excluding participants who reported ever having asthma or wheezy bronchitis before the age of 42. In the fully adjusted models, a 10 nmol/L increase in serum 25(OH)D prevalence had a significant association with asthma (aOR 0.94; 95% CI 0.88⁻1.00). There was some evidence of an atopic dependent trend in the association between 25(OH)D levels and asthma. Further analytical work on the operationalisation of atopy status would prove useful to uncover whether there is a role for 25(OH)D and other risk factors for asthma.

Parental psychosocial stress and asthma morbidity in Puerto Rican twins.

PubMed

Lange, Nancy E; Bunyavanich, Supinda; Silberg, Judy L; Canino, Glorisa; Rosner, Bernard A; Celedón, Juan C

2011-03-01

Little is known about paternal psychosocial factors and childhood asthma. We sought to examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children. Parents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 year and again about their child's asthma at age 3 years. Fathers were asked about symptoms of posttraumatic stress disorder (PTSD), depression, and antisocial behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood. After multivariable adjustment, paternal PTSD symptoms, depression, and antisocial behavior were each associated with increased asthma symptoms at age 1 year (eg, odds ratio, 1.08 for each 1-point increase in PTSD score; 95% CI, 1.03-1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (odds ratio for each 1-point increase in symptoms, 1.16; 95% CI, 1.00-1.36). In an analysis combining 1- and 3-year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma. Both paternal and maternal psychosocial factors can influence asthma morbidity in young Puerto Rican children. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Development and evaluation of an innovative model of inter-professional education focused on asthma medication use

PubMed Central

2014-01-01

Background Inter-professional learning has been promoted as the solution to many clinical management issues. One such issue is the correct use of asthma inhaler devices. Up to 80% of people with asthma use their inhaler device incorrectly. The implications of this are poor asthma control and quality of life. Correct inhaler technique can be taught, however these educational instructions need to be repeated if correct technique is to be maintained. It is important to maximise the opportunities to deliver this education in primary care. In light of this, it is important to explore how health care providers, in particular pharmacists and general medical practitioners, can work together in delivering inhaler technique education to patients, over time. Therefore, there is a need to develop and evaluate effective inter-professional education, which will address the need to educate patients in the correct use of their inhalers as well as equip health care professionals with skills to engage in collaborative relationships with each other. Methods This mixed methods study involves the development and evaluation of three modules of continuing education, Model 1, Model 2 and Model 3. A fourth group, Model 4, acting as a control. Model 1 consists of face-to-face continuing professional education on asthma inhaler technique, aimed at pharmacists, general medical practitioners and their practice nurses. Model 2 is an electronic online continuing education module based on Model 1 principles. Model 3 is also based on asthma inhaler technique education but employs a learning intervention targeting health care professional relationships and is based on sociocultural theory. This study took the form of a parallel group, repeated measure design. Following the completion of continuing professional education, health care professionals recruited people with asthma and followed them up for 6 months. During this period, inhaler device technique training was delivered and data on patient inhaler technique, clinical and humanistic outcomes were collected. Outcomes related to professional collaborative relationships were also measured. Discussion Challenges presented included the requirement of significant financial resources for development of study materials and limited availability of validated tools to measure health care professional collaboration over time. PMID:24708800

Development and evaluation of an innovative model of inter-professional education focused on asthma medication use.

PubMed

Bosnic-Anticevich, Sinthia Z; Stuart, Meg; Mackson, Judith; Cvetkovski, Biljana; Sainsbury, Erica; Armour, Carol; Mavritsakis, Sofia; Mendrela, Gosia; Travers-Mason, Pippa; Williamson, Margaret

2014-04-07

Inter-professional learning has been promoted as the solution to many clinical management issues. One such issue is the correct use of asthma inhaler devices. Up to 80% of people with asthma use their inhaler device incorrectly. The implications of this are poor asthma control and quality of life. Correct inhaler technique can be taught, however these educational instructions need to be repeated if correct technique is to be maintained. It is important to maximise the opportunities to deliver this education in primary care. In light of this, it is important to explore how health care providers, in particular pharmacists and general medical practitioners, can work together in delivering inhaler technique education to patients, over time. Therefore, there is a need to develop and evaluate effective inter-professional education, which will address the need to educate patients in the correct use of their inhalers as well as equip health care professionals with skills to engage in collaborative relationships with each other. This mixed methods study involves the development and evaluation of three modules of continuing education, Model 1, Model 2 and Model 3. A fourth group, Model 4, acting as a control.Model 1 consists of face-to-face continuing professional education on asthma inhaler technique, aimed at pharmacists, general medical practitioners and their practice nurses.Model 2 is an electronic online continuing education module based on Model 1 principles.Model 3 is also based on asthma inhaler technique education but employs a learning intervention targeting health care professional relationships and is based on sociocultural theory.This study took the form of a parallel group, repeated measure design. Following the completion of continuing professional education, health care professionals recruited people with asthma and followed them up for 6 months. During this period, inhaler device technique training was delivered and data on patient inhaler technique, clinical and humanistic outcomes were collected. Outcomes related to professional collaborative relationships were also measured. Challenges presented included the requirement of significant financial resources for development of study materials and limited availability of validated tools to measure health care professional collaboration over time.

Air pollution and asthma control in the Epidemiological study on the Genetics and Environment of Asthma

PubMed Central

Jacquemin, Bénédicte; Kauffmann, Francine; Pin, Isabelle; Le Moual, Nicole; Bousquet, Jean; Gormand, Frédéric; Just, Jocelyne; Nadif, Rachel; Pison, Christophe; Vervloet, Daniel; Künzli, Nino; Siroux, Valérie

2012-01-01

Background The associations between exposure to air pollution and asthma control are not well known. The objective is to assess the association between long term exposure to NO2, O3 and PM10 and asthma control in the EGEA2 study (2003–2007). Methods Modeled outdoor NO2, O3 and PM10 estimates were linked to each residential address using the 4-km grid air pollutant surface developed by the French Institute of Environment for 2004. Asthma control was assessed in 481 subjects with current asthma using a multidimensional approach following the 2006–2009 GINA guidelines. Multinomial and ordinal logistic regressions were conducted adjusted on sex, age, BMI, education, smoking and use of inhaled corticosteroids. The association between air pollution and the three domains of asthma control (symptoms, exacerbations and lung function) was assessed. Odds Ratios (ORs) are reported per Inter Quartile Range (IQR). Results Median concentrations (μg.m−3) were 32(IQR 25–38) for NO2 (n=465), 46(41–52) for O3 and 21(18–21) for PM10 (n=481). In total, 44%, 29% and 27% had controlled, partly-controlled and uncontrolled asthma. The ordinal ORs for O3 and PM10 with asthma control were 1.69(95%CI 1.22–2.34) and 1.35(95%CI 1.13–1.64) respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaled corticosteroids, atopy, season of examination or BMI. Both pollutants were associated with each of the three main domains of control. Conclusions The results suggest that long-term exposure to PM10 and O3 is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function. Abstract Word count: 250 Key words: air pollution, asthma, asthma control PMID:21690606

Air pollution and asthma control in the Epidemiological study on the Genetics and Environment of Asthma.

PubMed

Jacquemin, Bénédicte; Kauffmann, Francine; Pin, Isabelle; Le Moual, Nicole; Bousquet, Jean; Gormand, Frédéric; Just, Jocelyne; Nadif, Rachel; Pison, Christophe; Vervloet, Daniel; Künzli, Nino; Siroux, Valérie

2012-09-01

The associations between exposure to air pollution and asthma control are not well known. The objective of this study was to assess the association between long-term exposure to NO(2), O(3) and PM(10) and asthma control in the follow-up of the Epidemiological study on the Genetics and Environment of Asthma (EGEA2) (2003-2007). Modelled outdoor NO(2), O(3) and PM(10) estimates were linked to each residential address using the 4 km grid air pollutant surface developed by the French Institute of Environment in 2004. Asthma control was assessed in 481 subjects with current asthma using a multidimensional approach following the 2006-2009 Global Initiative for Asthma guidelines. Multinomial and ordinal logistic regressions were conducted adjusted for sex, age, body mass index, education, smoking and use of inhaled corticosteroids. The association between air pollution and the three domains of asthma control (symptoms, exacerbations and lung function) was assessed. ORs are reported per IQR. Median concentrations (in micrograms per cubic metre) were 32 (IQR 25-38) for NO(2) (n=465), 46 (41-52) for O(3) and 21 (18-21) for PM(10) (n=481). In total, 44%, 29% and 27% had controlled, partly controlled and uncontrolled asthma, respectively. The ordinal ORs for O(3) and PM(10) with asthma control were 1.69 (95% CI 1.22 to 2.34) and 1.35 (95% CI 1.13 to 1.64), respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaled corticosteroids, atopy, season of examination or body mass index. Both pollutants were associated with each of the three main domains of control. The results suggest that long-term exposure to PM(10) and O(3) is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function.

Models for estimating and projecting global, regional and national prevalence and disease burden of asthma: protocol for a systematic review.

PubMed

Bhuia, Mohammad Romel; Nwaru, Bright I; Weir, Christopher J; Sheikh, Aziz

2017-05-17

Models that have so far been used to estimate and project the prevalence and disease burden of asthma are in most cases inadequately described and irreproducible. We aim systematically to describe and critique the existing models in relation to their strengths, limitations and reproducibility, and to determine the appropriate models for estimating and projecting the prevalence and disease burden of asthma. We will search the following electronic databases to identify relevant literature published from 1980 to 2017: Medline, Embase, WHO Library and Information Services and Web of Science Core Collection. We will identify additional studies by searching the reference list of all the retrieved papers and contacting experts. We will include observational studies that used models for estimating and/or projecting prevalence and disease burden of asthma regarding human population of any age and sex. Two independent reviewers will assess the studies for inclusion and extract data from included papers. Data items will include authors' names, publication year, study aims, data source and time period, study population, asthma outcomes, study methodology, model type, model settings, study variables, methods of model derivation, methods of parameter estimation and/or projection, model fit information, key findings and identified research gaps. A detailed critical narrative synthesis of the models will be undertaken in relation to their strengths, limitations and reproducibility. A quality assessment checklist and scoring framework will be used to determine the appropriate models for estimating and projecting the prevalence anddiseaseburden of asthma. We will not collect any primary data for this review, and hence there is no need for formal National Health Services Research Ethics Committee approval. We will present our findings at scientific conferences and publish the findings in the peer-reviewed scientific journal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effectiveness of a School-based Academic Asthma Health Education and Counseling Program on Fostering Acceptance of Asthma in Older School-age Students with Asthma

PubMed Central

Kintner, Eileen K.; Cook, Gwendolyn; Marti, C. Nathan; Gomes, Melissa; Meeder, Linda; Van Egeren, Laurie A.

2014-01-01

Purpose The purpose was to evaluate the effectiveness of the academic asthma education and counseling SHARP program on fostering psychosocial acceptance of asthma. Design and Methods This was a phase III, two-group, cluster randomized, single-blinded, longitudinal study. Students from grades 4 and 5 (N = 205) with asthma and their caregivers completed surveys at pre-intervention and at 1, 12, and 24 months post-intervention. Analysis involved multilevel modeling. Results All students demonstrated significant improvement in aspects of acceptance; students in SHARP demonstrated significant improvement in openness to sharing and connectedness with teachers over students in the control condition. Practice Implications The SHARP program offers a well-tested, effective program for psychosocial acceptance of asthma, which is welcomed by schools. PMID:25443593

Association Between 17q12-21 Variants and Asthma in Japanese Women: rs11650680 Polymorphism as Potential Genetic Marker for Asthma

PubMed Central

Tanaka, Keiko; Arakawa, Masashi

2014-01-01

Epidemiological evidence on the relationship between single-nucleotide polymorphisms (SNPs) rs7216389 and rs11650680 on chromosome 17q12-21 and asthma is inconsistent. We examined this issue in young adult Japanese women. Case subjects were 202 women who had been diagnosed with asthma by a doctor, while 1290 women without doctor-diagnosed asthma served as control subjects. Adjustments were made for age and the presence of older siblings. There were no significant associations between SNP rs7216389 and asthma. Compared with the CC genotype of SNP rs11650680, the CT genotype, but not the TT genotype, was significantly inversely associated with asthma: the adjusted odds ratio for the CT genotype was 0.67 (95% confidence interval: 0.46–0.96). This inverse relationship was significant in women with late-onset asthma, but not in those with early-onset asthma. Under the dominant model, a significant inverse association was found between rs11650680 and asthma in women without older siblings, but not in those with older siblings; the interaction, however, was not significant. This is the first study to show that the CT genotype of SNP rs11650680 was significantly inversely associated with asthma, especially adult-onset asthma. We could not find evidence for interactions between rs11650680 and older siblings affecting asthma. PMID:24735179

Eotaxin-Rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response.

PubMed

Asosingh, Kewal; Vasanji, Amit; Tipton, Aaron; Queisser, Kimberly; Wanner, Nicholas; Janocha, Allison; Grandon, Deepa; Anand-Apte, Bela; Rothenberg, Marc E; Dweik, Raed; Erzurum, Serpil C

2016-03-01

Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole-lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge and before airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and a murine model of asthma. Ex vivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wild-type mice transplanted with eotaxin-1/2-deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, whereas adoptive transfer of proangiogenic progenitor cells from wild-type mice in an atopic asthma model into the eotaxin-1/2-deficient mice led to angiogenesis and airway inflammation. The findings indicate that Th2-promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation. Copyright © 2016 by The American Association of Immunologists, Inc.

Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

PubMed

Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

2011-08-01

Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. Copyright © 2011 Elsevier B.V. All rights reserved.

Parental psychosocial stress and asthma morbidity in Puerto Rican twins

PubMed Central

Lange, Nancy E.; Bunyavanich, Supinda; Silberg, Judy L.; Canino, Glorisa; Rosner, Bernard A.; Celedón, Juan C.

2010-01-01

Background Little is known about paternal psychosocial factors and childhood asthma. Objective To examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children. Methods Parents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 and again about their child’s asthma at age 3. Fathers were asked about symptoms of post-traumatic stress disorder (PTSD), depression, and anti-social behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood. Results After multivariable adjustment, paternal PTSD symptoms, depression, and anti-social behavior were each associated with increased asthma symptoms at age 1 (e.g., OR =1.08 for each 1-point increase in PTSD score, 95% CI=1.03–1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (OR for each 1-point increase in symptoms=1.16, 95% CI=1.00–1.36]). In an analysis combining 1 and 3 year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma. Conclusions Both paternal and maternal psychosocial factors may influence asthma morbidity in young Puerto Rican children. PMID:21194742

Positive exercise test and obstructive spirometry in young male conscripts associated with persistent asthma 20 years later.

PubMed

Lindström, Irmeli; Suojalehto, Hille; Lindholm, Harri; Pallasaho, Paula; Luukkonen, Ritva; Karjalainen, Jouko; Lauerma, Antti; Karjalainen, Antti

2012-12-01

Asthma often begins in childhood or early adulthood and is a common disease among conscripts. The identification of long-term predictive factors for persistent asthma may lead to improved treatment opportunities and better disease control. Our aim was to study the prognostic factors of the severity of asthma among 40-year-old male conscripts whose asthma began in youth. We studied 119 conscripts who were referred to the Central Military Hospital during 1987-1990 due to asthma and who attended a follow-up visit approximately 20 years later. Asthma severity was evaluated during military service according to the medical records, and 20 years later during a follow-up visit using Global Initiative for Asthma guidelines. We used the results of lung function and allergy tests at baseline as predictors of current persistent asthma. Compared with baseline, asthma was less severe at follow-up: 11.8% of subjects were in remission, 42.0% had intermittent asthma, 10.9% had mild persistent asthma, and 35.3% had moderate/severe persistent asthma (p < .001). In multivariate models, a positive exercise test at baseline yielded an odds ratio (OR) of 3.2 (95% CI 1.0-9.8, p = .046), a decreased FEV1/FVC % predicted an OR of 4.0 (95% CI 1.7-9.3, p = .002), and a decreased FEF50% % predicted an OR of 2.8 (95% CI 1.3-6.4, p = .012) for current persistent asthma. About half of the men had persistent asthma at the 20-year follow-up. Positive exercise tests and obstructive spirometry results were related to the persistence of asthma and may be useful long-term prognostic factors for asthma severity.

Sustainable Benefits of a Community Hospital-Based Paediatric Asthma Clinic.

PubMed

Kuzik, Brian A; Chen, Chee P; Hansen, Miriam J; Montgomery, Paula L

2017-01-01

In 2011, we reported that our paediatric asthma clinic (PAC) appeared to significantly reduce the burden of paediatric asthma in our community. Supported by these results, the PAC underwent a gradual threefold expansion while maintaining the same model of care. We now report on the outcome of that expansion and demonstrate that our PAC continues to significantly reduce the burden of paediatric asthma in our community. As previously, newly enrolled PAC patients continue to show a 12-month reduction in asthma-related emergency department (ED) visits and admissions exceeding 60% and 80%, respectively. This consistent short-term benefit, coupled with clinic expansion, has contributed to a significant improvement in our rate of paediatric asthma-related ED visits or hospitalizations when compared to other Ontario hospitals.

Accessible Modelling of Complexity in Health (AMoCH) and associated data flows: asthma as an exemplar.

PubMed

Liyanage, Harshana; Luzi, Daniela; De Lusignan, Simon; Pecoraro, Fabrizio; McNulty, Richard; Tamburis, Oscar; Krause, Paul; Rigby, Michael; Blair, Mitch

2016-04-18

Background Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1) to describe the data and information flows in clinical practice to information scientists, (2) to compare health systems and care pathways, (3) to understand how clinical cases are recorded in record systems and (4) to model health care business models.Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain.Objective To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar.Method The four steps in our process are:1. Drawing a rich picture, following Checkland's soft systems methodology;2. Constructing data flow diagrams (DFDs);3. Creating Unified Modelling Language (UML) use case diagrams to describe the interaction of the key actors with the system;4. Activity diagrams, either UML activity diagram or business process modelling notation diagram.Results Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding.Conclusions This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of new or confirmed diagnosis.

Variation in conserved non-coding sequences on chromosome 5q andsusceptibility to asthma and atopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng

2005-09-10

Background: Evolutionarily conserved sequences likely havebiological function. Methods: To determine whether variation in conservedsequences in non-coding DNA contributes to risk for human disease, westudied six conserved non-coding elements in the Th2 cytokine cluster onhuman chromosome 5q31 in a large Hutterite pedigree and in samples ofoutbred European American and African American asthma cases and controls.Results: Among six conserved non-coding elements (>100 bp,>70percent identity; human-mouse comparison), we identified one singlenucleotide polymorphism (SNP) in each of two conserved elements and sixSNPs in the flanking regions of three conserved elements. We genotypedour samples for four of these SNPs and an additional three SNPs eachmore » inthe IL13 and IL4 genes. While there was only modest evidence forassociation with single SNPs in the Hutterite and European Americansamples (P<0.05), there were highly significant associations inEuropean Americans between asthma and haplotypes comprised of SNPs in theIL4 gene (P<0.001), including a SNP in a conserved non-codingelement. Furthermore, variation in the IL13 gene was strongly associatedwith total IgE (P = 0.00022) and allergic sensitization to mold allergens(P = 0.00076) in the Hutterites, and more modestly associated withsensitization to molds in the European Americans and African Americans (P<0.01). Conclusion: These results indicate that there is overalllittle variation in the conserved non-coding elements on 5q31, butvariation in IL4 and IL13, including possibly one SNP in a conservedelement, influence asthma and atopic phenotypes in diversepopulations.« less

Family Relational Factors in Pediatric Depression and Asthma: Pathways of Effect

ERIC Educational Resources Information Center

Wood, Beatrice L.; Miller, Bruce D.; Lim, Jungha; Lillis, Kathleen; Ballow, Mark; Stern, Trudy; Simmens, Samuel

2006-01-01

Objective: This study tested a multilevel biobehavioral family model proposing that negative family emotional climate contributes to child depressive symptoms, which in turn contribute to asthma disease severity. Parent-child relational insecurity is proposed as a mediator. Method: Children with asthma (N = 112; ages 7-18; 55% male) reported…

Oroxylin A Inhibits Allergic Airway Inflammation in Ovalbumin (OVA)-Induced Asthma Murine Model.

PubMed

Zhou, De-Gang; Diao, Bao-Zhong; Zhou, Wen; Feng, Jia-Long

2016-04-01

Oroxylin A, a natural flavonoid isolated from the medicinal herb Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory property. In this study, we aimed to investigate the protective effects and mechanism of oroxylin A on allergic inflammation in OVA-induced asthma murine model. BABL/c mice were sensitized and airway-challenged with OVA to induce asthma. Oroxylin A (15, 30, and 60 mg/kg) was administered by oral gavage 1 h before the OVA treatment on day 21 to 23. The results showed that oroxylin A attenuated OVA-induced lung histopathologic changes, airway hyperresponsiveness, and the number of inflammatory cells. Oroxylin A also inhibited the levels of IL-4, IL-5, IL-13, and OVA-specific IgE in BALF. Furthermore, oroxylin A significantly inhibited OVA-induced NF-κB activation. In conclusion, these results suggested that oroxylin A inhibited airway inflammation in OVA-induced asthma murine model by inhibiting NF-κB activation. These results suggested that oroxylin A was a potential therapeutic drug for treating allergic asthma.

Air pollution and hospital admissions for asthma in a tropical city: Kaohsiung, Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shang-Shyue Tsai; Meng-Hsuan Cheng; Hui-Fen Chiu

2006-07-15

This study was undertaken to determine whether there is an association between air pollutants levels and hospital admissions for asthma in Kaohsiung, Taiwan. Hospital admissions for asthma and ambient air pollution data for Kaohsiung were obtained for the period from 1996 through 2003. The relative risk of hospital admission was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days ({>=}25{sup o}C) statistically significant positive associations were found in all pollutants except sulfur dioxide. On cool days ({<=} 25{sup o}C) all pollutants were significantly associatedmore » with asthma admissions. For the two pollutant models, CO and O{sub 3} were significant in combination with each of the other four pollutants on warm days. On cool days NO{sub 2} remained statistically significant in all the two-pollutant models. This study provides evidence that higher levels of ambient pollutants increase the risk of hospital admissions for asthma.« less

Hormonal factors and incident asthma and allergic rhinitis during puberty in girls.

PubMed

Wei, Junxiang; Gerlich, Jessica; Genuneit, Jon; Nowak, Dennis; Vogelberg, Christian; von Mutius, Erika; Radon, Katja

2015-07-01

Accumulating evidence is indicating that hormonal factors play a role in new-onset allergic rhinitis and asthma after puberty. To determine whether age at menarche and use of hormonal contraceptives predict new-onset allergic rhinitis and asthma after puberty in young German women. A prospective community-based cohort study followed 1,191 girls 9 to 11 years old to early adulthood (19-24 years old). Self-administrated questionnaires concerning age at menarche, use of hormonal contraceptives, and status and age at onset of physician-diagnosed allergic rhinitis and asthma were collected at 16 to 18 and 19 to 24 years of age. Logistic regression models were used to analyze the incidence of asthma and allergic rhinitis after puberty and pooled estimates were obtained from the final model. Eleven percent of girls developed allergic rhinitis after menarche and 3% reported new-onset asthma. Late menarche (>13 years of age) was statistically significantly inversely related to allergic rhinitis (adjusted odds ratio [OR] 0.32, 95% confidence interval [CI] 0.14-0.74) but did not reach the level of statistical significance for asthma (OR 0.32, 95% CI 0.07-1.42). Use of hormonal contraceptives was inversely associated with new-onset allergic rhinitis (OR 0.14, 95% CI 0.08-0.23) and asthma (OR 0.27, 95% CI 0.12-0.58) after puberty. This study shows that girls with late onset of menarche are less likely to develop allergic rhinitis after puberty compared with those who have menarche at an average age. These findings also suggest that, in addition to endogenous hormones, hormonal contraceptives play a role and might protect young women from allergies and asthma. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Individual factors, neighborhood social context and asthma at age 5 years.

PubMed

Vo, Phuong; Bair-Merritt, Megan; Camargo, Carlos A; Eisenberg, Staci; Long, Webb

2017-04-01

Childhood asthma is a major public health problem and its development is multifactorial. We examined whether neighborhood cohesion and disorder were associated with caregiver-report of asthma at age 5 years. This study is a secondary data analysis of the 2011-2012 United States National Survey of Children's Health. Data were available for 4680 children, age 5 years old born at term or preterm with birthweight >2500 g. Neighborhood disorder and cohesion were assessed based on caregivers' responses to validated questionnaires. Child asthma diagnosis was reported by the caregiver. Multivariable logistic regression was used to examine the relationship between these neighborhood factors and caregiver-report of child asthma, while accounting for individual level covariates. Approximately two-thirds of the 4680 children were White and lived in households with income >400% of federal poverty line. Asthma was present in 399 (9%) children. Child female sex was associated with reduced risk of caregiver-reported asthma while non-Hispanic Black race and having smokers in the household were independently associated with increased risk in multivariable models. In these models, neighborhood disorder was significantly associated with asthma (adjusted Odds Ratio [aOR] 1.70, 95% Confidence Interval [CI] 1.04-2.78), while neighborhood cohesion was not (aOR 0.93, 95% CI 0.51-1.68). Even after adjustment for several individual level factors, neighborhood disorder was associated with caregiver-report of asthma in this nationally representative sample of 5-year-old children. Further research is needed to better understand how risk factors at different levels of the socio-ecological framework may interact to affect childhood asthma development.

An integrated operational definition and conceptual model of asthma self-management in teens.

PubMed

Mammen, Jennifer; Rhee, Hyekyun; Norton, Sally A; Butz, Arlene M; Halterman, Jill S; Arcoleo, Kimberly

2018-01-19

A previous definition of adolescent asthma self-management was derived from interviews with clinicians/researchers and published literature; however, it did not incorporate perspectives of teens or parents. Therefore, we conducted in-depth interviews with teens and parents and synthesized present findings with the prior analysis to develop a more encompassing definition and model. Focal concepts were qualitatively extracted from 14-day self-management voice-diaries (n = 14) and 1-hour interviews (n = 42) with teens and parents (28 individuals) along with concepts found in the previous clinical/research oriented analysis. Conceptual structure and relationships were identified and key findings synthesized to develop a revised definition and model of adolescent asthma self-management. There were two primary self-management constructs: processes of self-management and tasks of self-management. Self-management was defined as the iterative process of assessing, deciding, and responding to specific situations in order to achieve personally important outcomes. Clinically relevant asthma self-management tasks included monitoring asthma, managing active issues through pharmacologic and non-pharmacologic strategies, preventing future issues, and communicating with others as needed. Self-management processes were reciprocally influenced by intrapersonal factors (both cognitive and physical), interpersonal factors (family, social and physical environments), and personally relevant asthma and non-asthma outcomes. This is the first definition of asthma self-management incorporating teen, parent, clinician, and researcher perspectives, which suggests that self-management processes and behaviors are influenced by individually variable personal and interpersonal factors, and are driven by personally important outcomes. Clinicians and researchers should investigate teens' symptom perceptions, medication beliefs, current approaches to symptom management, relevant outcomes, and personal priorities.

Ethnic variations in incidence of asthma episodes in England & Wales: national study of 502,482 patients in primary care.

PubMed

Netuveli, Gopalakrishnan; Hurwitz, Brian; Sheikh, Aziz

2005-10-21

Recent studies have demonstrated marked international variations in the prevalence of asthma, but less is known about ethnic variations in asthma epidemiology within individual countries and in particular the impact of migration on risk of developing asthma. Recent within country comparisons have however revealed that despite originating from areas of the world with a low risk for developing asthma, South Asian and Afro-Caribbean people in the UK are significantly (3x and 2x respectively) more likely to be admitted to hospital for asthma related problems than Whites. Using data from the Fourth National Study of Morbidity Statistics in General Practice, a one-percent broadly representative prospective cohort study of consultations in general practice, we investigated ethnic variations in incident asthma consultations (defined as new or first consultations), and compared consultation rates between those born inside and outside the UK (migrant status). Logistic regression models were used to examine the combined effects of ethnicity and migration on asthma incident consultations. Results showed significantly lower new/first asthma consultation rates for Whites than for each of the ethnic minority groups studied (mean age-adjusted consultation rates per 1000 patient-years: Whites 26.4 (95%CI 26.4, 26.4); South Asians 30.4 (95%CI 30.3, 30.5); Afro-Caribbeans 35.1 (95%CI 34.9, 35.3); and Others 27.8 (27.7, 28.0). Within each of these ethnic groups, those born outside of the UK showed consistently lower rates of incident asthma consultations. Modelling the combined effects of ethnic and migrant status revealed that UK-born South Asians and Afro-Caribbeans experienced comparable risks for incident GP consultations for asthma to UK-born Whites. Non-UK born Whites however experienced reduced risks (adjusted OR 0.82, 95%CI 0.69, 0.97) whilst non-UK born South Asians experienced increased risks (adjusted OR 1.33, 95%CI 1.04, 1.70) compared to UK-born Whites. These findings strongly suggest that ethnicity and migration have significant and independent effects on asthma incidence. The known poorer asthma outcomes in UK South Asians and Afro-Caribbeans may in part be explained by the offspring of migrants experiencing an increased risk of developing asthma when compared to UK-born Whites. This is the first study to find heterogeneity for incident asthma consultations in Whites by migrant status.

Asthma prevalence and school-related hazardous air pollutants in the US-México border area.

PubMed

Carrillo, Genny; Perez Patron, Maria J; Johnson, Natalie; Zhong, Yan; Lucio, Rose; Xu, Xiaohui

2018-04-01

Asthma is the most common chronic disease in children and has been linked to high levels of ambient air pollution and certain hazardous air pollutants (HAPs). Outdoor pollutants such as benzene, released by car emissions, and organic chemicals found in diesel exhaust, as well as particles and irritant gases, including nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and ozone (O 3 ), contribute to an increased prevalence of respiratory diseases such as asthma. The objectives of this study were to: 1) conduct a screening survey to identify high risk for asthma among school-age children in Hidalgo County, and, 2) study the potential health impact of school-related exposure to HAPs pertaining to asthma risk. We carried out a quantitative cross-sectional study combining a school-based asthma screening survey across 198 schools in Hidalgo County, Texas, with information on school neighborhood environments, including census tract-level information on hazardous air pollutants (HAPs) and socioeconomic status (SES) in the respective school neighborhoods. HAPs levels were assessed based on the EPA 2011 National-Scale Air Toxics Assessment (NATA) while SES information was assessed using data from the 2010-2014 American Community Survey. 2930 students completed the asthma screening survey and results showed an overall asthma prevalence of 9.4%, slightly higher than the national and state prevalence. Participants in the 14-18 years old age group showed a much higher asthma prevalence of 16.7%. When assessing school-neighborhood characteristics, our results revealed no significant differences in asthma prevalence across census tracts with different SES levels. For HAPs, in the single-pollutant model, chlorine levels showed a significant linear trend for prevalence of asthma (p=0.03) while hydrochloric acid had a marginally significant linear trend (p=0.08). The association with chlorine remained significant in the multi-pollutant model. Asthma prevalence among school-age children in Hidalgo County, Texas, is 9.4%, which is slightly higher than the state rate, especially among young adults, ages 14-18 years who had an asthma rate of 16.7%. Results support an association between exposures to school-neighborhood HAPs and risk for pediatric asthma, especially as related to chlorine. No significant effects of school-level SES on asthma risk were observed. Published by Elsevier Inc.

Race and asthma control in the pediatric population of Hawaii.

PubMed

Wu, Brian H; Cabana, Michael D; Hilton, Joan F; Ly, Ngoc P

2011-05-01

The racially unique population of Hawaii has one of the highest prevalences of childhood asthma in America. We estimate the prevalence of impaired asthma control among asthmatic children in Hawaii and determine which factors are associated with impaired control. We analyzed data from 477 asthmatic children living in Hawaii participating in the 2006-2008 Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Surveys. Impaired asthma control was modeled after 2007 National Asthma Education and Prevention Program guidelines. Univariate and multivariate analyses were used to identify factors associated with impaired asthma control. Children (53.8%) with asthma were either part or full Native Hawaiian/Pacific Islander. While 35.6% of asthmatic children met criteria for impaired asthma control, being part or full Native Hawaiian/Pacific Islander was not associated with impaired control. Only 31.1% of children with impaired control reported the use of inhaled corticosteroids despite >80% having had a routine checkup for asthma in the past year and receipt of asthma education from a healthcare provider. A large proportion of asthmatic children in Hawaii have impaired asthma control that does not appear to be associated with race but may be associated with inadequate pharmacologic therapy. While a significant percentage reported receiving routine asthma care and asthma education, a minority reported using inhaled corticosteroids. Reasons for this discrepancy between asthma assessment and treatment are unclear. However, additional education on part of the physician, community, and healthcare system are likely to improve management and reduce morbidity in this population. Copyright © 2010 Wiley-Liss, Inc.

Human dendritic cells in the severe combined immunodeficiency mouse model: their potentiating role in the allergic reaction.

PubMed

Hammad, H; Duez, C; Fahy, O; Tsicopoulos, A; André, C; Wallaert, B; Lebecque, S; Tonnel, A B; Pestel, J

2000-04-01

Dendritic cells (DCs) are present in the lungs and airways of healthy and allergic subjects where they are exposed to inhaled antigens. After the uptake of antigens, DCs migrate to lymphoid organs where T cells initiate and control the immune response. The migratory properties of DCs are an essential component of their function but remain unclear in the situation of allergic diseases. To better understand the role of DCs in response to allergens, we first investigated their presence in an original experimental model of allergic asthma: the humanized severe combined immunodeficiency (SCID) mouse reconstituted with peripheral blood mononuclear cells from patients sensitive to Dermatophagoides pteronyssinus (Dpt). Human DCs were detected in lungs of mice developing an inflammatory pulmonary infiltrate and appeared to be mainly located in the alveolar spaces. In a second step, human DCs were generated in vitro from monocytes and injected into naive SCID mice exposed or not exposed to Dpt aerosols. Their migratory behavior was explored, as well as their potential role in modulating the IgE production after exposure to Dpt. After exposure to Dpt, the number of DCs present in airways decreased, while it increased into the spleen and thymus of the mice. The IgE production increased in the presence of DCs as compared with mice not injected with DCs. These results suggest that DCs may play a role in the pulmonary allergic reaction developed in response to Dpt in SCID mice.

Household Food Insecurity is Associated with Childhood Asthma.

PubMed

Mangini, Lauren D; Hayward, Mark D; Dong, Yong Quan; Forman, Michele R

2015-12-01

In 2013, 20% of U.S. households with children experienced food insecurity. Asthma afflicts over 7 million children; prevalence has steadily increased while incidence peaks in young children. Asthma and food insecurity share the determinants of poverty and race that are associated with weight, yet limited research on the relation between food insecurity and asthma exists. The objective of this study was to determine the association between food insecurity and asthma in a diverse sample of children. Cross-sectional data from grade 3 of the Early Childhood Longitudinal Study-Kindergarten Cohort were analyzed (n = 11,099). Food security based on the USDA module and asthma diagnosis were reported by parents; anthropometric factors were measured. Multivariate logistic regression models of food security and asthma were analyzed overall and by race/ethnicity. Children in food-insecure households had a 4% higher adjusted odds of asthma (95% CI: 1.02, 1.06). Adjusted odds of asthma were also higher by 70% for males (95% CI: 1.69, 1.71), 53% for non-Hispanic black (NHB) children (95% CI: 1.51, 1.54), 20% for Hispanic children (95% CI: 1.19, 1.21), 38% for overweight children (95% CI: 1.36, 1.39), 67% for obese children (95% CI: 1.65, 1.68), 23% for low-birth weight children (95% CI: 1.21, 1.24), 24% if mothers had a high school diploma (95% CI: 1.23, 1.26), and 33% if mothers had some college education (95% CI: 1.32, 1.35). High-birth weight children (OR: 0.84; 95% CI: 0.83, 0.85) and those with foreign-born mothers (OR: 0.52; 95% CI: 0.51, 0.53) had lower odds of asthma. Being food-insecure remained positively associated with asthma in non-Hispanic whites and Hispanics but was inversely associated with odds among NHBs. Odds of asthma doubled (OR: 2.00; 95% CI: 1.97, 2.03) for all children in households that were both food-insecure and poor; this relation remained positive in race/ethnicity-specific models. Food insecurity is positively associated with asthma in U.S. third graders, and household poverty strengthens the association. © 2015 American Society for Nutrition.

Modeling of Regional Climate Change Effects on Ground-Level Ozone and Childhood Asthma

PubMed Central

Sheffield, Perry E.; Knowlton, Kim; Carr, Jessie L.; Kinney, Patrick L.

2011-01-01

Background The adverse respiratory effects of ground-level ozone are well-established. Ozone is the air pollutant most consistently projected to increase under future climate change. Purpose To project future pediatric asthma emergency department visits associated with ground-level ozone changes, comparing 1990s to 2020s. Methods This study assessed future numbers of asthma emergency department visits for children aged 0–17 years using (1) baseline New York City metropolitan area emergency department rates, (2) a dose–response relationship between ozone levels and pediatric asthma emergency department visits, and (3) projected daily 8-hour maximum ozone concentrations for the 2020s as simulated by a global-to-regional climate change and atmospheric chemistry model. Sensitivity analyses included population projections and ozone precursor changes. This analysis occurred in 2010. Results In this model, climate change could cause an increase in regional summer ozone-related asthma emergency department visits for children aged 0–17 years of 7.3% across the New York City metropolitan region by the 2020s. This effect diminished with inclusion of ozone precursor changes. When population growth is included, the projections of morbidity related to ozone are even larger. Conclusions The results of this analysis demonstrate that the use of regional climate and atmospheric chemistry models make possible the projection of local climate change health effects for specific age groups and specific disease outcomes – such as emergency department visits for asthma. Efforts should be made to improve on this type of modeling to inform local and wider-scale climate change mitigation and adaptation policy. PMID:21855738

Pregnancy diet and offspring asthma risk over a 10-year period: the Lifeways Cross Generation Cohort Study, Ireland.

PubMed

Viljoen, Karien; Segurado, Ricardo; O'Brien, John; Murrin, Celine; Mehegan, John; Kelleher, Cecily C

2018-02-20

The association of maternal pregnancy diet with offspring asthma risk have been reported. However, literature on longitudinal patterns of asthma risk relative to intrauterine nutrient exposure is limited. We aimed to establish whether vegetable, oily fish and vitamin D intake during pregnancy are associated with childhood asthma risk over a 10-year period in the Irish Republic. Mother-child pairs (n=897) from the Lifeways prospective birth cohort, with data on nutrient intake during pregnancy and asthma status, respectively, were eligible for inclusion in the analysis. Data on socioeconomic and morbidity indicators over 10 years of follow-up on mothers and the index child were collected through self-administered questionnaires. Asthma status as diagnosed by the general practitioner at any time point over 10 years was related to maternal vegetable, oily fish and vitamin D intake during pregnancy, while adjusting for gestational age, socioeconomic status, smoking at delivery, breast feeding, season of birth and supplement use. Data were modelled with a marginal model on correlated observations over time within individuals. In the fully adjusted model, asthma was inversely associated with higher daily average intake of oily fish (OR 0.23 per serving/day, 95% CI 0.04 to 1.41) and of vegetables (OR 0.96 per serving/day, 95% CI 0.88 to 1.05), but the confidence limits overlapped 1. A higher daily vitamin D intake was associated with reduced odds of asthma (OR 0.93 per μg/day, 95% CI 0.89 to 0.98). This analysis suggests higher daily average intake of vitamin D in pregnancy is associated with asthma risk in offspring over the first 10 years of life. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao

Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2 weeks. 48 h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocytemore » count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. - Highlights: • Diminazene aceturate (DIZE), an ACE2 activator prevents ovalbumin-induced asthma. • DIZE acted by upregulating ACE2, downregulating ACE1, MAPKs, markers of inflammation, apoptosis. • DIZE reduced airway inflammation, fibrosis, right ventricular hypertrophy and restored airway responsiveness.« less

Pathways linking health literacy, health beliefs, and cognition to medication adherence in older adults with asthma.

PubMed

Soones, Tacara N; Lin, Jenny L; Wolf, Michael S; O'Conor, Rachel; Martynenko, Melissa; Wisnivesky, Juan P; Federman, Alex D

2017-03-01

Limited health literacy is associated with low adherence to asthma controller medications among older adults. We sought to describe the causal pathway linking health literacy to medication adherence by modeling asthma illness and medication beliefs as mediators. We recruited adults aged 60 years and older with asthma from hospital and community practices in New York, New York, and Chicago, Illinois. We measured health literacy and medication adherence using the Short Test of Functional Health Literacy in Adults and the Medication Adherence Rating Scale, respectively. We used validated instruments to assess asthma illness and medication beliefs. We assessed cognition using a cognitive battery. Using structural equation modeling, we modeled illness and medication beliefs as mediators of the relationship between health literacy and adherence while controlling for cognition. Our study included 433 patients with a mean age of 67 ± 6.8 years. The sample had 84% women, 31% non-Hispanic blacks, and 39% Hispanics. The 36% of patients with limited health literacy were more likely to have misconceptions about asthma (P < .001) and asthma medications (P < .001). Health literacy had a direct effect (β = 0.089; P < .001) as well as an indirect effect on adherence mediated by medications concerns (β = 0.033; P = .002). Neither medication necessity (β = 0.044; P = .138) nor illness beliefs (β = 0.007; P = .143) demonstrated a mediational role between health literacy and adherence. Interventions designed to improve asthma controller medication adherence in older adults may be enhanced by addressing concerns about medications in addition to using communication strategies appropriate for populations with limited health literacy and cognitive impairments. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Drawing asthma: An exploration of patients' perceptions and experiences.

PubMed

Cheung, Melissa Mei Yin; Saini, Bandana; Smith, Lorraine

2018-03-01

As an art form, drawings can facilitate the tangible expression of patients' inner images and feelings in a range of health conditions. However, there are currently no published studies investigating adults' perspectives of asthma using drawings. This study aimed to explore how adults' drawings illustrate their perceptions and experiences of asthma. Adults with asthma participated in a one-on-one drawing activity. Analysis was grounded in the participants' accounts of their drawing, which were examined alongside the relevant image. A coding approach was used to cluster thematic material and map the data according to the Common-Sense Model of Self-Regulation (CSM). Eighteen participants took part. Three themes emerged: (1) asthma is constrictive and restrictive, (2) feeling alone, feeling different, and (3) the life journey of asthma. The drawings aligned with several domains of the CSM, in particular consequences. The images drawn by the participants and their subsequent discussions highlighted the prominence of the emotional burden of asthma. The drawings provided powerful and evocative communication of the experience of asthma. Future research using drawings can further both healthcare professionals' and patients' understanding of the physical, social and emotional demands of living with asthma, and support the development of asthma self-management practices.

The asthma knowledge and perceptions of older Australian adults: implications for social marketing campaigns.

PubMed

Evers, Uwana; Jones, Sandra C; Caputi, Peter; Iverson, Don

2013-06-01

The purpose of this research is to gain an understanding of the asthma perceptions of older adults and identify gaps in their asthma knowledge. In regional New South Wales, Australia, a stratified, random sample of 4066 adults, aged 55 years and over, both with and without an asthma diagnosis, completed a survey based on the Health Belief Model about asthma knowledge and perceptions. Almost half of the sample had experienced symptoms of breathlessness in the past four weeks. Breathlessness was a predictor of lower health ratings and poorer mood. Older adults reported low susceptibility to developing asthma. The sample demonstrated poor knowledge of key asthma symptoms including shortness of breath, tightness in the chest and a cough at night. There is a general lack of asthma awareness in this age group. This could result in not seeking medical help, and thus a reduced quality of life. Older adults should be made aware of key symptoms and the prevalence of asthma in the older adult population, and be empowered to take control of their respiratory health. Audience segmentation for an intervention should be based on recent experience of breathlessness and asthma diagnosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A preliminary study to evaluate a patient-centred asthma education programme on parental control of home environment and asthma signs and symptoms in children with moderate-to-severe asthma.

PubMed

Tzeng, Li-Fen; Chiang, Li-Chi; Hsueh, Kai-Chung; Ma, Wei-Fen; Fu, Lin-Shien

2010-05-01

To evaluate the effectiveness of a nurse-led patient-centred asthma education programme on home environmental control behaviours of parents of children with moderate or severe asthma. Reducing allergic triggers is important self-management behaviour for preventing asthma attacks and patient-centred asthma education has been shown to effectively manage chronic disease. A preliminary quasi-experimental, non-equivalent control group design was used. Dyads (n = 75) of parents and their children with moderate or severe asthma (ages 6-14 years) were purposively recruited from the asthma clinics of two hospitals in central Taiwan. The experimental group of 38 children/parents from one hospital received patient-centred asthma education. The comparison group of 37 children/parents from the other hospital received routine individual education. At pretest and at the end of the three-month patient-centred asthma education programme, we measured parents' control of home environmental triggers, children's asthma signs/symptoms and children's pulmonary function. Data were analysed by the general linear model for repeat measures. The level of improvement in dust and cleaning methods was significantly greater among parents in the experimental group than among those in the comparison group (p < 0.05). Children with moderate or severe asthma in the experimental group had fewer signs/symptoms of asthma and better lung function than children in the comparison group. Our patient-centred asthma education programme improved parents' home environmental control and children's asthma sign/symptoms and lung function. Nurses can play primary roles as patient educators in asthma clinics. Well-trained patient educators can continuously monitor self-management behaviours to improve patients' compliance with home environmental control, thus leading to better physical outcomes in children with asthma than routine individual asthma education alone.

State-level medical and absenteeism cost of asthma in the United States.

PubMed

Nurmagambetov, Tursynbek; Khavjou, Olga; Murphy, Louise; Orenstein, Diane

2017-05-01

For medically treated asthma, we estimated prevalence, medical and absenteeism costs, and projected medical costs from 2015 to 2020 for the entire population and separately for children in the 50 US states and District of Columbia (DC) using the most recently available data. We used multiple data sources, including the Medical Expenditure Panel Survey, U.S. Census Bureau, Kaiser Family Foundation, Medical Statistical Information System, and Current Population Survey. We used a two-part regression model to estimate annual medical costs of asthma and a negative binomial model to estimate annual school and work days missed due to asthma. Per capita medical costs of asthma ranged from $1,860 (Mississippi) to $2,514 (Michigan). Total medical costs of asthma ranged from $60.7 million (Wyoming) to $3.4 billion (California). Medicaid costs ranged from $4.1 million (Wyoming) to $566.8 million (California), Medicare from $5.9 million (DC) to $446.6 million (California), and costs paid by private insurers ranged from $27.2 million (DC) to $1.4 billion (California). Total annual school and work days lost due to asthma ranged from 22.4 thousand (Wyoming) to 1.5 million days (California) and absenteeism costs ranged from $4.4 million (Wyoming) to $345 million (California). Projected increase in medical costs from 2015 to 2020 ranged from 9% (DC) to 34% (Arizona). Medical and absenteeism costs of asthma represent a significant economic burden for states and these costs are expected to rise. Our study results emphasize the urgency for strategies to strengthen state level efforts to prevent and control asthma attacks.

Xerostomia relates to the degree of asthma control.

PubMed

Alcázar Navarrete, Bernardino; Gómez-Moreno, Gerardo; Aguilar-Salvatierra, Antonio; Guardia, Javier; Romero Palacios, Pedro José

2015-04-01

Few studies have assessed the relationships between xerostomia and the use of inhaled corticosteroids (ICS). The main objective of this study was to investigate the prevalence of xerostomia in a respiratory outpatient clinic and its relationship with bronchial asthma and ICS use. A cross-sectional observational study of patients recruited in an outpatient setting divided them according to previous diagnoses of bronchial asthma. Data about pulmonary function, concomitant medication, medical comorbidities, Xerostomia Inventory test (XI test), and the degree of asthma control by ACT (asthma control test) were collected for each patient. A linear regression model was applied, using the XI score as dependent variable and the ACT score as independent variable. The 57 patients were divided into asthmatics (40 patients, 70.2%) and control group without asthma (17, 29.8%). The prevalence of xerostomia was 87.7% (50 patients), with no differences between the study groups or current dose of ICS. In the asthmatic group, patients with uncontrolled asthma had worse XI scores than those with partially or totally controlled asthma (30.43 ± 8.71 vs. 24.92 ± 8.08; P < 0.05). In a logistic regression model, the XI test was significantly associated to ACT scores with a moderately strong correlation (r = 0.55; P = 0.005) after adjusting for the current daily dose of ICS. Xerostomia is a common symptom in the ambulatory setting. There is a moderate relationship between the degree of asthma control and the severity of xerostomia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Is asthma associated with cognitive impairments? A meta-analytic review.

PubMed

Irani, Farzin; Barbone, Jordan Mark; Beausoleil, Janet; Gerald, Lynn

2017-12-01

Asthma is a chronic disease with significant health burden and socioeconomic and racial/ethnic disparities related to diagnosis and treatment. Asthma primarily affects the lungs, but can impact brain function through direct and indirect mechanisms. Some studies have suggested that asthma negatively impacts cognition, while others have failed to identify asthma-related cognitive compromise. We aimed to conduct a meta-analysis of cognition in individuals with asthma compared to that in healthy controls. We also examined the impact of some key potential moderators. Data on cognitive outcome measures and sociodemographic, illness-related, and study-related variables were extracted from studies reporting cognitive test performance in individuals with asthma compared to that in controls. There was no evidence of publication bias. A random-effects model examining differences in task performance between 2017 individuals with asthma and 2131 healthy controls showed significant effects in the small to medium range. Cognitive deficits associated with asthma were global, with strongest effects on broader measures involving academic achievement and executive functioning, but with additional impact on processing speed, global intellect, attention, visuospatial functioning, language, learning, and memory. Severity of asthma was a key moderator, with greatest cognitive deficits associated with severe asthma. Cognitive burden was also greatest in asthma patients who were younger, males, from low socioeconomic backgrounds, and from racial/ethnic minorities. Effects were independent of type of population (child versus adult), type of study (norm-referenced versus control-referenced), or reported use of oral or inhaled corticosteroid medications. There is cognitive burden associated with asthma, particularly among vulnerable groups with severe asthma. This could be due to increased risk of intermittent cerebral hypoxia in severe asthma. The clinical need to assess cognition in individuals with asthma is underscored.

Occupational exposures associated with severe exacerbation of asthma.

PubMed

Henneberger, P K; Liang, X; Lillienberg, L; Dahlman-Höglund, A; Torén, K; Andersson, E

2015-02-01

The exacerbation of asthma by workplace conditions is common, but little is known about which agents pose a risk. We used data from an existing survey of adults with asthma to identify occupational exposures associated with severe exacerbation of asthma. Questionnaires were completed by 557 working adults with asthma. Severe exacerbation of asthma in the past 12 months was defined as asthma-related hospitalization, or reports of both unplanned asthma care and treatment with a short course of oral corticosteroids. Occupational exposures for the same time period were assessed using an asthma-specific job exposure matrix. We modeled severe exacerbation to yield prevalence ratios (PRs) for exposures while controlling for potential confounders. A total of 164 participants (29%) were positive for severe exacerbation, and 227 (40.8%) were assessed as being exposed to asthma agents at work. Elevated PRs were observed for several specific agents, notably the irritant subcategories of environmental tobacco smoke (PR 1.84, 95%CI 1.34-2.51) among all participants, inorganic dusts (PR 2.53, 95%CI 1.37-4.67) among men, and the low molecular weight subcategory of other highly reactive agents (PR 1.97, 95%CI 1.08-3.60) among women. Among working adults with asthma, severe exacerbation was associated with several occupational agents.

Predicting worsening asthma control following the common cold

PubMed Central

Walter, Michael J.; Castro, Mario; Kunselman, Susan J.; Chinchilli, Vernon M; Reno, Melissa; Ramkumar, Thiruvamoor P.; Avila, Pedro C.; Boushey, Homer A.; Ameredes, Bill T.; Bleecker, Eugene R.; Calhoun, William J.; Cherniack, Reuben M.; Craig, Timothy J.; Denlinger, Loren C.; Israel, Elliot; Fahy, John V.; Jarjour, Nizar N.; Kraft, Monica; Lazarus, Stephen C.; Lemanske, Robert F.; Martin, Richard J.; Peters, Stephen P.; Ramsdell, Joe W.; Sorkness, Christine A.; Rand Sutherland, E.; Szefler, Stanley J.; Wasserman, Stephen I.; Wechsler, Michael E.

2008-01-01

The asthmatic response to the common cold is highly variable and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multi-center cohort study of 413 adult subjects with asthma, we used the mini-Asthma Control Questionnaire (mini-ACQ) to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models examined demographic, physiologic, serologic, and cold-related characteristics for their relationship to changes in asthma control following a cold. We observed a clinically significant worsening of asthma control following a cold (increase in mini-ACQ of 0.69 ± 0.93). Univariate analysis demonstrated season, center location, cold length, and cold severity measurements all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed the day 2 and the cumulative sum of the day 1 and 2 WURSS-21 scores were significant predictors for the subsequent changes in asthma control. In asthmatic subjects the cold severity measured within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold. PMID:18768579

Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

PubMed

Kamalaldin, N A; Sulaiman, S A; Yusop, M R; Yahaya, B

2017-01-01

Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO) is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma.

Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

PubMed Central

Sulaiman, S. A.

2017-01-01

Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO) is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma. PMID:28660089

Investigating the associations between Mediterranean diet, physical activity and living environment with childhood asthma using path analysis.

PubMed

Alphantonogeorgos, George; Panagiotakos, Demosthenes B; Grigoropoulou, Dimitra; Yfanti, Konstantina; Papoutsakis, Constantina; Papadimitriou, Anastasios; Anthracopoulos, Michael B; Bakoula, Chryssa; Priftis, Kostas N

2014-01-01

To investigate the role of the Mediterranean diet and physical activity with relation to living environment and childhood asthma. 1125 children (529 boys), 10 to 12 years old were recruited either in an urban environment (Athens, n = 700) or rural environment (n = 425) in Greece. A path analytic model was developed to assess the causal relation between urban environment and asthma prevalence (standardized ISAAC questionnaire), through the mediation of the Mediterranean diet (evaluated by the KIDMED food frequency questionnaire) and physical activity (evaluated by the PALQ physical activity questionnaire). The proposed model had a very good fit (χ2/df ratio =1.05, RMSEA=0.007, 90% confidence interval: 0.01 to 0.046, p=0.97, CFI = 0.98). A significant total positive effect was found between urban environment and asthma symptoms (standardized beta= 0.09, p<0.001). Adherence to the Mediterranean diet was related negatively with asthma symptoms (standardized beta = -0.224, p<0.001). An inverse mediating effect of the Mediterranean diet was observed for the urban environment - asthma relation (standardized beta=-0.029, p<0.001) while physical activity had no significant contribution (p=0.62), adjusted for several confounders. The Mediterranean diet may protect against the harmful effect of urban environment on childhood asthma.

Childhood Epilepsy and Asthma: A Test of an Extension of the Double ABCX Model.

ERIC Educational Resources Information Center

Austin, Joan Kessner

The Double ABCX Model of Family Adjustment and Adaptation, a model that predicts adaptation to chronic stressors on the family, was extended by dividing it into attitudes, coping, and adaptation of parents and child separately, and by including variables relevant to child adaptation to epilepsy or asthma. The extended model was tested on 246…

Allergen challenge-induced extravasation of plasma in mouse airways.

PubMed

Erjefält, J S; Andersson, P; Gustafsson, B; Korsgren, M; Sonmark, B; Persson, C G

1998-08-01

Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice. This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin. Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma. Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent. The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation

My child is diagnosed with asthma, now what?: motivating parents to help their children control asthma.

PubMed

Stepney, Cesalie; Kane, Katelyn; Bruzzese, Jean-Marie

2011-10-01

Pediatric asthma is often undiagnosed, and therefore untreated. It negatively impacts children's functioning, including school attendance and performance, as well as quality of life. Schoolwide screening for asthma is becoming increasingly common, making identification of possible asthma particularly relevant for school nurses. Nurses may need to help parents cope with the new diagnosis, and teach them skills to manage the illness. The aim of this article is to present a three-phase model of how parents cope with a newly diagnosed pediatric chronic illness. Using asthma as an example, we describe these phases (Emotional Crisis, Facing Reality, and Reclaiming Life), illustrate how parents progress through the phases, and discuss situations associated with possible regression. Next, we offer strategies framed around a theory of asthma self-management to assist school nurses and other medical providers to motivate parents to develop successful disease management skills.

Adolescent Asthma Self-Management: A Concept Analysis and Operational Definition.

PubMed

Mammen, Jennifer; Rhee, Hyekyun

2012-12-01

BACKGROUND: Adolescents with asthma have a higher risk of morbidity and mortality than other age groups. Asthma self-management has been shown to improve outcomes; however, the concept of asthma self-management is not explicitly defined. METHODS: We use the Norris method of concept clarification to delineate what constitutes the concept of asthma self-management in adolescents. Five databases were searched to identify components of the concept of adolescent asthma self-management, and lists of relevant subconcepts were compiled and categorized. RESULTS: Analysis revealed 4 specific domains of self-management behaviors: (1) symptom prevention; (2) symptom monitoring; (3) acute symptom management; and (4) communication with important others. These domains of self-management were mediated by intrapersonal/cognitive and interpersonal/contextual factors. CONCLUSIONS: Based on the analysis, we offer a research-based operational definition for adolescent asthma self-management and a preliminary model that can serve as a conceptual base for further research.

Geo-Distinctive Comorbidity Networks of Pediatric Asthma.

PubMed

Shin, Eun Kyong; Shaban-Nejad, Arash

2018-01-01

Most pediatric asthma cases occur in complex interdependencies, exhibiting complex manifestation of multiple symptoms. Studying asthma comorbidities can help to better understand the etiology pathway of the disease. Albeit such relations of co-expressed symptoms and their interactions have been highlighted recently, empirical investigation has not been rigorously applied to pediatric asthma cases. In this study, we use computational network modeling and analysis to reveal the links and associations between commonly co-observed diseases/conditions with asthma among children in Memphis, Tennessee. We present a novel method for geo-parsed comorbidity network analysis to show the distinctive patterns of comorbidity networks in urban and suburban areas in Memphis.

[Association between unplanned pregnancy and adolescence onset asthma].

PubMed

Vázquez-Nava, Francisco; Gil-Lara, Bertoldo; Cruz-Torres, Leoncio; Vázquez-Rodríguez, Carlos F; Vázquez-Rodríguez, Eliza M; Felizardo-Ávalos, Jorge; Llanes-Castillo, Arturo; Córdova-Fernández, José A

2013-01-01

The association between asthma and pregnancy has been documented previously. The relationship between unplanned pregnancy and onset asthma in adolescence has not been studied. To determine the association between unplanned pregnancy and adolescence onset asthma. A cross-sectional study was done gathering information about asthma, unplanned pregnancy, family atopy and active or passive smoking in 3,130 adolescents aged 13-19 years. Asthma diagnosis was established through a selfquestionnaire based on the International Study of Asthma and Allergy in Childhood. Odds ratios for asthma were determined using logistic regression model and chi-squared test. Mean age of the participants was 16.37 ± 1.93 years. The prevalence of active smoking was 16.1%, of passive smoking 40% and of family atopy 9.8%. From the pregnant adolescents (785), 59.5% reported had planned not to have a child before pregnancy. Prevalence of wheezing during the year prior to the study was 9.3% and of wheezing during the pregnancy 2%. The prevalence of adolescence onset asthma was 5.4%. The age of initiation of asthma in the adolescence was 14.75 ± 1.60 years. The analysis showed that unplanned pregnancy has a slight risk for the development of asthma during adolescence. (Crude OR=1.03; CI 95% 1.02-1.05; p=0.000). Unplanned pregnancy, family atopy, active smoking and smoking friends are associated with the onset-asthma in the adolescence.

Air pollution and asthma severity in adults

PubMed Central

Rage, Estelle; Siroux, Valérie; Künzli, Nino; Pin, Isabelle; Kauffmann, Francine

2009-01-01

Objectives There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. Methods Asthma severity over the last 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The 4-class severity score integrated clinical events and type of treatment. The 5-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991–1995. The second consisted in spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). Results Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O3-8hr) and the number of days (O3-days) with 8-hour ozone averages above 110 μg.m−3 (for a 36-day increase, equivalent to the inter quartile range, in O3-days, odds ratio (95% confidence interval) 2.22 (1.61–3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO2. Both exposure assessment methods and severity scores resulted in very similar findings. SO2 correlated with severity but reached statistical significance only for the model based assignment of exposure. Conclusions The observed associations between asthma severity and air pollution, in particular O3, support the hypothesis that air pollution at levels far below current standards increases asthma severity. PMID:19017701

Impact of coping and socioeconomic factors on quality of life in adults with asthma.

PubMed

Adams, Robert J; Wilson, David; Smith, Brian J; Ruffin, Richard E

2004-03-01

The socioeconomic variables of income, race and employment status have been shown to influence health-related quality of life (HRQL) scores in persons with asthma. However, little is known about the impact of other psychological factors or perceptions of economic hardship on HRQL in asthma, despite the known influence these have on general activity levels and emotional perceptions. The aim of the present study was to assess the relationships between psychological and socioeconomic factors and HRQL and on subsequent changes to HRQL over 12 months. Consecutive adult patients with moderate or severe asthma attending outpatient clinics, emergency departments or who were inpatients at two teaching hospitals, completed surveys of clinical status, psychological and socioeconomic variables, and HRQL instruments (SF-36 and Modified Marks Asthma Quality of Life Questionnaire [MAQLQ-M]), at baseline and over 12-months follow-up. Of 343 eligible subjects, survey responses were received from 293 at baseline and 232 at 12-months. Mean age was 42 years (SD 18), 67% were female, 42% had moderate, and 58% severe current asthma clinical status according to the National Asthma Education and Prevention Program guidelines criteria. In random-effects multiple regression models, after adjusting for age, gender, education, income and hospital, significant independent variables associated with each of total MAQLQ-M, SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) scores were avoidance coping, perceived recent financial difficulties and clinical asthma status. Additional independent associations were, for total MAQLQ-M, patient concerns about costs delaying them from seeking care (overall model r(2) = 0.69); for PCS, active coping (r(2) = 0.69) and for MCS, positive evaluations/satisfaction with illness (r(2) = 0.54). Psychological factors, particularly coping styles, need to be taken into account when considering HRQL scores as outcome measures in asthma. Interventions to improve the coping capabilities of individuals with moderate-to-severe asthma may be potentially important areas for improvement of asthma-related HRQL.

Parental numeracy and asthma exacerbations in Puerto Rican children.

PubMed

Rosas-Salazar, Christian; Ramratnam, Sima K; Brehm, John M; Han, Yueh-Ying; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Apter, Andrea J; Celedón, Juan C

2013-07-01

Puerto Ricans share a disproportionate burden of childhood asthma in the United States. Little is known about the impact of low parental numeracy (a health literacy skill) on asthma morbidity in Puerto Rican children. Our objective was to examine whether low parental numeracy is associated with increased asthma morbidity in Puerto Rican children. This was a cross-sectional study of 351 children with asthma, aged 6 to 14 years, living in San Juan, Puerto Rico. Parents of study participants completed a modified version of the Asthma Numeracy Questionnaire. Multivariate linear or logistic regression was used to examine the relation between low parental numeracy (defined as no correct answers in the modified Asthma Numeracy Questionnaire) and indicators of asthma morbidity (severe asthma exacerbations, core measures of asthma exacerbations, and lung function measures). All multivariate models were adjusted for age, sex, household income, reported use of inhaled corticosteroids in the previous 6 months, and exposure to secondhand tobacco smoke. Low parental numeracy was associated with increased odds of visits to the ED or urgent care for asthma (adjusted OR [aOR]=1.7, 95% CI=1.03-2.7, P=.04). The association between low parental numeracy and hospitalizations for asthma was significant only among children not using inhaled corticosteroids (aOR=2.8, 95% CI=1.4-5.6, P=.004). There was no association between low parental numeracy and use of systemic steroids or lung function measures. Low parental numeracy is associated with increased asthma morbidity in Puerto Rican children.

Childhood obesity in relation to poor asthma control and exacerbation: a meta-analysis.

PubMed

Ahmadizar, Fariba; Vijverberg, Susanne J H; Arets, Hubertus G M; de Boer, Anthonius; Lang, Jason E; Kattan, Meyer; Palmer, Colin N A; Mukhopadhyay, Somnath; Turner, Steve; Maitland-van der Zee, Anke H

2016-10-01

To estimate the association between obesity and poor asthma control or risk of exacerbations in asthmatic children and adolescents, and to assess whether these associations are different by sex.A meta-analysis was performed on unpublished data from three North-European paediatric asthma cohorts (BREATHE, PACMAN (Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects) and PAGES (Pediatric Asthma Gene Environment Study)) and 11 previously published studies (cross-sectional and longitudinal studies). Outcomes were poor asthma control (based on asthma symptoms) and exacerbations rates (asthma-related visits to the emergency department, asthma-related hospitalisations or use of oral corticosteroids). Overall pooled estimates of the odds ratios were obtained using fixed- or random-effects models.In a meta-analysis of 46 070 asthmatic children and adolescents, obese children (body mass index ≥95th percentile) compared with non-obese peers had a small but significant increased risk of asthma exacerbations (OR 1.17, 95% CI 1.03-1.34; I 2 : 54.7%). However, there was no statistically significant association between obesity and poor asthma control (n=4973, OR 1.23, 95% CI 0.99-1.53; I 2 : 0.0%). After stratification for sex, the differences in odds ratios for girls and boys were similar, yet no longer statistically significant.In asthmatic children, obesity is associated with a minor increased risk of asthma exacerbations but not with poor asthma control. Sex does not appear to modify this risk. Copyright ©ERS 2016.

Coping and social problem solving correlates of asthma control and quality of life.

PubMed

McCormick, Sean P; Nezu, Christine M; Nezu, Arthur M; Sherman, Michael; Davey, Adam; Collins, Bradley N

2014-02-01

In a sample of adults with asthma receiving care and medication in an outpatient pulmonary clinic, this study tested for statistical associations between social problem-solving styles, asthma control, and asthma-related quality of life. These variables were measured cross sectionally as a first step toward more systematic application of social problem-solving frameworks in asthma self-management training. Recruitment occurred during pulmonology clinic service hours. Forty-four adults with physician-confirmed diagnosis of asthma provided data including age, gender, height, weight, race, income, and comorbid conditions. The Asthma Control Questionnaire, the Mini Asthma Quality of Life Questionnaire (Short Form), and peak expiratory force measures offered multiple views of asthma health at the time of the study. Maladaptive coping (impulsive and careless problem-solving styles) based on transactional stress models of health were assessed with the Social Problem-Solving Inventory-Revised: Short Form. Controlling for variance associated with gender, age, and income, individuals reporting higher impulsive-careless scores exhibited significantly lower scores on asthma control (β = 0.70, p = 0.001, confidence interval (CI) [0.37-1.04]) and lower asthma-related quality of life (β = 0.79, p = 0.017, CI [0.15-1.42]). These findings suggest that specific maladaptive problem-solving styles may uniquely contribute to asthma health burdens. Because problem-solving coping strategies are both measureable and teachable, behavioral interventions aimed at facilitating adaptive coping and problem solving could positively affect patient's asthma management and quality of life.

Urinary Peptides As a Novel Source of T Cell Allergen Epitopes

PubMed Central

da Silva Antunes, Ricardo; Pham, John; McMurtrey, Curtis; Hildebrand, William H.; Phillips, Elizabeth; Mallal, Simon; Sidney, John; Busse, Paula; Peters, Bjoern; Schulten, Véronique; Sette, Alessandro

2018-01-01

Mouse allergy in both laboratory workers and in inner-city children is associated with allergic rhinitis and asthma, posing a serious public health concern. Urine is a major source of mouse allergens, as mice spray urine onto their surroundings, where the proteins dry up and become airborne on dust particles. Here, we tested whether oligopeptides that are abundant in mouse urine may contribute to mouse allergic T cell response. Over 1,300 distinct oligopeptides were detected by mass spectrometry analysis of the low molecular weight filtrate fraction of mouse urine (LoMo). Posttranslationally modified peptides were common, accounting for almost half of total peptides. A pool consisting of 225 unique oligopeptides of 13 residues or more in size identified within was tested for its capacity to elicit T cell reactivity in mouse allergic donors. Following 14-day in vitro stimulation of PBMCs, we detected responses in about 95% of donors tested, directed against 116 distinct peptides, predominantly associated with Th2 cytokines (IL-5). Peptides from non-urine related proteins such as epidermal growth factor, collagen, and Beta-globin accounted for the highest response (15.9, 9.1, and 8.1% of the total response, respectively). Peptides derived from major urinary proteins (MUPs), kidney androgen-regulated protein (KAP), and uromodulin were the main T cell targets from kidney or urine related sources. Further ex vivo analysis of enrichment of 4-1BB expressing cells demonstrated that LoMo pool-specific T cell reactivity can be detected directly ex vivo in mouse allergic but not in non-allergic donors. Further cytometric analysis of responding cells revealed a bone fide memory T cell phenotype and confirmed their Th2 polarization. Overall, these data suggest that mouse urine-derived oligopeptides are a novel target for mouse allergy-associated T cell responses, which may contribute to immunopathological mechanisms in mouse allergy. PMID:29755469

Effects of Childhood Asthma on the Development of Obesity among School-aged Children.

PubMed

Chen, Zhanghua; Salam, Muhammad T; Alderete, Tanya L; Habre, Rima; Bastain, Theresa M; Berhane, Kiros; Gilliland, Frank D

2017-05-01

Asthma and obesity often occur together in children. It is unknown whether asthma contributes to the childhood obesity epidemic. We aimed to investigate the effects of asthma and asthma medication use on the development of childhood obesity. The primary analysis was conducted among 2,171 nonobese children who were 5-8 years of age at study enrollment in the Southern California Children's Health Study (CHS) and were followed for up to 10 years. A replication analysis was performed in an independent sample of 2,684 CHS children followed from a mean age of 9.7 to 17.8 years. Height and weight were measured annually to classify children into normal, overweight, and obese categories. Asthma status was ascertained by parent- or self-reported physician-diagnosed asthma. Cox proportional hazards models were fitted to assess associations of asthma history with obesity incidence during follow-up. We found that children with a diagnosis of asthma at cohort entry were at 51% increased risk of developing obesity during childhood and adolescence compared with children without asthma at baseline (hazard ratio, 1.51; 95% confidence interval, 1.08-2.10) after adjusting for confounders. Use of asthma rescue medications at cohort entry reduced the risk of developing obesity (hazard ratio, 0.57; 95% confidence interval, 0.33-0.96). In addition, the significant association between a history of asthma and an increased risk of developing obesity was replicated in an independent CHS sample. Children with asthma may be at higher risk of obesity. Asthma rescue medication use appeared to reduce obesity risk independent of physical activity.

Resource costs for asthma-related care among pediatric patients in managed care.

PubMed

Gendo, Karna; Sullivan, Sean D; Lozano, Paula; Finkelstein, Jonathan A; Fuhlbrigge, Anne; Weiss, Kevin B

2003-09-01

In 1998, the economic burden of asthma in the United States was estimated to be 12.7 billion dollars. Yet few studies have examined the relationship between the total costs of asthma-related care and measures of asthma morbidity. Understanding the relationship between total costs of asthma-related care and morbidity can assist in designing the most cost-effective asthma care strategies to improve patient outcomes and minimize total costs. To investigate correlates of asthma costs for children with mild-to-moderate persistent asthma and, specifically, to characterize how closely the percentage of predicted forced expiratory volume in 1 second (FEV1) and symptom days were correlated with costs of illness. A total of 638 parents and children with mild-to-moderate persistent asthma in 4 managed care delivery systems in 3 different US geographic regions were enrolled. Symptom burden and annual resource utilization were determined from reports of physician visits, hospitalizations, emergency department visits, medication use, and parental missed workdays. Spirometry was conducted on children who were 5 years and older. To characterize the relationship between symptom days and the percentage of predicted FEV1 with costs, we specified a multivariate regression model. The median total annual asthma-related cost for the group was 564 dollars (interquartile range [IQR], 131 dollars-1602 dollars). Indirect costs represented 54.6% of total costs. Medicines accounted for 52.6% of direct costs. The mean percentage of predicted FEV1 was 101.6% (range, 39.3%-183.5%; IQR, 91.6%-111.3%), with 91.4% of patients with a percentage of predicted FEV1 of more than 80%. Based on multivariate modeling, increasing asthma severity, use of peak expiratory flow rate meters, younger age, low-income status and nonwhite race, and longer duration of asthma were significantly associated with increasing cost. Symptom days (P < 0.001) predicted annual costs better than percentage of predicted FEV1 (P < 0.16) in this group of children. For the large number of children with mild-to-moderate persistent asthma and normal or near-normal lung function, symptom days are predictive of health care costs. For these insured children receiving care from 3 large managed care providers, low-income status and nonwhite race were the strongest correlates for increased asthma-related costs.

Childhood asthma and return to school in Sydney, Australia.

PubMed

Lincoln, D; Morgan, G; Sheppeard, V; Jalaludin, B; Corbett, S; Beard, J

2006-09-01

To describe the seasonal pattern of hospital admissions for childhood asthma in Sydney, Australia and investigate the relationship between these admissions and time of return to school. Time-series analysis of daily hospital admissions for childhood asthma in Sydney from 1994 to 2000. We defined the time series of all asthma-related hospital admissions in Sydney between 1994 and 2000 for age groups 1-4 and 5-14 years. We analysed the time series for each age group using a generalized additive model with a log-link function, an offset term and quasi-likelihood estimation. Daily admissions were modelled using penalised regression splines adjusting for long term trends, school terms and holidays, weekday and influenza epidemics. After adjusting for potential confounding, the risk of asthma admission increased to a peak between 2 and 4 weeks after the first day of school in each term and varied between 1.5 and 3 times the risk prior to return to school for both age groups. The largest increase in asthma risk occurring in term one after the long summer holiday. The increase in admission risk began soon after the first day of school of each term for school age children 5-14 years, but not in pre-school age children 1-4 years. Returning to school after term holidays is strongly associated with increased risk of hospital admissions for asthma in children, especially following the long summer holiday. Preventive measures focused on return to school have the potential to substantially decrease admissions for asthma in children.

Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.

PubMed

Huang, Fen; Zhang, Hongkang; Wu, Meng; Yang, Huanghe; Kudo, Makoto; Peters, Christian J; Woodruff, Prescott G; Solberg, Owen D; Donne, Matthew L; Huang, Xiaozhu; Sheppard, Dean; Fahy, John V; Wolters, Paul J; Hogan, Brigid L M; Finkbeiner, Walter E; Li, Min; Jan, Yuh-Nung; Jan, Lily Yeh; Rock, Jason R

2012-10-02

Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in the adult airway surface epithelium and ASM. The epithelial expression is increased in asthmatics, particularly in secretory cells. Based on this and the proposed functions of CaCC, we hypothesized that TMEM16A inhibitors would negatively regulate both epithelial mucin secretion and ASM contraction. We used a high-throughput screen to identify small-molecule blockers of TMEM16A-CaCC channels. We show that inhibition of TMEM16A-CaCC significantly impairs mucus secretion in primary human airway surface epithelial cells. Furthermore, inhibition of TMEM16A-CaCC significantly reduces mouse and human ASM contraction in response to cholinergic agonists. TMEM16A-CaCC blockers, including those identified here, may positively impact multiple causes of asthma symptoms.

Prematurity, atopy, and childhood asthma in Puerto Ricans.

PubMed

Rosas-Salazar, Christian; Ramratnam, Sima K; Brehm, John M; Han, Yueh-Ying; Boutaoui, Nadia; Forno, Erick; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2014-02-01

Puerto Rican children share a disproportionate burden of prematurity and asthma in the United States. Little is known about prematurity and childhood asthma in Puerto Rican subjects. We sought to examine whether prematurity is associated with asthma in Puerto Rican children. We performed a case-control study of 678 children aged 6 to 14 years with (n = 351) and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was defined by parental report for our primary analysis. In a secondary analysis, we only included children whose parents reported prematurity that required admission to the neonatal intensive care unit. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for analysis. All multivariate models were adjusted for age, sex, household income, atopy (≥1 positive IgE level to common allergens), maternal history of asthma, and early-life exposure to environmental tobacco smoke. In a multivariate analysis there was a significant interaction between prematurity and atopy on asthma (P = .006). In an analysis stratified by atopy, prematurity was associated with a nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio, 4.7; 95% CI, 1.5-14.3; P = .007). In contrast, there was no significant association between prematurity and asthma in nonatopic children. Similar results were obtained in our analysis of prematurity requiring admission to the neonatal intensive care unit and asthma. Our results suggest that atopy modifies the estimated effect of prematurity on asthma in Puerto Rican children. Prematurity might explain, in part, the high prevalence of atopic asthma in this ethnic group. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma.

PubMed

Catal, F; Mete, E; Tayman, C; Topal, E; Albayrak, A; Sert, H

2015-01-01

A few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model. Twelve-week-old BALB/c (H-2d/d) female rats (n=18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab (n=6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed. Severity of lung damage was found to be reduced significantly in the asthma induced with OVA+treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score=1, p=0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration. Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria.

PubMed

Agrawal, Anurag; Mabalirajan, Ulaganathan

2016-01-15

Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases. Copyright © 2016 the American Physiological Society.

Rapid non-genomic effects of glucocorticoids on oxidative stress in a guinea pig model of asthma.

PubMed

Long, Fei; Wang, Yan; Qi, Hui-Hui; Zhou, Xin; Jin, Xian-Qiao

2008-03-01

Glucocorticoids (GC) may exert therapeutic effects in asthma by a rapid non-genomic mechanism. The lungs of asthmatic patients are exposed to oxidative stress, which is believed to be critical in the pathogenesis of asthma. The aim of this study was to investigate whether GC exert a rapid non-genomic effect on oxidative stress in asthmatic guinea pigs. The guinea pig asthma model was used to assess inhibitory effects of budesonide (BUD) on oxidative stress. BAL fluid (BALF), trolox equivalent antioxidant capacity and lung manganese superoxide dismutase (MnSOD) activity were measured by spectrophotometry. Superoxide anion production was measured by cytochrome c reduction assay. Oxidative stress occurred within minutes following antigen challenge and BUD reduced the severity of oxidative stress in asthmatic guinea pigs within 15 min. BUD significantly decreased BALF trolox equivalent antioxidant capacity and lung MnSOD activity, as compared with those of vehicle-treated asthmatic guinea pigs (P < 0.05). Additionally, BUD rapidly inhibited in vitro superoxide anion production by BALF cells and bronchi harvested from sensitized animals. These rapid effects were not blocked by the GC receptor antagonist RU486 and/or the protein synthesis inhibitor cycloheximide. BUD reduced oxidative stress in a guinea pig model of asthma by a rapid non-genomic mechanism. These data suggest new mechanisms whereby GC treatments may benefit asthma.

Culture-specific programs for children and adults from minority groups who have asthma.

PubMed

Bailey, Emily J; Cates, Christopher J; Kruske, Sue G; Morris, Peter S; Chang, Anne B; Brown, Ngiare

2009-01-21

People with asthma who come from minority groups have poorer asthma outcomes and more asthma related visits to Emergency Departments (ED). Various programmes are used to educate and empower people with asthma and these have previously been shown to improve certain asthma outcomes. Models of care for chronic diseases in minority groups usually include a focus of the cultural context of the individual and not just the symptoms of the disease. Therefore, questions about whether culturally specific asthma education programmes for people from minority groups are effective at improving asthma outcomes, are feasible and are cost-effective need to be answered. To determine whether culture-specific asthma programmes, in comparison to generic asthma education programmes or usual care, improve asthma related outcomes in children and adults with asthma who belong to minority groups. We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles. The latest search was performed in May 2008. All randomised controlled trials (RCTs) comparing the use of culture-specific asthma education programmes with generic asthma education programmes, or usual care, in adults or children from minority groups who suffer from asthma. Two review authors independently selected, extracted and assessed the data for inclusion. We contacted authors for further information if required. Four studies were eligible for inclusion in the review. A total of 617 patients, aged from 5 to 59 years were included in the meta-analysis of data. Use of a culture-specific programme was superior to generic programmes or usual care, in improving asthma quality of life scores in adults, pooled WMD 0.25 (95% CI 0.09 to 0.41), asthma knowledge scores in children, WMD 3.30 (95% CI 1.07 to 5.53), and in a single study, reducing asthma exacerbation in children (risk ratio for hospitalisations 0.32, 95%CI 0.15, 0.70). Current limited data show that culture-specific programmes for adults and children from minority groups with asthma, are more effective than generic programmes in improving most (quality of life, asthma knowledge, asthma exacerbations, asthma control) but not all asthma outcomes. This evidence is limited by the small number of included studies and the lack of reported outcomes. Further trials are required to answer this question conclusively.

Culture-specific programs for children and adults from minority groups who have asthma.

PubMed

Bailey, Emily J; Cates, Christopher J; Kruske, Sue G; Morris, Peter S; Brown, Ngiare; Chang, Anne B

2009-04-15

People with asthma who come from minority groups have poorer asthma outcomes and more asthma related visits to Emergency Departments (ED). Various programmes are used to educate and empower people with asthma and these have previously been shown to improve certain asthma outcomes. Models of care for chronic diseases in minority groups usually include a focus of the cultural context of the individual and not just the symptoms of the disease. Therefore, questions about whether culturally specific asthma education programmes for people from minority groups are effective at improving asthma outcomes, are feasible and are cost-effective need to be answered. To determine whether culture-specific asthma programmes, in comparison to generic asthma education programmes or usual care, improve asthma related outcomes in children and adults with asthma who belong to minority groups. We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles. The latest search was performed in May 2008. All randomised controlled trials (RCTs) comparing the use of culture-specific asthma education programmes with generic asthma education programmes, or usual care, in adults or children from minority groups who suffer from asthma. Two review authors independently selected, extracted and assessed the data for inclusion. We contacted authors for further information if required. Four studies were eligible for inclusion in the review. A total of 617 patients, aged from 5 to 59 years were included in the meta-analysis of data. Use of a culture-specific programme was superior to generic programmes or usual care, in improving asthma quality of life scores in adults, pooled WMD 0.25 (95% CI 0.09 to 0.41), asthma knowledge scores in children, WMD 3.30 (95% CI 1.07 to 5.53), and in a single study, reducing asthma exacerbation in children (risk ratio for hospitalisations 0.32, 95%CI 0.15, 0.70). Current limited data show that culture-specific programmes for adults and children from minority groups with asthma, are more effective than generic programmes in improving most (quality of life, asthma knowledge, asthma exacerbations, asthma control) but not all asthma outcomes. This evidence is limited by the small number of included studies and the lack of reported outcomes. Further trials are required to answer this question conclusively.

Point source sulphur dioxide peaks and hospital presentations for asthma.

PubMed

Donoghue, A M; Thomas, M

1999-04-01

To examine the effect on hospital presentations for asthma of brief exposures to sulphur dioxide (SO2) (within the range 0-8700 micrograms/m3) emanating from two point sources in a remote rural city of 25,000 people. A time series analysis of SO2 concentrations and hospital presentations for asthma was undertaken at Mount Isa where SO2 is released into the atmosphere by a copper smelter and a lead smelter. The study examined 5 minute block mean SO2 concentrations and daily hospital presentations for asthma, wheeze, or shortness of breath. Generalised linear models and generalised additive models based on a Poisson distribution were applied. There was no evidence of any positive relation between peak SO2 concentrations and hospital presentations or admissions for asthma, wheeze, or shortness of breath. Brief exposures to high concentrations of SO2 emanating from point sources at Mount Isa do not cause sufficiently serious symptoms in asthmatic people to require presentation to hospital.

Volatile Organic Compounds Enhance Allergic Airway Inflammation in an Experimental Mouse Model

PubMed Central

Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

2012-01-01

Background Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. Methods To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Results Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Conclusions Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases. PMID:22802943

Volatile organic compounds enhance allergic airway inflammation in an experimental mouse model.

PubMed

Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C; Lehmann, Irina; Polte, Tobias

2012-01-01

Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases.

Exploring factors influencing asthma control and asthma-specific health-related quality of life among children

PubMed Central

2013-01-01

Background Little is known about factors contributing to children’s asthma control status and health-related quality of life (HRQoL). The study objectives were to assess the relationship between asthma control and asthma-specific HRQoL in asthmatic children, and to examine the extent to which parental health literacy, perceived self-efficacy with patient-physician interaction, and satisfaction with shared decision-making (SDM) contribute to children’s asthma control and asthma-specific HRQoL. Methods This cross-sectional study utilized data collected from a sample of asthmatic children (n = 160) aged 8–17 years and their parents (n = 160) who visited a university medical center. Asthma-specific HRQoL was self-reported by children using the National Institutes of Health’s Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Asthma Impact Scale. Satisfaction with SDM, perceived self-efficacy with patient-physician interaction, parental health literacy, and asthma control were reported by parents using standardized measures. Structural equation modeling (SEM) was performed to test the hypothesized pathways. Results Path analysis revealed that children with better asthma control reported higher asthma-specific HRQoL (β = 0.4, P < 0.001). Parents with higher health literacy and greater perceived self-efficacy with patient-physician interactions were associated with higher satisfaction with SDM (β = 0.38, P < 0.05; β = 0.58, P < 0.001, respectively). Greater satisfaction with SDM was in turn associated with better asthma control (β = −0.26, P < 0.01). Conclusion Children’s asthma control status influenced their asthma-specific HRQoL. However, parental factors such as perceived self-efficacy with patient-physician interaction and satisfaction with shared decision-making indirectly influenced children’s asthma control status and asthma-specific HRQoL. PMID:23432913

Asthma and Risk of Appendicitis in Children: A Population-Based Case-Control Study.

PubMed

Hasassri, M Earth; Jackson, Eric R; Ghawi, Husam; Ryoo, Eell; Wi, Chung-Il; Bartlett, Mark G; Volcheck, Gerald W; Moir, Christopher R; Ryu, Euijung; Juhn, Young J

2017-03-01

To assess whether asthma is associated with risk of appendicitis in children. We used a population-based case-control study design using a comprehensive medical record review and predetermined criteria for appendicitis and asthma. All children (age younger than 18 years of age) who resided in Olmsted County, Minnesota, and developed appendicitis between 2006 and 2012 were matched to controls (1:1) with regard to birthday, gender, registration date, and index date. Asthma status was ascertained using predetermined criteria. Active (current) asthma was defined as the presence of asthma symptoms or asthma-related events (eg, medication use, clinic visits, emergency department, or hospitalization) within 1 year before the index date. Inactive asthma was defined as subjects without these events. A conditional logistic regression model was used. Among the 309 appendicitis cases identified, when stratified according to asthma status, active asthma was associated with significantly increased risk of appendicitis compared with inactive asthma (odds ratio [OR] = 2.48; 95% confidence interval [CI], 1.22-5.03) and to no asthma (OR = 1.88; 95% CI, 1.07-3.27; overall P = .035). When controlling for potential confounders such as gender, age, and smoking status, active asthma was associated with a higher odds of developing appendicitis compared with nonasthmatic patients (adjusted OR = 1.75; 95% CI, 0.99-3.11) whereas inactive asthma was not (overall P = .049). Tobacco smoke exposure within 3 months was associated with an increased risk of appendicitis (adjusted OR = 1.66; 95% CI, 1.02-2.69). Among asthma medications, leukotriene receptor antagonists reduced the risk of appendicitis (OR = 0.18; 95% CI, 0.04-0.74). Active asthma might be an unrecognized risk factor for appendicitis in children whereas a history of inactive asthma does not pose such risk. Further investigation exploring the underlying mechanisms is warranted. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Asthma and risk of appendicitis in children: a population-based case-control study

PubMed Central

Hasassri, M. Earth; Jackson, Eric R.; Ghawi, Husam; Ryoo, Eell; Wi, Chung-Il; Bartlett, Mark G.; Volcheck, Gerald W.; Moir, Christopher R.; Ryu, Euijung; Juhn, Young J.

2017-01-01

Objective To assess whether asthma is associated with risk of appendicitis in children. Methods We used a population-based case-control study design utilizing a comprehensive medical record review and predetermined criteria for appendicitis and asthma. All children (age<18 years) who resided in Olmsted County, Minnesota, and developed appendicitis between 2006 and 2012 were matched to controls (1:1) with regard to birthday, gender, registration date, and index date. Asthma status was ascertained using predetermined criteria. Active (current) asthma was defined as the presence of asthma symptoms or asthma-related events (eg, medication use, clinic visits, emergency department, or hospitalization) within one year prior to the index date. Inactive asthma was defined as subjects without these events. A conditional logistic regression model was used. Results Among the 309 appendicitis cases identified, when stratified by asthma status, active asthma was associated with significantly increased risk of appendicitis when compared to inactive asthma (OR=2.48; 95% CI, 1.22–5.03) and to no asthma (OR=1.88; 95% CI, 1.07–3.27) (overall p-value=0.035). When controlling for potential confounders such as gender, age, and smoking status, active asthma was associated with a higher odds of developing appendicitis compared to non-asthmatics (adjusted OR=1.75, 95% CI 0.99–3.11) whereas inactive asthma was not (overall p-value=0.049). Tobacco smoke exposure within three months was associated with an increased risk of appendicitis (adjusted OR=1.66; 95% CI, 1.02, 2.69). Among asthma medications, leukotriene receptor antagonists reduced the risk of appendicitis (OR=0.18; 95% CI, 0.04–0.74). Conclusions Active asthma may be an unrecognized risk factor for appendicitis in children while a history of inactive asthma does not pose such risk. Further investigation exploring the underlying mechanisms is warranted. PMID:27964827

Prevalence of asthma among adult females and males in the United States: results from the National Health and Nutrition Examination Survey (NHANES), 2001-2004.

PubMed

McHugh, Michelle K; Symanski, Elaine; Pompeii, Lisa A; Delclos, George L

2009-10-01

The prevalence of asthma has increased over the last three decades with females exhibiting a higher prevalence of asthma than males. The objective of this study was to obtain gender-specific estimates of the prevalence of current and ever asthma and describe the relationships between risk factors and asthma by gender in US men and women ages 20 to 85. Data for this study came from two cycles (2001-2002 and 2003-2004) of National Health and Nutrition Examination Survey (NHANES) and included 9,243 eligible adults: 4,589 females and 4,654 males. Multiple logistic regression was used to investigate gender-specific associations between race/ethnicity, body mass index (BMI), sociodemographic characteristics, and smoking habits for current asthma and ever asthma. The prevalence of current asthma was 8.8% for women and 5.8% for men, while the prevalence of ever having been diagnosed with asthma was higher (13.7% and 10.4% for women and men, respectively). Current asthma was less prevalent in Mexican American women (1.9%) and men (0.9%) born in Mexico as compared to Mexican Americans born in the U.S. (8.7% and 5.2% for women and men, respectively) or for any other ethnic group. Approximately 20% of extremely obese women and men had ever been diagnosed with asthma; among this group, 15% reported they had current asthma. Results from multiple logistic regression models indicate that extreme obesity and living in poverty were strongly associated with current and ever asthma for both women and men, as was former smoking and ever asthma for men. As compared to previous NHANES reports, our results indicate that the prevalence of asthma among U.S. adults continues to increase. Further, our findings of marked differences among subgroups of the population suggest asthma-related disparities for impoverished persons and greater prevalence of asthma among obese and extremely obese US adults.

Urban residence, neighborhood poverty, race/ethnicity, and asthma morbidity among children on Medicaid.

PubMed

Keet, Corinne A; Matsui, Elizabeth C; McCormack, Meredith C; Peng, Roger D

2017-09-01

Although poor-urban (inner-city) areas are thought to have high asthma prevalence and morbidity, we recently found that inner cities do not have higher prevalent pediatric asthma. Whether asthma morbidity is higher in inner-city areas across the United States is not known. This study sought to examine relationships between residence in poor and urban areas, race/ethnicity, and asthma morbidity among children with asthma who are enrolled in Medicaid. Children aged 5 to 19 enrolled in Medicaid in 2009 to 2010 were included. Asthma was defined by at least 1 outpatient or emergency department (ED) visit with a primary diagnosis code of asthma over the 2-year period. Urbanization status was defined at the county level and neighborhood poverty at the zip-code level. Among children with asthma, logistic models were created to examine the effects of urbanization, neighborhood poverty, and race/ethnicity on rates of asthma outpatient visits, ED visits, and hospitalizations. This study included 16,860,716 children (1,534,820 with asthma). Among children enrolled in Medicaid, residence in inner-city areas did not confer increased risk of prevalent asthma in either crude or adjusted analyses, but it was associated with significantly more asthma-related ED visits and hospitalizations among those with asthma in crude analyses (risk ratio, 1.48; 95% CI, 1.24-1.36; and 1.97; 95% CI, 1.50-1.72, respectively) and when adjusted for race/ethnicity, age, and sex (adjusted risk ratio, 1.23; 95% CI, 1.08-1.15; and 1.62; 95% CI, 1.26-1.43). Residence in urban or poor areas and non-Hispanic black race/ethnicity were all independently associated with increased risk of asthma-related ED visits and hospitalizations. Residence in poor and urban areas is an important risk factor for asthma morbidity, but not for prevalence, among low-income US children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II).

PubMed

Kogevinas, Manolis; Zock, Jan-Paul; Jarvis, Debbie; Kromhout, Hans; Lillienberg, Linnéa; Plana, Estel; Radon, Katja; Torén, Kjell; Alliksoo, Ada; Benke, Geza; Blanc, Paul D; Dahlman-Hoglund, Anna; D'Errico, Angelo; Héry, Michel; Kennedy, Susan; Kunzli, Nino; Leynaert, Bénédicte; Mirabelli, Maria C; Muniozguren, Nerea; Norbäck, Dan; Olivieri, Mario; Payo, Félix; Villani, Simona; van Sprundel, Marc; Urrutia, Isabel; Wieslander, Gunilla; Sunyer, Jordi; Antó, Josep M

2007-07-28

The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study centre. A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4, 1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2, 1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.

TRIMELLITIC ANHYDRIDE-INDUCED EOSINOPHILIA IN A MURINE MODEL OF OCCUPATIONAL ASTHMA

EPA Science Inventory

TRIMELLITIC ANHYDRIDE-INDUCED EOSINOPHILIA IN A MURINE MODEL OF OCCUPATIONAL ASTHMA. J F Regal, ME Mohrman, E Boykin and D Sailstad. Dept. of Pharmacology, University of Minnesota, Duluth, MN, USA and NHEERL, ORD, US EPA, RTP, NC, USA.
Trimellitic anhydride (TMA) is a small m...

Internal exposure levels of typical POPs and their associations with childhood asthma in Shanghai, China.

PubMed

Meng, Ge; Feng, Yan; Nie, Zhiqing; Wu, Xiaomeng; Wei, Hongying; Wu, Shaowei; Yin, Yong; Wang, Yan

2016-04-01

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are common persistent organic pollutants (POPs) that may be associated with childhood asthma. The concentrations of PBDEs, PCBs and OCPs were analyzed in pooled serum samples from both asthmatic and non-asthmatic children. The differences in the internal exposure levels between the case and control groups were tested (p value <0.0012). The associations between the internal exposure concentrations of the POPs and childhood asthma were estimated based on the odds ratios (ORs) calculated using logistic regression models. There were significant differences in three PBDEs, 26 PCBs and seven OCPs between the two groups, with significantly higher levels in the cases. The multiple logistic regression models demonstrated that the internal exposure concentrations of a number of the POPs (23 PCBs, p,p'-DDE and α-HCH) were positively associated with childhood asthma. Some synergistic effects were observed when the children were co-exposed to the chemicals. BDE-209 was positively associated with asthma aggravation. This study indicates the potential relationships between the internal exposure concentrations of particular POPs and the development of childhood asthma. Copyright © 2015 Elsevier Inc. All rights reserved.

Animal models of asthma: innovative methods of lung research and new pharmacological targets.

PubMed

Braun, Armin; Tschernig, Thomas

2006-06-01

Allergic diseases like bronchial asthma are increasing in societies with western lifestyle. In the last years substantial progress was made in the understanding of the underlying mechanisms and explanations like the hygiene hypothesis were developed. However the exact mechanisms of the physiological and immunological events in the lung leading to bronchial asthma are still not fully understood. Therefore, animal models of asthma have been established and improved to study the complex cellular interactions in vivo. Since mice became the most frequently used animal species the methods for detecting lung physiology, e.g. lung function measurements were adapted to the small size of the murine lung. Laser-dissection and precision cut lung slices have become common techniques to get a view into distinct lung compartments and cells. In addition genomic and proteomic approaches are now used widely. On the other hand a major conclusion of the workshop stated that more than one species is necessary in research and for pharmacological screening in asthma and COPD. The resulting new understanding in the mechanisms of asthma pathogenesis has lead to a rapid identification of novel pharmaceutical targets for treatment of the disease.

Histone deacetylase inhibitors: can we consider potent anti-neoplastic agents for the treatment of asthma?

PubMed

Royce, Simon G; Ververis, Katherine; Karagiannis, Tom C

2012-01-01

Histone deacetylase inhibitors have emerged as a new class of anti-cancer therapeutics due to their potent anti-proliferative and apoptotic effects in malignant cells. Accumulating evidence is indicating that histone deacetylase inhibitors may also have potential clinical utility in non-oncological applications, including asthma. However, the potential of histone deacetylase inhibitors in asthma remains controversial. For example, the mechanisms of action of the broad-spectrum histone deacetylase inhibitor, Trichostatin A, in animal models of allergic airways disease are conflicting. Further, there is evidence suggesting potential problems associated with histone deacetylase 2 inhibition and conventional glucocorticosteroid therapy. Similarly, disparate findings are emerging following modulation of the class III, sirtuin 1 enzyme. Indeed, it is becoming apparent that the mechanism of action may not be related to histone deacetylase inhibition activity per se. Further, there is only limited evidence that these compounds possess anti-inflammatory effects in models of asthma. In this review, we provide an overview of the biology of the metal-dependent and sirtuin deacetylases in the context of asthma. The controversies surrounding the potential use of histone deacetylase inhibitors in asthma are discussed and future directions involving the investigation of more specific analogues are explored.

Uncovering Longitudinal Health Care Behaviors for Millions of Medicaid Enrollees: A Multistate Comparison of Pediatric Asthma Utilization.

PubMed

Hilton, Ross; Zheng, Yuchen; Fitzpatrick, Anne; Serban, Nicoleta

2018-01-01

This study introduces a framework for analyzing and visualizing health care utilization for millions of children, with a focus on pediatric asthma, one of the major chronic respiratory conditions. The data source is the 2005 to 2012 Medicaid Analytic Extract claims for 10 Southeast states. The study population consists of Medicaid-enrolled children with persistent asthma. We translate multiyear, individual-level medical claims into sequences of discrete utilization events, which are modeled using Markov renewal processes and model-based clustering. Network analysis is used to visualize utilization profiles. The method is general, allowing the study of other chronic conditions. The study population consists of 1.5 million children with persistent asthma. All states have profiles with high probability of asthma controller medication, as large as 60.6% to 90.2% of the state study population. The probability of consecutive asthma controller prescriptions ranges between 0.75 and 0.95. All states have utilization profiles with uncontrolled asthma with 4.5% to 22.9% of the state study population. The probability for controller medication is larger than for short-term medication after a physician visit but not after an emergency department (ED) visit or hospitalization. Transitions from ED or hospitalization generally have a lower probability into physician office (between 0.11 and 0.38) than into ED or hospitalization (between 0.20 and 0.59). In most profiles, children who take asthma controller medication do so regularly. Follow-up physician office visits after an ED encounter or hospitalization are observed at a low rate across all states. Finally, all states have a proportion of children who have uncontrolled asthma, meaning they do not take controller medication while they have severe outcomes.

ADCYAP1R1 and asthma in Puerto Rican children.

PubMed

Chen, Wei; Boutaoui, Nadia; Brehm, John M; Han, Yueh-Ying; Schmitz, Cassandra; Cressley, Alex; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Baccarelli, Andrea A; Weeks, Daniel E; Kolls, Jay K; Canino, Glorisa; Celedón, Juan C

2013-03-15

Epigenetic and/or genetic variation in the gene encoding the receptor for adenylate-cyclase activating polypeptide 1 (ADCYAP1R1) has been linked to post-traumatic stress disorder in adults and anxiety in children. Psychosocial stress has been linked to asthma morbidity in Puerto Rican children. To examine whether epigenetic or genetic variation in ADCYAP1R1 is associated with childhood asthma in Puerto Ricans. We conducted a case-control study of 516 children ages 6-14 years living in San Juan, Puerto Rico. We assessed methylation at a CpG site in the promoter of ADCYAP1R1 (cg11218385) using a pyrosequencing assay in DNA from white blood cells. We tested whether cg11218385 methylation (range, 0.4-6.1%) is associated with asthma using logistic regression. We also examined whether exposure to violence (assessed by the Exposure to Violence [ETV] Scale in children 9 yr and older) is associated with cg11218385 methylation (using linear regression) or asthma (using logistic regression). Logistic regression was used to test for association between a single nucleotide polymorphism in ADCYAP1R1 (rs2267735) and asthma under an additive model. All multivariate models were adjusted for age, sex, household income, and principal components. EACH 1% increment in cg11218385 methylation was associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.6; P = 0.03). Among children 9 years and older, exposure to violence was associated with cg11218385 methylation. The C allele of single nucleotide polymorphism rs2267735 was significantly associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.02-1.67; P = 0.03). Epigenetic and genetic variants in ADCYAP1R1 are associated with asthma in Puerto Rican children.

Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children.

PubMed

Blatter, Joshua; Brehm, John M; Sordillo, Joanne; Forno, Erick; Boutaoui, Nadia; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Weiss, Scott T; Litonjua, Augusto A; Canino, Glorisa; Celedón, Juan C

2016-02-01

Little is known about folate and atopy or severe asthma exacerbations. We examined whether folate deficiency is associated with number of positive skin tests to allergens or severe asthma exacerbations in a high-risk population and further assessed whether such association is explained or modified by vitamin D status. Cross-sectional study of 582 children aged 6 to 14 years with (n = 304) and without (n = 278) asthma in San Juan, Puerto Rico. Folate deficiency was defined as plasma folate less than or equal to 20 ng/ml. Our outcomes were the number of positive skin tests to allergens (range, 0-15) in all children and (in children with asthma) one or more severe exacerbations in the previous year. Logistic and negative binomial regression models were used for the multivariate analysis. All multivariate models were adjusted for age, sex, household income, residential proximity to a major road, and (for atopy) case/control status; those for severe exacerbations were also adjusted for use of inhaled corticosteroids and vitamin D insufficiency (a plasma 25[OH]D < 30 ng/ml). In a multivariate analysis, folate deficiency was significantly associated with an increased degree of atopy and 2.2 times increased odds of at least one severe asthma exacerbation (95% confidence interval for odds ratio, 1.1-4.6). Compared with children who had normal levels of both folate and vitamin D, those with both folate deficiency and vitamin D insufficiency had nearly eightfold increased odds of one or more severe asthma exacerbation (95% confidence interval for adjusted odds ratio, 2.7-21.6). Folate deficiency is associated with increased degree of atopy and severe asthma exacerbations in school-aged Puerto Ricans. Vitamin D insufficiency may further increase detrimental effects of folate deficiency on severe asthma exacerbations.

The relationship between combination inhaled corticosteroid and long-acting beta-agonist use and severe asthma exacerbations in a diverse population

PubMed Central

Wells, Karen E.; Peterson, Edward L.; Ahmedani, Brian K.; Severson, Richard K.; Gleason-Comstock, Julie; Williams, L. Keoki

2012-01-01

Background Safety concerns surround the use of long-acting beta agonists (LABA) for the treatment of asthma, even in combination with inhaled corticosteroids (ICS) and particularly in high-risk subgroups. Objective To estimate the effect ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population. Methods Inhaled corticosteroid and ICS/LABA exposure was estimated from pharmacy data for patients with asthma age 12 to 56 years who were members of a large health maintenance organization. Inhaled corticosteroid and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (i.e., use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization). Results Among the 1,828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio [HR]=0.65 vs. HR=0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy. Conclusion Treatment with ICS/LABA fixed combination therapy appeared to perform as well or better than ICS alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups. PMID:22281166

Phthalate esters and childhood asthma: A systematic review and congener-specific meta-analysis.

PubMed

Li, Ming-Chieh; Chen, Chi-Hsien; Guo, Yue Leon

2017-10-01

Exposure to phthalate esters (PAEs) has been associated with childhood asthma, but the congener-specific effects of PAEs on childhood asthma were unclear. We aimed to systematically review and meta-analyze observational studies on the associations between specific effects of PAEs and the risk of childhood asthma. Relevant studies were identified by searching three databases up to October 20, 2016. The reference lists of the retrieved articles were also reviewed. We included observational studies that reported risk estimates with 95% confidence intervals (CIs) for the associations between phthalate exposure and the risk of childhood asthma. Fixed-effects models were generally applied to calculate pooled risk estimates. When heterogeneity was present, random-effects models were applied. A total of nine studies featuring 43 data points were included in our final meta-analyses. Results indicated that the benzyl butyl phthalate (BBzP) exposure had a significant association with the risk of childhood asthma. The Odd Ratios (ORs) were from 1.39 to 1.41 for different combination strategies. Subgroup analyses by different exposure period or samples used showed that prenatal exposure to BBzP had a stronger association with the risk of childhood asthma (OR = 1.38, 95% CI = 1.09-1.75), compared to those with postnatal exposure. Besides, the association was evident when the phthalate exposure was measured from dust samples. The OR for the associations between di-2-ethylhexyl phthalate (DEHP) in dust and childhood asthma was 2.71 (95% CI = 1.39-5.28), and 2.08 (95% CI = 1.10-3.92) for BBzP. Our study suggested a positive association between DEHP and BBzP exposure and childhood asthma. Future studies are warranted to identify the underlying mechanisms of the association. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control of asthma triggers in indoor air with air cleaners: a modeling analysis.

PubMed

Myatt, Theodore A; Minegishi, Taeko; Allen, Joseph G; Macintosh, David L

2008-08-06

Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30-55% lower cat allergen levels, 90-99% lower risk of respiratory infection through the inhalation route of exposure, 90-98% lower environmental tobacco smoke (ETS) levels, and 50-75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.

Control of asthma triggers in indoor air with air cleaners: a modeling analysis

PubMed Central

Myatt, Theodore A; Minegishi, Taeko; Allen, Joseph G; MacIntosh, David L

2008-01-01

Background Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. Methods We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. Results Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. Conclusion These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice. PMID:18684328

History of Asthma From Childhood and Arterial Stiffness in Asymptomatic Young Adults: The Bogalusa Heart Study.

PubMed

Sun, Dianjianyi; Li, Xiang; Heianza, Yoriko; Nisa, Hoirun; Shang, Xiaoyun; Rabito, Felicia; Kelly, Tanika; Harville, Emily; Li, Shengxu; He, Jiang; Bazzano, Lydia; Chen, Wei; Qi, Lu

2018-05-01

Asthma is related to various cardiovascular risk. Whether a history of asthma from childhood contributes to arterial stiffness in adulthood, a noninvasive surrogate for cardiovascular events, is unknown. Prospective analyses were performed among 1746 Bogalusa Heart Study participants aged 20 to 51 years with data on self-report asthma collected since childhood. Aorta-femoral pulse wave velocity (af-PWV, m/s) was repeatedly assessed among adults ≥aged 18 years. Generalized linear mixed models and generalized linear models were fitted for the repeated measurements of af-PWV and its changes between the last and the first measurements, respectively. After a median follow-up of 11.1 years, participants with a history of asthma from childhood had a higher af-PWV (6.78 versus 6.13; P =0.048) and a greater increase in af-PWV (8.99 versus 2.95; P =0.043) than those without asthma, adjusted for age, sex, race, smoking status, heart rate, body mass index, systolic blood pressure, lipids, and glycemia. In addition, we found significant interactions of asthma with body mass index and systolic blood pressure on af-PWV and its changes ( P for interaction <0.01). The associations of asthma with af-PWV and its changes appeared to be stronger among participants who were overweight and obese (body mass index ≥25 kg/m 2 ) or with prehypertension and hypertension (systolic blood pressure ≥120 mm Hg) compared with those with a normal body mass index or systolic blood pressure. Our findings indicate that a history of asthma from childhood is associated with higher af-PWV and greater increases in af-PWV, and such associations are stronger among young adults who are overweight or with elevated blood pressure. © 2018 American Heart Association, Inc.

Costs Attributable to Overweight and Obesity in Working Asthma Patients in the United States

PubMed Central

Chang, Chongwon; Lee, Seung-Mi; Choi, Byoung-Whui; Song, Jong-hwa; Song, Hee; Jung, Sujin; Bai, Yoon Kyeong; Park, Haedong; Jeung, Seungwon

2017-01-01

Purpose To estimate annual health care and productivity loss costs attributable to overweight or obesity in working asthmatic patients. Materials and Methods This study was conducted using the 2003–2013 Medical Expenditure Panel Survey (MEPS) in the United States. Patients aged 18 to 64 years with asthma were identified via self-reported diagnosis, a Clinical Classification Code of 128, or a ICD-9-CM code of 493.xx. All-cause health care costs were estimated using a generalized linear model with a log function and a gamma distribution. Productivity loss costs were estimated in relation to hourly wages and missed work days, and a two-part model was used to adjust for patients with zero costs. To estimate the costs attributable to overweight or obesity in asthma patients, costs were estimated by the recycled prediction method. Results Among 11670 working patients with a diagnosis of asthma, 4428 (35.2%) were obese and 3761 (33.0%) were overweight. The health care costs attributable to obesity and overweight in working asthma patients were estimated to be $878 [95% confidence interval (CI): $861–$895] and $257 (95% CI: $251–$262) per person per year, respectively, from 2003 to 2013. The productivity loss costs attributable to obesity and overweight among working asthma patients were $256 (95% CI: $253–$260) and $26 (95% CI: $26–$27) per person per year, respectively. Conclusion Health care and productivity loss costs attributable to overweight and obesity in asthma patients are substantial. This study's results highlight the importance of effective public health and educational initiatives targeted at reducing overweight and obesity among patients with asthma, which may help lower the economic burden of asthma. PMID:27873513

Costs Attributable to Overweight and Obesity in Working Asthma Patients in the United States.

PubMed

Chang, Chongwon; Lee, Seung Mi; Choi, Byoung Whui; Song, Jong Hwa; Song, Hee; Jung, Sujin; Bai, Yoon Kyeong; Park, Haedong; Jeung, Seungwon; Suh, Dong Churl

2017-01-01

To estimate annual health care and productivity loss costs attributable to overweight or obesity in working asthmatic patients. This study was conducted using the 2003-2013 Medical Expenditure Panel Survey (MEPS) in the United States. Patients aged 18 to 64 years with asthma were identified via self-reported diagnosis, a Clinical Classification Code of 128, or a ICD-9-CM code of 493.xx. All-cause health care costs were estimated using a generalized linear model with a log function and a gamma distribution. Productivity loss costs were estimated in relation to hourly wages and missed work days, and a two-part model was used to adjust for patients with zero costs. To estimate the costs attributable to overweight or obesity in asthma patients, costs were estimated by the recycled prediction method. Among 11670 working patients with a diagnosis of asthma, 4428 (35.2%) were obese and 3761 (33.0%) were overweight. The health care costs attributable to obesity and overweight in working asthma patients were estimated to be $878 [95% confidence interval (CI): $861-$895] and $257 (95% CI: $251-$262) per person per year, respectively, from 2003 to 2013. The productivity loss costs attributable to obesity and overweight among working asthma patients were $256 (95% CI: $253-$260) and $26 (95% CI: $26-$27) per person per year, respectively. Health care and productivity loss costs attributable to overweight and obesity in asthma patients are substantial. This study's results highlight the importance of effective public health and educational initiatives targeted at reducing overweight and obesity among patients with asthma, which may help lower the economic burden of asthma.

Childhood asthma: considerations for primary care practice and chronic disease management in the village of care.

PubMed

Rosenthal, Michael P

2012-06-01

Childhood asthma is at historically high levels, with significant morbidity and mortality. Despite more than two decades of improved understanding of childhood asthma care and the evolution of beneficial medications, widespread control remains poor, leading to suboptimal patient outcomes and quality of life. This lack of control results in excessive emergency department use, hospitalizations, and inappropriate and/or unnecessary costs to the health care system. Advanced practice models that incorporate community-based approaches and services for childhood asthma are needed. Innovative, community-included methods of care to address the burden of childhood asthma may provide examples for care of other chronic diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of Polyamines in Asthma Pathophysiology

PubMed Central

2018-01-01

Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and their interactions have been associated with different pathological conditions including asthma. Elevated levels of polyamines have been reported in the circulation of asthmatic patients as well as in the lungs of a murine model of asthma. In various studies, polyamines were found to potentiate the pathogenic potential of inflammatory cells, such as mast cells and granulocytes (eosinophils and neutrophils), by either inducing the release of their pro-inflammatory mediators or prolonging their life span. Additionally, polyamines were crucial in the differentiation and alternative activation of macrophages, which play an important role in asthma pathology. Importantly, polyamines cause airway smooth muscle contraction and thus airway hyper-responsiveness, which is the key feature in asthma pathophysiology. High levels of polyamines in asthma and their active cellular and macromolecular interactions indicate the importance of the polyamine pathway in asthma pathogenesis; therefore, modulation of polyamine levels could be a suitable approach in acute and severe asthma management. This review summarizes the possible roles of polyamines in different pathophysiological features of asthma. PMID:29316647

Cleaning and asthma: A systematic review and approach for effective safety assessment.

PubMed

Vincent, Melissa J; Parker, Ann; Maier, Andrew

2017-11-01

Research indicates a correlative relationship between asthma and use of consumer cleaning products. We conduct a systematic review of epidemiological literature on persons who use or are exposed to cleaning products, both in occupational and domestic settings, and risk of asthma or asthma-like symptoms to improve understanding of the causal relationship between exposure and asthma. A scoring method for assessing study reliability is presented. Although research indicates an association between asthma and the use of cleaning products, no study robustly investigates exposure to cleaning products or ingredients along with asthma risk. This limits determination of causal relationships between asthma and specific products or ingredients in chemical safety assessment. These limitations, and a lack of robust animal models for toxicological assessment of asthma, create the need for a weight-of-evidence (WoE) approach to examine an ingredient or product's asthmatic potential. This proposed WoE method organizes diverse lines of data (i.e., asthma, sensitization, and irritation information) through a systematic, hierarchical framework that provides qualitatively categorized conclusions using hazard bands to predict a specific product or ingredient's potential for asthma induction. This work provides a method for prioritizing chemicals as a first step for quantitative and scenario-specific safety assessments based on their potential for inducing asthmatic effects. Acetic acid is used as a case study to test this framework. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

B-Glucan exacerbates allergic asthma independent of fungal ...

EPA Pesticide Factsheets

BackgroundAllergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity.ObjectiveWe sought to determine the mechanism by which fungi affect asthma development and severity.MethodsWe integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity.ResultsWe report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with β-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc−/− mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity.ConclusionOur data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma. To describe th

Asthma and obesity among 3 year old urban children: The role of sex and the home environment

PubMed Central

Suglia, Shakira Franco; Chambers, Earle; Rosario, Andres; Duarte, Cristiane S.

2011-01-01

Objective To examine whether the relationship between obesity and asthma in young girls and boys can be explained by social and physical characteristics of the home environment. Study design We examined the relationship between asthma and obesity among children in the Fragile Families and Child Wellbeing study (N=1815). Asthma was determined through maternal report of asthma diagnosis by a doctor (active in past 12 months). Weight and height of child was measured during an in-home visit. Data on home social (maternal depression, intimate partner violence) and physical environmental factors (housing quality, tobacco exposure) were collected by questionnaire. Results Ten percent of children had active asthma, 19% were overweight and 17% were obese. In fully adjusted models, obese children had twice the odds of having asthma (OR 2.3 95%CI 1.5, 3.3) compared with children of normal body weight. In stratified analyses overweight boys, but not overweight girls, had an increased of odds of asthma. Obese boys and girls had an increased odds of asthma compared with boys and girls of normal body weight. Conclusion The relationship between asthma and obesity is present in boys and girls as young as 3 years of age, a relationship between being overweight and asthma is only present among boys. This relationship is not attributable to shared social and environmental factors of the children’s home. PMID:21392787

Integrating asthma hazard characterization methods for consumer products.

PubMed

Maier, A; Vincent, M J; Gadagbui, B; Patterson, J; Beckett, W; Dalton, P; Kimber, I; Selgrade, M J K

2014-10-01

Despite extensive study, definitive conclusions regarding the relationship between asthma and consumer products remain elusive. Uncertainties reflect the multi-faceted nature of asthma (i.e., contributions of immunologic and non-immunologic mechanisms). Many substances used in consumer products are associated with occupational asthma or asthma-like syndromes. However, risk assessment methods do not adequately predict the potential for consumer product exposures to trigger asthma and related syndromes under lower-level end-user conditions. A decision tree system is required to characterize asthma and respiratory-related hazards associated with consumer products. A system can be built to incorporate the best features of existing guidance, frameworks, and models using a weight-of-evidence (WoE) approach. With this goal in mind, we have evaluated chemical hazard characterization methods for asthma and asthma-like responses. Despite the wealth of information available, current hazard characterization methods do not definitively identify whether a particular ingredient will cause or exacerbate asthma, asthma-like responses, or sensitization of the respiratory tract at lower levels associated with consumer product use. Effective use of hierarchical lines of evidence relies on consideration of the relevance and potency of assays, organization of assays by mode of action, and better assay validation. It is anticipated that the analysis of existing methods will support the development of a refined WoE approach. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Epigenetics in allergic diseases and asthma].

PubMed

Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

2016-01-01

Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Parental coping, depressive symptoms, and children's asthma control and school attendance in low-income, racially, and ethnically diverse urban families.

PubMed

Rodríguez, Erin M; Kumar, Harsha; Alba-Suarez, Juliana; Sánchez-Johnsen, Lisa

2017-10-01

Low-income urban children of color are at elevated risk for poor asthma control. This cross-sectional study examined associations among parents' coping (primary control, secondary control, and disengagement), parental depressive symptoms, and children's asthma outcomes (asthma control and school attendance) in a predominantly low-income, racially/ethnically diverse sample of families. Parents (N = 78; 90% female) of children (33% female; 46% Black; 38% Latino) aged 5-17 years (M = 9.5 years) reported on their own coping and depressive symptoms, their child's asthma control, and full and partial days of school missed due to asthma. Parents' secondary control coping (i.e., coping efforts to accommodate/adapt to asthma-related stressors) was negatively correlated, and disengagement coping (i.e. coping efforts to avoid/detach from stressors) was positively correlated, with their depressive symptoms. Secondary control coping was also correlated with fewer partial days of school missed. Primary control coping (i.e., coping efforts to change stressors) was not associated with depressive symptoms or asthma outcomes. Parents' depressive symptoms were also positively correlated with poorer asthma control and partial days of school missed. Regression models showed direct and indirect effects of secondary control and disengagement coping on asthma outcomes via depressive symptoms, after controlling for demographic factors. Parents' secondary control and disengagement coping are related to children's asthma outcomes. Secondary control coping may support parents' mental health and children's asthma control in low-income urban families.

Interaction effect of psychological distress and asthma control on productivity loss?

PubMed

Moullec, Grégory; FitzGerald, J Mark; Rousseau, Roxanne; Chen, Wenjia; Sadatsafavi, Mohsen

2015-06-01

Little is known about the potential synergistic effect of comorbid psychological distress (PD) and uncontrolled asthma (UA) on productivity loss. We estimated the productivity loss associated with the combination of these two potentially preventable conditions in employed adults with asthma. A population-based random sample of 300 adults with asthma in British Columbia, Canada, was prospectively recruited between Dec 2010 and Aug 2012. PD and productivity loss due to absenteeism and presenteeism was measured using validated instruments, and asthma control was ascertained using 2010 Global Initiative for Asthma management strategy. We used two-part regression models to study the contribution of UA and PD to productivity loss. Compared with reference group (controlled asthma (CA)+noPD), those with UA+noPD had CAD$286 (95%CI $276-297) weekly productivity loss, and those with CA+PD had CAD$465 ($445-485). Those with UA+PD had CAD$449 (437-462) in productivity loss. There was no significant interaction effect of PD with asthma control levels on productivity loss (p=0.22). In patients without PD, uncontrolled asthma was associated with a higher productivity loss than controlled asthma, but this was not the case in patients with PD. This finding can be explained by the fact that the contribution of PD to productivity loss is so large that there is no room for synergy with asthma control. Future studies should assess the impact of interventions that modify PD in patients with asthma. Copyright ©ERS 2015.

Alterations of the arginine metabolome in asthma.

PubMed

Lara, Abigail; Khatri, Sumita B; Wang, Zeneng; Comhair, Suzy A A; Xu, Weiling; Dweik, Raed A; Bodine, Melanie; Levison, Bruce S; Hammel, Jeffrey; Bleecker, Eugene; Busse, William; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar; Moore, Wendy; Peters, Stephen P; Teague, W Gerald; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2008-10-01

As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated. Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma. Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.

Parental Numeracy and Asthma Exacerbations in Puerto Rican Children

PubMed Central

Rosas-Salazar, Christian; Ramratnam, Sima K.; Brehm, John M.; Han, Yueh-Ying; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Apter, Andrea J.

2013-01-01

Background: Puerto Ricans share a disproportionate burden of childhood asthma in the United States. Little is known about the impact of low parental numeracy (a health literacy skill) on asthma morbidity in Puerto Rican children. Our objective was to examine whether low parental numeracy is associated with increased asthma morbidity in Puerto Rican children. Methods: This was a cross-sectional study of 351 children with asthma, aged 6 to 14 years, living in San Juan, Puerto Rico. Parents of study participants completed a modified version of the Asthma Numeracy Questionnaire. Multivariate linear or logistic regression was used to examine the relation between low parental numeracy (defined as no correct answers in the modified Asthma Numeracy Questionnaire) and indicators of asthma morbidity (severe asthma exacerbations, core measures of asthma exacerbations, and lung function measures). All multivariate models were adjusted for age, sex, household income, reported use of inhaled corticosteroids in the previous 6 months, and exposure to secondhand tobacco smoke. Results: Low parental numeracy was associated with increased odds of visits to the ED or urgent care for asthma (adjusted OR [aOR] = 1.7, 95% CI = 1.03-2.7, P = .04). The association between low parental numeracy and hospitalizations for asthma was significant only among children not using inhaled corticosteroids (aOR = 2.8, 95% CI = 1.4-5.6, P = .004). There was no association between low parental numeracy and use of systemic steroids or lung function measures. Conclusions: Low parental numeracy is associated with increased asthma morbidity in Puerto Rican children. PMID:23493983

Characterization of Rhinitis According to the Asthma Status in Adults Using an Unsupervised Approach in the EGEA Study.

PubMed

Burte, Emilie; Bousquet, Jean; Varraso, Raphaëlle; Gormand, Frédéric; Just, Jocelyne; Matran, Régis; Pin, Isabelle; Siroux, Valérie; Jacquemin, Bénédicte; Nadif, Rachel

2015-01-01

The classification of rhinitis in adults is missing in epidemiological studies. To identify phenotypes of adult rhinitis using an unsupervised approach (data-driven) compared with a classical hypothesis-driven approach. 983 adults of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis, and sensitivities to different triggers (dust, animals, hay/flowers, cold air…) were used. Allergic sensitization was defined by at least one positive skin prick test to 12 aeroallergens. Mixture model was used to cluster participants, independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n = 401). Three clusters were identified in both groups: 1) Cluster A (55% in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by nasal symptoms all over the year, sinusitis and a low prevalence of positive skin prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly characterized by a peak of nasal symptoms during spring, a high prevalence of positive skin prick tests and a high report of hay fever, allergic rhinitis and conjunctivitis. The highest rate of polysensitization (80%) was found in participants with comorbid asthma and allergic rhinitis. This cluster analysis highlighted three clusters of rhinitis with similar characteristics than those known by clinicians but differing according to allergic sensitization, and this whatever the asthma status. These clusters could be easily rebuilt using a small number of variables.

Air pollution and ED visits for asthma in Australian children: a case-crossover analysis.

PubMed

Jalaludin, Bin; Khalaj, Behnoosh; Sheppeard, Vicky; Morgan, Geoff

2008-08-01

We aimed to determine the effects of ambient air pollutants on emergency department (ED) visits for asthma in children. We obtained routinely collected ED visit data for asthma (ICD9 493) and air pollution (PM(10), PM(2.5), O(3), NO(2), CO and SO(2)) and meteorological data for metropolitan Sydney for 1997-2001. We used the time stratified case-crossover design and conditional logistic regression to model the association between air pollutants and ED visits for four age-groups (1-4, 5-9, 10-14 and 1-14 years). Estimated relative risks for asthma ED visits were calculated for an exposure corresponding to the inter-quartile range in pollutant level. We included same day average temperature, same day relative humidity, daily temperature range, school holidays and public holidays in all models. Associations between ambient air pollutants and ED visits for asthma in children were most consistent for all six air pollutants in the 1-4 years age-group, for particulates and CO in the 5-9 years age-group and for CO in the 10-14 years age-group. The greatest effects were most consistently observed for lag 0 and effects were greater in the warm months for particulates, O(3) and NO(2). In two pollutant models, effect sizes were generally smaller compared to those derived from single pollutant models. We observed the effects of ambient air pollutants on ED attendances for asthma in a city where the ambient concentrations of air pollutants are relatively low.

Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model

PubMed Central

Koloze, Mary; Lennon, Donald P.; Zuchowski, Brandon; Yang, Sung Eun; Caplan, Arnold I.

2010-01-01

Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma. PMID:20817776

Effectiveness of a School- and Community-based Academic Asthma Health Education Program on Use of Effective Asthma Self-care Behaviors in Older School-age Students

PubMed Central

Kintner, Eileen K.; Cook, Gwendolyn; Marti, C. Nathan; Allen, April; Stoddard, Debbie; Harmon, Phyllis; Gomes, Melissa; Meeder, Linda; Van Egeren, Laurie A.

2014-01-01

Purpose The purpose was to evaluate the effectiveness of SHARP, an academic asthma health education and counseling program, on fostering use of effective asthma self-care behaviors. Design and Methods This was a phase III, two-group, cluster randomized, single-blinded, longitudinal design guided the study. Caregivers of 205 fourth- and fifth-grade students completed the asthma health behaviors survey at pre-intervention and 1, 12, and 24 months post-intervention. Analysis involved multilevel modeling. Results All students demonstrated improvement in episode management, risk-reduction/prevention, and health promotion behaviors; SHARP students demonstrated increased improvement in episode management and risk-reduction/prevention behaviors. Practice Implications Working with schoolteachers, nurses can improve use of effective asthma self-care behaviors. PMID:25443867

Eastern Carolina Asthma Prevention Program (ECAPP): An Environmental Intervention Study Among Rural and Underserved Children with Asthma in Eastern North Carolina

PubMed Central

Kearney, Gregory D; Johnson, Lisa C; Xu, Xiaohui; Balanay, Jo Anne G; Lamm, Kevin M; Allen, Daniel L

2014-01-01

OBJECTIVE Asthma is the most common chronic childhood condition affecting 6.3 million (US) children aged less than 18 years. Home-based, multi-component, environmental intervention studies among children with asthma have demonstrated to be effective in reducing asthma symptoms. In this study, a local hospital and university developed an environmental intervention research pilot project, Eastern Carolina Asthma Prevention Program (ECAPP), to evaluate self-reported asthma symptoms, breathing measurements, and number of asthma-related emergency department (ED) visits among low-income, minority children with asthma living in rural, eastern North Carolina. Our goal was to develop a conceptual model and demonstrate any asthma respiratory improvements in children associated with our home-based, environmental intervention. METHODS This project used a single cohort, intervention design approach to compare self-reported asthma-related symptoms, breathing tests, and ED visits over a 6 month period between children with asthma in an intervention study group (n = 12) and children with asthma in a control study group (n = 7). The intervention study group received intense asthma education, three home visits, 2 week follow-up telephone calls, and environmental intervention products for reducing asthma triggers in the home. The control group received education at baseline and 2 week calls, but no intervention products. RESULTS At the end of the study period, significant improvements were observed in the intervention group compared with the control group. Overall, the intervention group experienced a 58% (46 ± SD 26.9) reduction in self-reported asthma symptoms; 76% (34 ± SD 29.7) decrease in rescue medicine; 12% (145 ± SD 11.3) increase in controller medicine; 37% decrease in mean exhaled nitric oxide levels and 33% fewer ED asthma-related visits. CONCLUSION As demonstrated, a combination of efforts appeared effective for improving asthma respiratory symptoms among children in the intervention group. ECAPP is a low cost pilot project that could readily be adapted and expanded into other communities throughout eastern North Carolina. Future efforts could include enhanced partnerships between environmental health professionals at local health departments and pediatric asthma programs at hospitals to carry out ECAPP. PMID:25057240

Depression and Risk of Incident Asthma in Adults. The CARDIA Study

PubMed Central

Schreiner, Pamela J.; Sood, Akshay; Jacobs, David R.

2014-01-01

Rationale: Asthma is associated with depression, but the temporality of the association has not been established. Objectives: To examine the association between prevalent elevated depressive symptoms and incident asthma, and between prevalent asthma and incident elevated depressive symptoms in a cohort of young and middle-aged adults. Methods: We examined the longitudinal association between asthma and depressive symptoms bidirectionally in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. First, 3,614 participants, free of asthma, were classified by elevated depressive symptoms at the CARDIA Year-5 exam (n = 856 elevated vs. 2,758 not elevated; ages 23–35 yr) and followed for 20 years to incident asthma. Then, 3,016 participants, free of elevated depressive symptoms, were classified by self-reported current asthma status (n = 188 prevalent vs. 2,828 not prevalent) at the CARDIA Year-5 exam and followed for 20 years until onset of elevated depressive symptoms. Measurements and Main Results: The relative hazard of incident asthma among those with elevated depressive symptoms was 1.26 (95% confidence interval [CI] = 1.02–1.56) after adjustment for covariates. When depressive status was modeled as the total number of reports of elevated depressive symptoms before the onset of asthma, the adjusted hazard ratio was 1.15 (95% CI = 1.02–1.29). The hazard of incident elevated depressive symptoms for those with asthma was no different than the hazard in those without asthma (adjusted hazard ratio = 0.92; 95% CI = 0.70–1.20). Conclusions: This longitudinal observational study points to depression as a marker of risk for incident adult-onset asthma. On the other hand, prevalent asthma is not associated with incident adult-onset depression. PMID:24456492

Prematurity, atopy, and childhood asthma in Puerto Ricans

PubMed Central

Rosas-Salazar, Christian; Ramratnam, Sima K.; Brehm, John M.; Han, Yueh-Ying; Boutaoui, Nadia; Forno, Erick; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C.

2013-01-01

Background Puerto Rican children share a disproportionate burden of prematurity and asthma in the United States. Little is known about prematurity and childhood asthma in Puerto Rican subjects. Objective We sought to examine whether prematurity is associated with asthma in Puerto Rican children. Methods We performed a case-control study of 678 children aged 6 to 14 years with (n = 351) and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was defined by parental report for our primary analysis. In a secondary analysis, we only included children whose parents reported prematurity that required admission to the neonatal intensive care unit. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for analysis. All multivariate models were adjusted for age, sex, household income, atopy (≥1 positive IgE level to common allergens), maternal history of asthma, and early-life exposure to environmental tobacco smoke. Results In a multivariate analysis there was a significant interaction between prematurity and atopy on asthma (P = .006). In an analysis stratified by atopy, prematurity was associated with a nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio, 4.7; 95% CI, 1.5–14.3; P = .007). In contrast, there was no significant association between prematurity and asthma in nonatopic children. Similar results were obtained in our analysis of prematurity requiring admission to the neonatal intensive care unit and asthma. Conclusions Our results suggest that atopy modifies the estimated effect of prematurity on asthma in Puerto Rican children. Prematurity might explain, in part, the high prevalence of atopic asthma in this ethnic group. PMID:24139607

Change in the manifestations of asthma and asthma-related traits in childhood: a latent transition analysis.

PubMed

Garden, Frances L; Simpson, Judy M; Mellis, Craig M; Marks, Guy B

2016-02-01

It is known that asthma is a heterogeneous entity whose manifestations vary with age. Our objective was to examine changes in the manifestation of asthma and asthma-related traits in childhood by defining empirically derived childhood asthma phenotypes and examining their transitions over time.To define the phenotypes we used data on respiratory symptoms, healthcare utilisation, medications, spirometry, airway hyperresponsiveness (AHR), exhaled nitric oxide concentration and atopy from a birth cohort recruited on the basis of having a first-degree relative with asthma. Data were acquired at ages 1.5-11.5 years and analysed using latent transition analysis.In a study population of 370 participants, we classified subjects into four phenotypes: 1) nonatopic, few symptoms (prevalence range from 1.5 to 5 years: 52-60%), 2) atopic, few symptoms (3-21%), 3) nonatopic, asthma and rhinitis symptoms (13-35%), and 4) atopic, asthma and rhinitis symptoms (2-14%) in early childhood; and 1) nonatopic, no respiratory disease (prevalence range from 8 to 11.5 years: 41-46%), 2) atopic, no respiratory disease (23-33%), 3) nonatopic, asthma symptoms, no AHR or airway inflammation (8-12%) and 4) atopic asthma (19%) in mid-childhood. Transitioning between phenotypes was common in early childhood, but less common in later childhood.This analysis represents the first attempt to incorporate longitudinal patterns of several manifestations of asthma into a single model to simultaneously define phenotypes and examine their transitions over time. It provides quantitative support for the view that asthma is a heterogeneous entity, and that some children with wheeze and other respiratory symptoms in early life progress to asthma in mid-childhood, while others become asymptomatic. Copyright ©ERS 2016.

Asthma Control and Sputum Eosinophils: A Longitudinal Study in Daily Practice.

PubMed

Demarche, Sophie F; Schleich, Florence N; Paulus, Virginie A; Henket, Monique A; Van Hees, Thierry J; Louis, Renaud E

Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice. To investigate the relationship between asthma control and sputum eosinophils in clinical practice. A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values. A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P < .001). In patients with intermittent/persistently eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P < .001) or 3.4-fold (AUC, 0.65; P = .003) for a significant improvement in asthma control and a minimal important increase of 3.5% (AUC, 0.67; P = .004) or 1.8-fold (AUC, 0.63; P = .02) for a significant worsening in asthma control. The association between asthma control and sputum eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort. At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Determinants of longitudinal health-related quality-of-life change in children with asthma from low-income families: a report from the PROMIS® Pediatric Asthma Study.

PubMed

Li, Z; Leite, W L; Thompson, L A; Gross, H E; Shenkman, E A; Reeve, B B; DeWalt, D A; Huang, I-C

2017-03-01

How the longitudinal asthma control status and other socio-demographic factors influence the changes of health-related quality of life (HRQOL) among asthmatic children, especially from low-income families, has not been fully investigated. This study aimed to describe the trajectories of asthma-specific HRQOL over 15 months and examine the effect of asthma control status on HRQOL by taking socio-demographic factors into consideration. A total of 229 dyads of asthmatic children and their parents enroled in public insurance programs were recruited for assessing asthma control status and HRQOL over four time points of assessment. Asthma control status was measured using the Asthma Control and Communication Instrument, and asthma-specific HRQOL was assessed using the Patient-Reported Outcomes Measurement Information System's Pediatric Asthma Impact Scale. Latent growth models (LGMs) were applied to examine the trajectory of HRQOL and the factors contributing to the changes of HRQOL. Unconditional LGM revealed that HRQOL was improved over time. Conditional LGM suggested that accounting for asthma control and participants' socio-demographic factors, the variation in the initial level of HRQOL was significant, yet the rate of change was not. Conditional LGM also revealed that poorly controlled asthma status was associated with poor HRQOL at each time point (P's < 0.05). Lower parental education was associated with lower baseline HRQOL (P < 0.05). Hispanic children had a larger increase in HRQOL over time (P < 0.01) than non-Hispanic White children. Vulnerable socio-demographic characteristics and poorly controlled asthma status affect HRQOL in children. This finding encourages interventions to improve asthma control status and HRQOL in minority children. © 2016 John Wiley & Sons Ltd.

Genetic variation within the histamine pathway among patients with asthma

PubMed Central

Raje, Nikita; Vyhlidal, Carrie A.; Dai, Hongying; Jones, Bridgette L.

2015-01-01

Objective Histamine is an important mediator in the pathophysiology of asthma. We have previously reported that HRH1 is differentially expressed among those with asthma compared to those without asthma. Single histamine related genes have also been associated with asthma. We aimed to evaluate known single nucleotide polymorphisms (SNPs) in genes along the histamine biotransformation and response pathway and determine their association with asthma and HRH1 mRNA expression. Methods We enrolled children and adults (n=93) with/without asthma who met inclusion/exclusion criteria. Genotyping was performed for 9 known SNPs in the HDC, HRH1, HRH4, HNMT, and ABP1 genes. HRH1 mRNA expression was determined on RNA from buccal tissue. General linear model, Fisher's exact test, and Chi-square test were used to determine differences in allele, genotype, and haplotype frequency between subjects with and without asthma and differential HRH1 mRNA expression relative to genotype. Statistical significance was determined by p<0.05. Results No difference was observed in genotype/allele frequency for the 9 SNPs between subjects with and without asthma. The HNMT-1639C/ −464C/ 314C/ 3’UTRA haplotype was more frequently observed in those without asthma than those with asthma (p=0.03). We also observed genetic differences relative to race and gender. HNMT 314 genotype CT was more frequent in males with asthma compared to those without asthma (p=0.04). Conclusions Histamine pathway haplotype was associated with a diagnosis of asthma in our cohort but allele and genotype were not. Subgroup evaluations may also be important. Further studies are needed to determine the potential biological/clinical significance of our findings. PMID:25295384