Using your Metered Dose Inhaler
Using your Spacer
Using Your Accuhaler/Advair Diskus
Using your Turbuhaler
Using your Autohaler
Related:
Proper techniques for the administration of inhaled medications to treat asthma - AAAAI - Ask the Expert, 2011.
Videos: How to use your asthma inhalers
The videos below are from the Asthma Foundation NSW, Australia. You can follow them on Twitter at @AsthmaNSW and YouTube.
Using your Metered Dose Inhaler
Using your Spacer
Using Your Accuhaler/Advair Diskus
Using your Turbuhaler
Using your Autohaler
Using your Metered Dose Inhaler
Using your Spacer
Using Your Accuhaler/Advair Diskus
Using your Turbuhaler
Using your Autohaler
Cyclosporine effect in atopic dermatitis may be mediated by increase of Treg cells
Atopic dermatitis (AD) is a T cell dependent chronic relapsing inflammatory skin disorder successfully treated with cyclosporine A (CsA). Even low-dose CsA therapy is successful in severely affected AD patients.
Cyclosporine and FK-506 block T cell cytokine production by inhibiting activation of the NFAT transcription factor (note: different from NFkB).
Ciclosporin (INN), cyclosporine (USAN) or cyclosporin (former BAN). Image source: Wikipedia, public domain.
Together with tacrolimus, cyclosporine is a calcineurin inhibitor (CNI).
Cyclophilin. Image source: Wikipedia, public domain.
Cyclosporin is thought to bind to the cytosolic protein cyclophilin (an immunophilin) of lymphocytes, especially T-lymphocytes. This complex of cyclosporin and cyclophilin inhibits calcineurin, which under normal circumstances induces the transcription of interleukin-2.
In this study, T cells were activated in a whole blood sample and interleukin-2 producing cells were measured by cytokine staining. Regulatory T cells were analyzed by intracellular FoxP3 staining. Regulatory T cells (CD4(+)CD25(+)CD127(low)) and effector T cells (CD4(+)CD25(-)CD127(+)) were sorted by flow cytometry.
AD patients treated with low-dose CsA had a significantly larger Treg cell population than healthy controls.
Low-dose CsA therapy reduced the ability of T cells to be activated and increased Treg cells (1.6-fold change). Treg cells from AD patients had skin homing properties.
The authors concluded that the therapeutic effect of low-dose CsA therapy in AD patients might be not only mediated by the inhibition of T cell hyperactivity but also by an increased population of Treg cells.
References:
Low-dose cyclosporine A therapy increases the regulatory T cell population in patients with atopic dermatitis. Brandt C, Pavlovic V, Radbruch A, Worm M, Baumgrass R. Allergy. 2009 Apr 29. [Epub ahead of print].
Cyclosporine and FK-506 block T cell cytokine production by inhibiting activation of the NFAT transcription factor (note: different from NFkB).
Ciclosporin (INN), cyclosporine (USAN) or cyclosporin (former BAN). Image source: Wikipedia, public domain.
Together with tacrolimus, cyclosporine is a calcineurin inhibitor (CNI).
Cyclophilin. Image source: Wikipedia, public domain.
Cyclosporin is thought to bind to the cytosolic protein cyclophilin (an immunophilin) of lymphocytes, especially T-lymphocytes. This complex of cyclosporin and cyclophilin inhibits calcineurin, which under normal circumstances induces the transcription of interleukin-2.
In this study, T cells were activated in a whole blood sample and interleukin-2 producing cells were measured by cytokine staining. Regulatory T cells were analyzed by intracellular FoxP3 staining. Regulatory T cells (CD4(+)CD25(+)CD127(low)) and effector T cells (CD4(+)CD25(-)CD127(+)) were sorted by flow cytometry.
AD patients treated with low-dose CsA had a significantly larger Treg cell population than healthy controls.
Low-dose CsA therapy reduced the ability of T cells to be activated and increased Treg cells (1.6-fold change). Treg cells from AD patients had skin homing properties.
The authors concluded that the therapeutic effect of low-dose CsA therapy in AD patients might be not only mediated by the inhibition of T cell hyperactivity but also by an increased population of Treg cells.
What is the molecule that tacrolimus binds to in order to exert its therapeutic effect?
(A) NFkB
(B) calcium
(C) ipraimmunophilin
(D) NFAT
(E) calcineurin
(F) calmodulin
(G) AP-1
Answer: E.
Low-dose cyclosporine A therapy increases the regulatory T cell population in patients with atopic dermatitis. Brandt C, Pavlovic V, Radbruch A, Worm M, Baumgrass R. Allergy. 2009 Apr 29. [Epub ahead of print].
Allergy and Immunology News of the Day
Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.- Do animals on the farm and in the home reduce the risk of pediatric atopy? http://is.gd/Fr3h - More evidence needed.
- It looks like "living on a farm" rather than keeping a pet was the the helpful intervention in atopy prevention: http://is.gd/Frdn
- What Google News brought today: Supreme Court nominee's brother, Dr. Juan Sotomayor, is an allergist/immunologist http://is.gd/Fbuy
- ISAAC 3: asthma more prevalent in more affluent countries, but more severe in less affluent countries. http://bit.ly/8wygH
Image source: OpenClipArt.org, public domain.
Fluticasone nasal spray reduces nasal-ocular reflex, controls allergic eye symptoms
Eye symptoms frequently occur in patients with allergic rhinitis and are among the most bothersome symptoms. Intranasal steroids have been shown to reduce ocular symptoms even though they do not reach the eye.
The aim of this study was to elucidate the mechanism for the efficacy of topical steroids in controlling allergic eye symptoms.
In 20 subjects with seasonal allergic rhinitis, nasal challenge with antigen led to sneezing, a nasonasal, and a nasal-ocular reflex.
Treatment with fluticasone nasal spray reduced sneezing, the nasonasal and nasal-ocular reflexes, and the amount of eosinophils in nasal secretions.
Fluticasone furoate, Veramyst (US) and Avamys (EU and Canada), is different from fluticasone propionate (see below). Image source: Wikipedia, public domain.
The authors concluded that a nasal-ocular reflex follows nasal challenge with allergen and that it can contribute to the ocular symptoms associated with allergic rhinitis. These findings may support a mechanism for the efficacy of topical steroids in controlling allergic eye symptoms.
Medications for Allergic Rhinitis
References:
Fluticasone furoate nasal spray reduces the nasal-ocular reflex: A mechanism for the efficacy of topical steroids in controlling allergic eye symptoms. Baroody FM, Shenaq D, Detineo M, Wang J, Naclerio RM. J Allergy Clin Immunol. 2009 May 8.
Steroid nose sprays improve eye symptoms of AR/AC - mechanism unknown, might relate to naso-ocular reflex http://goo.gl/VVt8k
Intranasal corticosteroids had a positive impact on the eye symptoms of allergic rhinitis (review of 32 trials) http://goo.gl/EAmg1
Allergic Rhinitis: A Short Review
Mind Maps: Allergic Rhinitis
Mnemonics: Allergic Rhinitis
Blog articles from AllergyNotes
The aim of this study was to elucidate the mechanism for the efficacy of topical steroids in controlling allergic eye symptoms.
In 20 subjects with seasonal allergic rhinitis, nasal challenge with antigen led to sneezing, a nasonasal, and a nasal-ocular reflex.
Treatment with fluticasone nasal spray reduced sneezing, the nasonasal and nasal-ocular reflexes, and the amount of eosinophils in nasal secretions.
Fluticasone furoate, Veramyst (US) and Avamys (EU and Canada), is different from fluticasone propionate (see below). Image source: Wikipedia, public domain.
The authors concluded that a nasal-ocular reflex follows nasal challenge with allergen and that it can contribute to the ocular symptoms associated with allergic rhinitis. These findings may support a mechanism for the efficacy of topical steroids in controlling allergic eye symptoms.
Medications for Allergic Rhinitis
References:
Fluticasone furoate nasal spray reduces the nasal-ocular reflex: A mechanism for the efficacy of topical steroids in controlling allergic eye symptoms. Baroody FM, Shenaq D, Detineo M, Wang J, Naclerio RM. J Allergy Clin Immunol. 2009 May 8.
Steroid nose sprays improve eye symptoms of AR/AC - mechanism unknown, might relate to naso-ocular reflex http://goo.gl/VVt8k
Intranasal corticosteroids had a positive impact on the eye symptoms of allergic rhinitis (review of 32 trials) http://goo.gl/EAmg1
Allergic Rhinitis: A Short Review
Mind Maps: Allergic Rhinitis
Mnemonics: Allergic Rhinitis
Blog articles from AllergyNotes
T reg cells suppress contact hypersensitivity through a CD39 adenosine-dependent mechanism in mice
Injection of regulatory T (Treg) cells into sensitized mice suppresses contact hypersensitivity (CHS) reactions by blocking the adherence of leukocytes to vascular endothelium.
Adenosine produced by Treg cells acts as a suppressive factor. In this study, adenosine or Treg cells, respectively, abrogated the adherence of effector T cells to endothelial cell (EC) in vitro.
Caffeine principal mode of action is as an antagonist of adenosine receptors in the brain. They are presented here side by side for comparison. Image source: Wikipedia, public domain.
Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) is also known as CD39. Ectonucleotidase CD39 is the source source for Treg cell-derived adenosine. Impaired adhesion of effector T cells to inflamed endothelium was induced by adenosine-mediated downregulation of expression of E- and P-selectin on the vascular endothelium.
Adhesion Molecules
Overview of adhesion molecules, 3 groups remembered by the mnemonic SIS.
Adhesion molecules, 3 groups = SIS
Selectins
Integrins
Superfamily Ig
Selectins
The name selectin comes from the words "selected" and "lectins." Selectins are a type of carbohydrate-recognizing proteins.
There are 3 groups of selectins = LEP
L-selectins, CD62L
Leukocytes
E-selectins, CD62E
Endothelial cells
P-selectins, CD62P
Platelets
Selectin E (endothelial adhesion molecule 1). Image source: Wikipedia.
The authors concluded that adenosine release by Treg cells is essential to block leukocyte adhesion to endothelium, providing a novel mechanism by which Treg cells mediate immune suppression.
Regulatory T cells - 5 groups have been described as of year 2010:
- CD4+CD25+ regulatory T cells ("classic" T regs)
- TR1 cells, CD4 cells that secrete IL-10
- Th3 cells, a subset of CD4+ cells that secrete TGF-b
- CD8+ suppressor T cells
- γ/δ T cells
Regulatory T cells - 5 groups have been described as of year 2010 (click to enlarge the image).
References:
CD4(+)CD25(+) regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism. Ring S, Oliver SJ, Cronstein BN, Enk AH, Mahnke K. J Allergy Clin Immunol. 2009 May 7. [Epub ahead of print]
Adhesion Molecules
Adenosine produced by Treg cells acts as a suppressive factor. In this study, adenosine or Treg cells, respectively, abrogated the adherence of effector T cells to endothelial cell (EC) in vitro.
Caffeine principal mode of action is as an antagonist of adenosine receptors in the brain. They are presented here side by side for comparison. Image source: Wikipedia, public domain.
Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) is also known as CD39. Ectonucleotidase CD39 is the source source for Treg cell-derived adenosine. Impaired adhesion of effector T cells to inflamed endothelium was induced by adenosine-mediated downregulation of expression of E- and P-selectin on the vascular endothelium.
Adhesion Molecules
Overview of adhesion molecules, 3 groups remembered by the mnemonic SIS.
Adhesion molecules, 3 groups = SIS
Selectins
Integrins
Superfamily Ig
Selectins
The name selectin comes from the words "selected" and "lectins." Selectins are a type of carbohydrate-recognizing proteins.
There are 3 groups of selectins = LEP
L-selectins, CD62L
Leukocytes
E-selectins, CD62E
Endothelial cells
P-selectins, CD62P
Platelets
Selectin E (endothelial adhesion molecule 1). Image source: Wikipedia.
CD markers for central vs. effector memory T cells:
Central memory T cells: CD45RA-, CD27+, CCR7+, CD62L+
Effector memory T cells: CD45RA-, CD27-, CCR7-, CD62L-
The authors concluded that adenosine release by Treg cells is essential to block leukocyte adhesion to endothelium, providing a novel mechanism by which Treg cells mediate immune suppression.
Regulatory T cells - 5 groups have been described as of year 2010:
- CD4+CD25+ regulatory T cells ("classic" T regs)
- TR1 cells, CD4 cells that secrete IL-10
- Th3 cells, a subset of CD4+ cells that secrete TGF-b
- CD8+ suppressor T cells
- γ/δ T cells
Regulatory T cells - 5 groups have been described as of year 2010 (click to enlarge the image).
References:
CD4(+)CD25(+) regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism. Ring S, Oliver SJ, Cronstein BN, Enk AH, Mahnke K. J Allergy Clin Immunol. 2009 May 7. [Epub ahead of print]
Adhesion Molecules
Blockade of platelet-activating factor (PAF) prevents peanut-induced anaphylaxis in mice
Platelet-activating factor, also known as a PAF, is a potent phospholipid activator and mediator of platelet aggregation, inflammation, and anaphylaxis. PAF is produced by a variety of cells, including neutrophils, basophils, platelets, and endothelial cells. The PAF receptor is a G-protein coupled receptor which binds platelet-activating factor.
Platelet-Activating Factor (PAF). Image source: Wikipedia, GNU Free Documentation License.
Food anaphylaxis is an acute and life-threatening systemic allergic reaction. Fatality registries place peanut as the most common culprit of fatal and near-fatal reactions in North America.
The authors investigated the impact of blocking mast cell mediators in a mouse model of peanut-induced anaphylaxis.
One week after the last sensitization, separate groups of mice were treated with either a (1) 5-lypoxygenase inhibitor, (2) a platelet-activating factor (PAF) receptor antagonist, (3) histamine receptor antagonists, or (4) a PAF receptor antagonist along with histamine receptor antagonists before peanut challenge.
Treatment targeting either leukotrienes or histamine alone had no beneficial effects. In contrast, PAF antagonism significantly attenuated the magnitude and duration of the anaphylactic reactions. Particularly, it prevented severe reactions.
Notably, combined blockade of PAF and histamine had a clearly greater beneficial effect. In fact, all but 1 mouse developed mild, if any, anaphylactic reactions.
The authors concluded that a combination therapy blocking both PAF and histamine markedly reduces the severity of peanut-induced anaphylaxis, and thus it may be a potential life-saving therapeutic approach in food-induced anaphylaxis.
References:
Concurrent blockade of platelet-activating factor and histamine prevents life-threatening peanut-induced anaphylactic reactions. Arias K, Baig M, Colangelo M, Chu D, Walker T, Goncharova S, Coyle A, Vadas P, Waserman S, Jordana M. J Allergy Clin Immunol. 2009 Apr 29.
Will Platelet-Activating Factor (PAF) be the "BNP" of Anaphylaxis?
Platelets play important roles in the late phase of the immediate hypersensitivity reaction
Platelet-Activating Factor (PAF). Image source: Wikipedia, GNU Free Documentation License.
Food anaphylaxis is an acute and life-threatening systemic allergic reaction. Fatality registries place peanut as the most common culprit of fatal and near-fatal reactions in North America.
The authors investigated the impact of blocking mast cell mediators in a mouse model of peanut-induced anaphylaxis.
One week after the last sensitization, separate groups of mice were treated with either a (1) 5-lypoxygenase inhibitor, (2) a platelet-activating factor (PAF) receptor antagonist, (3) histamine receptor antagonists, or (4) a PAF receptor antagonist along with histamine receptor antagonists before peanut challenge.
Treatment targeting either leukotrienes or histamine alone had no beneficial effects. In contrast, PAF antagonism significantly attenuated the magnitude and duration of the anaphylactic reactions. Particularly, it prevented severe reactions.
Notably, combined blockade of PAF and histamine had a clearly greater beneficial effect. In fact, all but 1 mouse developed mild, if any, anaphylactic reactions.
The authors concluded that a combination therapy blocking both PAF and histamine markedly reduces the severity of peanut-induced anaphylaxis, and thus it may be a potential life-saving therapeutic approach in food-induced anaphylaxis.
References:
Concurrent blockade of platelet-activating factor and histamine prevents life-threatening peanut-induced anaphylactic reactions. Arias K, Baig M, Colangelo M, Chu D, Walker T, Goncharova S, Coyle A, Vadas P, Waserman S, Jordana M. J Allergy Clin Immunol. 2009 Apr 29.
Will Platelet-Activating Factor (PAF) be the "BNP" of Anaphylaxis?
Platelets play important roles in the late phase of the immediate hypersensitivity reaction
Allergy and Immunology News of the Day
Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.- BBC: thymic stromal lymphopoietin (TSLP) triggers "allergic march"- 1 in 3 children with eczema go on to develop asthma http://bit.ly/mTL0F
- Suppression of GATA-3 Nuclear Import and Phosphorylation: A Novel Mechanism of Corticosteroid Action in Allergic Disease http://bit.ly/iMitE
- Primary Biliary Cirrhosis Associated with HLA, IL12A, and IL12RB2 Variants. Interleukin-12 immunoregulatory signaling axis is relevant to the pathophysiology of primary biliary cirrhosis. http://bit.ly/2u66ho
Image source: OpenClipArt.org, public domain.
Higher folate levels associated with a lower risk of atopy and wheeze
Folic acid is known to be associated with inflammatory diseases, but the relationship between folic acid and allergic diseases is unclear.
Folic acid (folate). Image source: Wikipedia, public domain.
Data were obtained from the 2005-2006 National Health and Nutrition Examination Survey in which serum folate and total IgE levels were measured in 8083 subjects 2 years of age and older.
A high total IgE level was defined as greater than 100 kU/L. Allergen-specific IgE levels were measured for a panel of 5 common aeroallergens. Atopy was defined as at least 1 positive allergen-specific IgE level.
Serum folate levels were inversely associated with total IgE levels. The odds of a high total IgE level, atopy, and wheeze decreased across quintiles of serum folate levels, indicating a dose-response relationship between serum folate levels and these outcomes.
The authors concluded that serum folate levels are inversely associated with high total IgE levels, atopy, and wheeze.
References:
Higher serum folate levels are associated with a lower risk of atopy and wheeze. Matsui EC, Matsui W. J Allergy Clin Immunol. 2009 Apr 29.
Folic acid (folate). Image source: Wikipedia, public domain.
Data were obtained from the 2005-2006 National Health and Nutrition Examination Survey in which serum folate and total IgE levels were measured in 8083 subjects 2 years of age and older.
A high total IgE level was defined as greater than 100 kU/L. Allergen-specific IgE levels were measured for a panel of 5 common aeroallergens. Atopy was defined as at least 1 positive allergen-specific IgE level.
Serum folate levels were inversely associated with total IgE levels. The odds of a high total IgE level, atopy, and wheeze decreased across quintiles of serum folate levels, indicating a dose-response relationship between serum folate levels and these outcomes.
The authors concluded that serum folate levels are inversely associated with high total IgE levels, atopy, and wheeze.
References:
Higher serum folate levels are associated with a lower risk of atopy and wheeze. Matsui EC, Matsui W. J Allergy Clin Immunol. 2009 Apr 29.
Newest member of the T helper cell family: Th17
TH17 cells produce IL-17, IL-6, TNF, and IL-22. TH17 cells are important for neutrophil recruitment and they contribute to autoimmune disorders.
After activation by cytokines, CD4(+) naive T cells differentiate into lineages of helper/effector (T(H)) and regulatory T (Treg) cells. The trusted binary system of T(H)1 and T(H)2 has been expanded to include the IL-17-producing T(H)17 cell lineage, which plays a role in immune responses to infectious agents and autoimmune diseases.
T(H)17 cells are the newest member of the T(H) cell family and are characterized by their ability to produce cytokines such as:
- IL-17
- IL-17F
- IL-22
- CCL20
T(H)17 cells contribute to host defense as effector cells that protect against extracellular bacteria. Their activities, however, are also pivotal in autoimmune diseases.
T(H)17 cells are also associated with the development of:
- allergic contact dermatitis
- atopic dermatitis
- asthma
Function of T helper cells: Antigen presenting cells (APCs) present antigen on their Class II MHC molecules (MHC2). Helper T cells recognize these, with the help of their expression of CD4 co-receptor (CD4+). The activation of a resting helper T cell causes it to release cytokines and other stimulatory signals (green arrows) that stimulate the activity of macrophages, killer T cells and B cells, the latter producing antibodies. Image source: Wikipedia, Mikael Häggström, public domain.
T(H)1 cells produce IFN-gamma and are involved in cell-mediated immunity. T(H)2 cells produce IL-4 and contribute to humoral immunity.
Acting as counter-balance, Treg cells maintain peripheral tolerance and protect the host from auto-aggressive lymphocytes. Forkhead box protein 3-positive (FOXP3(+)) Treg cells secrete TGF-beta and IL-10 and downregulate effector T cells.
T(H)17 cells generate IL-17 and play an important role in immune responses to fungi and extracellular pathogens.
Anti-IL-17 Receptor Antibody Brodalumab Helps Patients with Psoriasis - NEJM, 2012. Anti–Interleukin-17 Monoclonal Antibody Ixekizumab Improves Chronic Plaque Psoriasis - NEJM, 2012.
Autosomal dominant hyper-IgE syndrome, a rare primary immunodeficiency disorder, is caused by mutations of signal transducer and activator of transcription 3 (STAT3), preventing T(H)17 lineage differentiation and increasing susceptibility to Staphylococcus and Candida species infections.
Mutations in the FOXP3 gene interfere with Treg cell development and cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).
Lymphoid tissue inducer-like cells and natural killer-like cells, termed RORgammat(+)NKp46(+) or NK-22 cells, might also play a role in allergic diseases because of their propensity to produce IL-17 and IL-22.
References
Development and function of TH17 cells in health and disease. Louten J, Boniface K, de Waal Malefyt R. J Allergy Clin Immunol. 2009 May;123(5):1004-11.
Development and function of TH17 cells in health and disease. Louten J, Boniface K, de Waal Malefyt R. J Allergy Clin Immunol. 2009 May;123(5):1004-11.
Interleukin-17 levels related to severity of allergic rhinitis
Anti–Interleukin-17 Monoclonal Antibody Ixekizumab Improves Chronic Plaque Psoriasis - NEJM, 2012.
After activation by cytokines, CD4(+) naive T cells differentiate into lineages of helper/effector (T(H)) and regulatory T (Treg) cells. The trusted binary system of T(H)1 and T(H)2 has been expanded to include the IL-17-producing T(H)17 cell lineage, which plays a role in immune responses to infectious agents and autoimmune diseases.
T(H)17 cells are the newest member of the T(H) cell family and are characterized by their ability to produce cytokines such as:
- IL-17
- IL-17F
- IL-22
- CCL20
T(H)17 cells contribute to host defense as effector cells that protect against extracellular bacteria. Their activities, however, are also pivotal in autoimmune diseases.
T(H)17 cells are also associated with the development of:
- allergic contact dermatitis
- atopic dermatitis
- asthma
Function of T helper cells: Antigen presenting cells (APCs) present antigen on their Class II MHC molecules (MHC2). Helper T cells recognize these, with the help of their expression of CD4 co-receptor (CD4+). The activation of a resting helper T cell causes it to release cytokines and other stimulatory signals (green arrows) that stimulate the activity of macrophages, killer T cells and B cells, the latter producing antibodies. Image source: Wikipedia, Mikael Häggström, public domain.
T(H)1 cells produce IFN-gamma and are involved in cell-mediated immunity. T(H)2 cells produce IL-4 and contribute to humoral immunity.
Acting as counter-balance, Treg cells maintain peripheral tolerance and protect the host from auto-aggressive lymphocytes. Forkhead box protein 3-positive (FOXP3(+)) Treg cells secrete TGF-beta and IL-10 and downregulate effector T cells.
T(H)17 cells generate IL-17 and play an important role in immune responses to fungi and extracellular pathogens.
Anti-IL-17 Receptor Antibody Brodalumab Helps Patients with Psoriasis - NEJM, 2012. Anti–Interleukin-17 Monoclonal Antibody Ixekizumab Improves Chronic Plaque Psoriasis - NEJM, 2012.
Autosomal dominant hyper-IgE syndrome, a rare primary immunodeficiency disorder, is caused by mutations of signal transducer and activator of transcription 3 (STAT3), preventing T(H)17 lineage differentiation and increasing susceptibility to Staphylococcus and Candida species infections.
Mutations in the FOXP3 gene interfere with Treg cell development and cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX).
Lymphoid tissue inducer-like cells and natural killer-like cells, termed RORgammat(+)NKp46(+) or NK-22 cells, might also play a role in allergic diseases because of their propensity to produce IL-17 and IL-22.
Which cytokines promote neutrophil tissue inflammation?
(A) IL-2
(B) IL-5
(C) IL-8
(D) IL-10
(E) IL-17
Answers: IL-8 and IL-17.
Development and function of TH17 cells in health and disease. Louten J, Boniface K, de Waal Malefyt R. J Allergy Clin Immunol. 2009 May;123(5):1004-11.
Development and function of TH17 cells in health and disease. Louten J, Boniface K, de Waal Malefyt R. J Allergy Clin Immunol. 2009 May;123(5):1004-11.
Interleukin-17 levels related to severity of allergic rhinitis
Anti–Interleukin-17 Monoclonal Antibody Ixekizumab Improves Chronic Plaque Psoriasis - NEJM, 2012.
Sarcoidosis is a Th1/Th17 multisystem disorder, Thorax 2011.
Pimecrolimus may be more suitable for long-term treatment of atopic dermatitis than steroids
Genetic defects leading to skin barrier dysfunction are recognized as risk factors for atopic dermatitis (AD). It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens.
The study investigated the effect of 2 common treatments, a calcineurin inhibitor (pimecrolimus) and a corticosteroid, on the skin barrier in 15 patients with AD. The patients were treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks.
Pimecrolimus. Image source: Wikipedia, public domain. Tacrolimus is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.
Betamethasone was superior in reducing clinical symptoms and epidermal proliferation; however, it led to epidermal thinning.
Both betamethasone and pimecrolimus improved clinical and biophysical parameters of AD. Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD.
A suggested approach to topical treatment of moderately severe atopic dermatitis.
References:
Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. Jensen JM, Pfeiffer S, Witt M, Bräutigam M, Neumann C, Weichenthal M, Schwarz T, Fölster-Holst R, Proksch E. J Allergy Clin Immunol. 2009 May;123(5):1124-33.
Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis. Allergy, 2011.
Drugs acting on immunophilins: Cyclosporine, Tacrolimus, Sirolimus
50% of school children with eczema (atopic dermatitis) may actually have allergic contact dermatitis (study) http://goo.gl/Bq3ZB
Atopic Dermatitis: A Short Review
The study investigated the effect of 2 common treatments, a calcineurin inhibitor (pimecrolimus) and a corticosteroid, on the skin barrier in 15 patients with AD. The patients were treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks.
Pimecrolimus. Image source: Wikipedia, public domain. Tacrolimus is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.
Betamethasone was superior in reducing clinical symptoms and epidermal proliferation; however, it led to epidermal thinning.
Both betamethasone and pimecrolimus improved clinical and biophysical parameters of AD. Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD.
A suggested approach to topical treatment of moderately severe atopic dermatitis.
References:
Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. Jensen JM, Pfeiffer S, Witt M, Bräutigam M, Neumann C, Weichenthal M, Schwarz T, Fölster-Holst R, Proksch E. J Allergy Clin Immunol. 2009 May;123(5):1124-33.
Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis. Allergy, 2011.
Drugs acting on immunophilins: Cyclosporine, Tacrolimus, Sirolimus
50% of school children with eczema (atopic dermatitis) may actually have allergic contact dermatitis (study) http://goo.gl/Bq3ZB
Atopic Dermatitis: A Short Review
Twitter notes from Peter Barnes' lecture about asthma therapy
Peter Barnes is Professor of Thoracic Medicine and Head of Airway Disease at the National Heart and Lung Institute and Honorary Consultant Physician at Royal Brompton Hospital, London. He has published over 1000 peer-review papers on asthma, COPD and related topics and has edited over 40 books. He is also amongst the top 50 most highly cited researchers in the world and has been the most highly cited clinical scientist in the UK and the most highly cited respiratory researcher in the world over the last 20 years.
These are some of my notes from his recent lecture on asthma therapy to the Nebraska Allergy Society, posted on Twitter via text messages:
Interleukin-7 receptor (IL7R)
Interleukin 7 receptor (IL7R), also known as CD127 (Cluster of Differentiation 127), is a type I cytokine receptor. Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands.
Type I cytokine receptors are mediated through JAK/STAT and bind: IL-2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, GM-CSF.
Key steps of the JAK-STAT pathway. Image source: Wikpedia, public domain.
IL7R plays a critical role in the V(D)J recombination during lymphocyte development. A defect in IL-7RA leads to SCID (T-/B+/NK+).
Thymic stromal lymphopoietin (TSLP)
Thymic stromal lymphopoietin (TSLP) signals through a heterodimeric receptor complex composed of the TSLP receptor and the IL-7R alpha chain. Some researchers have classified TSLP as a "master regulator" of the Th2 response due to overexpression of the cytokine in pulmonary tissue and skin cells result in Th2-induced asthma and dermatitis.
TSLP is produced mainly by non-hematopoietic cells as fibroblasts, epithelial cells and different types of stromal cells.
Anti-TSLP is a potential new therapeutic target in asthma.
References:
Professor Peter J Barnes. Imperial College London.
These are some of my notes from his recent lecture on asthma therapy to the Nebraska Allergy Society, posted on Twitter via text messages:
- Peter Barnes believes formoterol is a superior drug to salmeterol, unique for asthma therapy, provides quick relief, better compliance. He thinks the future of asthma therapy is SMART - Symbicort, regular use plus prn, he says they don't use Advair anymore.
- Proposed triple therapy for asthma - ICS/LABA/LAMA (long acting muscarinic antagonist). Unfortunately LAMA doesn't work that well in asthma.
- Peter Barnes: anti-IL4/IL13 didn't work for asthma, anti-IL5 is an orphan drug for rare asthma subtype - likely less than 0.01% of patients.
- New asthma therapy? - anti-TSLP (IL7 family) - works in mice.
- "We used to think the mast cell is the key cell in asthma, then chased the eosinophil, now we are back to the mast cell."
- Only 60 patients in the UK treated with omalizumab (Xolair), difficult to predict who will respond.
- Peter Barnes: PDE4 inhibitor as effective as ICS but use limited by nausea at higher doses. Doesn't work as inhalation.
- Patients like a pill for asthma - the reason behind Singulair's commercial success (it doesn't work according to Peter Barnes).
Interleukin-7 receptor (IL7R)
Interleukin 7 receptor (IL7R), also known as CD127 (Cluster of Differentiation 127), is a type I cytokine receptor. Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands.
Type I cytokine receptors are mediated through JAK/STAT and bind: IL-2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, GM-CSF.
Key steps of the JAK-STAT pathway. Image source: Wikpedia, public domain.
IL7R plays a critical role in the V(D)J recombination during lymphocyte development. A defect in IL-7RA leads to SCID (T-/B+/NK+).
Thymic stromal lymphopoietin (TSLP)
Thymic stromal lymphopoietin (TSLP) signals through a heterodimeric receptor complex composed of the TSLP receptor and the IL-7R alpha chain. Some researchers have classified TSLP as a "master regulator" of the Th2 response due to overexpression of the cytokine in pulmonary tissue and skin cells result in Th2-induced asthma and dermatitis.
TSLP is produced mainly by non-hematopoietic cells as fibroblasts, epithelial cells and different types of stromal cells.
Anti-TSLP is a potential new therapeutic target in asthma.
References:
Professor Peter J Barnes. Imperial College London.
The most influential respiratory researcher: Peter Barnes with over 26,000 citations http://goo.gl/HZh93
CD127, IL-7 receptor alpha chain
CD127, IL-7 receptor alpha chain
Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma http://goo.gl/c0vzJ
Single inhaler therapy in asthma (SMART) linked to poor day-to-day control of symptoms and increasing inflammation. Clin Exp Allergy. 2012 Jan 18.
Single inhaler therapy in asthma (SMART) linked to poor day-to-day control of symptoms and increasing inflammation. Clin Exp Allergy. 2012 Jan 18.
Monitoring adherence to ICS in asthmatic children: simple measurements by canister weight as good as electronic devices
Suboptimal adherence to inhaled steroids (ICS) is a known problem in children and adolescents, even when medications are administered under parental supervision. Poor adherence to asthma medications (less than 80%) was seen in 75% of children (JACI, 2011).In this cohort study, 102 randomly selected asthmatic children and adolescents aged 3-14 years were followed for 12 months. Adherence rate was assessed every 2 months by self and/or parent report, pharmacy dispensing data, electronic device (Doser(R); Meditrack Products, Hudson, MA, USA) monitor, and canister weight.
Adherence rates to beclomethasone (BDP) by:
- self and/or parent report - 97.9%
- pharmacy records - 70.0%
- Doser electronic device - 51.5%
- canister weight - 46.3%
Agreement analysis between (Doser) and canister weight revealed a weighted kappa equal to 0.76.
Canister weight and electronic monitoring measures were more accurate than self/parent reports and pharmacy records.
Measurements by canister weight are less costly compared with currently available electronic devices and should be considered as an alternative method of monitoring adherence to ICS.
References:
Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods. Jentzsch NS, Camargos PA, Colosimo EA, Bousquet J. Allergy. 2009 Mar 28.
Concepts have changed: “compliance” has been replaced by “adherence” but meaning remains the same: 50% of asthmatic patients are poorly adherent to therapy (http://goo.gl/3en5Q).
Image source: Metered-dose inhaler, ProAir-HFA, Albuterol Sulfate(US) - not the medication in this study. Wikipedia, public domain.
Allergy and Immunology News of the Day
Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.- Combination of oral dexamethasone and nebulized epinephrine may significantly reduce hospital admissions in bronchiolitis http://is.gd/zX10
- In children with scorpion envenomation, scorpion-specific F(ab')2 antivenom IV resolved symptoms within 4 hours http://is.gd/ALPQ
- Study: Bronchial thermoplasty decreases asthma attacks by 32% and ER visits by 84% in patients with severe asthma. http://is.gd/B76h
- The First Use of Penicillin in the United States: it looks like we remember success better than "failure" http://bit.ly/IyPBM
- The investigational antifibrotic agent pirfenidone may slow progression of idiopathic pulmonary fibrosis http://is.gd/B72y
- Social media in action: a dermatologist on Twitter/YouTube/blog/site http://is.gd/Ay35 http://is.gd/Ay3b http://is.gd/Ay3l http://is.gd/Ay3s
Image source: OpenClipArt.org, public domain.
Embeddable Google Trends Gadget
This is an example of Embeddable Google Trends gadget:
Read more here: http://is.gd/xp10 and http://is.gd/zebt
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Read more here: http://is.gd/xp10 and http://is.gd/zebt
"Search trends are a great way to see what's popular. Use this gadget to see what people are searching for on your own website.
Google Trends is based on search query volume and is updated daily."
Children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at even higher rates than with RSV
Bronchiolitis is a common disease in infancy most commonly caused by respiratory syncytial virus (RSV, also known as human pneumovirus). Other viruses which may cause this illness include metapneumovirus, influenza, parainfluenza, coronavirus, adenovirus, and rhinovirus.
Recent studies have suggested that rhinovirus-associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). Respiratory tract viruses have emerged as the most frequent triggers for exacerbations in both children and adults (JACI, 2011).
Transmission electron micrograph of RSV. Source: Wikipedia, CDC, public domain.
A chest X-ray demonstrating lung hyperinflation with a flattened diaphragm and bilateral atelectasis in the right apical and left basal regions in a 16-day-old infant with severe bronchiolitis. Image source: Wikipedia, Creative Commons Attribution 2.0 License.
This study identified retrospectively all children younger than 2 years of age who were admitted to a hospital with bronchiolitis 1988-2001.
Within the first year after hospitalization, 16.6% children with non-RSV bronchiolitis developed recurrent wheezing, compared with 2.5% children with RSV bronchiolitis.
The rates of recurrent wheezing were significantly increased in the non-RSV group also within 2 years and 3 years after hospitalization.
The authors concluded that children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3-year follow-up period than do children with RSV-induced bronchiolitis.
Transmission electron micrograph of parainfluenza virus. Two intact particles and free filamentous nucleocapsid. Image source: Wikipedia, CDC, public domain.
Coronavirus. Image source: Wikipedia, public domain.
Molecular surface of a rhinovirus, showing protein spikes. Image source: Wikipedia, GNU Free Documentation License, Version 1.2.
Recent studies have suggested that rhinovirus-associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). Respiratory tract viruses have emerged as the most frequent triggers for exacerbations in both children and adults (JACI, 2011).
Transmission electron micrograph of RSV. Source: Wikipedia, CDC, public domain.
A chest X-ray demonstrating lung hyperinflation with a flattened diaphragm and bilateral atelectasis in the right apical and left basal regions in a 16-day-old infant with severe bronchiolitis. Image source: Wikipedia, Creative Commons Attribution 2.0 License.
This study identified retrospectively all children younger than 2 years of age who were admitted to a hospital with bronchiolitis 1988-2001.
Within the first year after hospitalization, 16.6% children with non-RSV bronchiolitis developed recurrent wheezing, compared with 2.5% children with RSV bronchiolitis.
The rates of recurrent wheezing were significantly increased in the non-RSV group also within 2 years and 3 years after hospitalization.
The authors concluded that children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3-year follow-up period than do children with RSV-induced bronchiolitis.
Transmission electron micrograph of parainfluenza virus. Two intact particles and free filamentous nucleocapsid. Image source: Wikipedia, CDC, public domain.
Coronavirus. Image source: Wikipedia, public domain.
Molecular surface of a rhinovirus, showing protein spikes. Image source: Wikipedia, GNU Free Documentation License, Version 1.2.
Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children. http://goo.gl/PghX
References:
Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen H, Waris M, Ruohola A, Ruuskanen O, Heikkinen T. Allergy. 2009 Mar 23.
References:
Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen H, Waris M, Ruohola A, Ruuskanen O, Heikkinen T. Allergy. 2009 Mar 23.
Robert Merritt Chanock - Paediatrician and virologist who identified human respiratory syncytial virus. The Lancet http://goo.gl/64X3
A simple clinical prediction rule identifies healthy newborns at risk of RSV Bronchiolitis in Healthy Newborns http://goo.gl/EVlSi
Rhinoviruses: markers of, or causative for, recurrent wheeze and asthma? ERJ 2012.
Bronchiolitis, from Wikipedia, the free encyclopedia.
Rhinoviruses: markers of, or causative for, recurrent wheeze and asthma? ERJ 2012.
Bronchiolitis, from Wikipedia, the free encyclopedia.
Decrease in allergen-specific IgE as percentage of total IgE predicts the efficacy of anti-IgE (Xolair) treatment
Some patients (30%) with allergic asthma treated with anti-IgE (Xolair) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. Omalizumab binds to Cε3 region of IgE.
The role of IgE and mast cells in allergy. Image source: Wikipedia, public domain.
In this study the amount of cat allergen-specific IgE antibody was measured as a percentage of total IgE in cat allergic patients treated with the recommended doses of Xolair. Results were measured as changes in basophil allergen threshold sensitivity.
The authors concluded that significant efficacy of anti-IgE (Xolair) treatment can be predicted when Xolair decreases the amount of cat allergen-specific IgE to less than 1% of total IgE. Xolair effect was insufficient if cat allergen-specific IgE was more than 3-4% of total IgE.
References:
The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment. Johansson SG, Nopp A, Oman H, Ankerst J, Cardell LO, Grönneberg R, Matsols H, Rudblad S, Strand V, Stålenheim G. Allergy. 2009 Apr 14. [Epub ahead of print]
The role of IgE and mast cells in allergy. Image source: Wikipedia, public domain.
In this study the amount of cat allergen-specific IgE antibody was measured as a percentage of total IgE in cat allergic patients treated with the recommended doses of Xolair. Results were measured as changes in basophil allergen threshold sensitivity.
The authors concluded that significant efficacy of anti-IgE (Xolair) treatment can be predicted when Xolair decreases the amount of cat allergen-specific IgE to less than 1% of total IgE. Xolair effect was insufficient if cat allergen-specific IgE was more than 3-4% of total IgE.
References:
The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment. Johansson SG, Nopp A, Oman H, Ankerst J, Cardell LO, Grönneberg R, Matsols H, Rudblad S, Strand V, Stålenheim G. Allergy. 2009 Apr 14. [Epub ahead of print]
Allergy and Immunology News of the Day
Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.- Clinical Case: Systemic Allergic Reaction to Embedded Sewing Needle http://bit.ly/Opfyv
- New genetic defects Associated with a Syndrome of Immunodeficiency and Autoimmunity, from NEJM: ORAI1 -- CRAC -- STIM1 http://bit.ly/Zc1Mo
- "Alternative allergy treatment finds takers, skeptics" - just see the picture: "BAX-3000 laser" - skeptic is the least you can think of it... http://bit.ly/Jh4Mr
- "Average cough" produces 3,000 droplets and 20,000 virus particles http://is.gd/zf6Z
- JAMA Patient Page: Acute Sinusitis http://bit.ly/BaBQw
- Photo: "Hypoallergenic Flower" http://bit.ly/qrTj6
Image source: OpenClipArt.org, public domain.
Topical corticosteroids associated with increased lymphoma risk in atopic dermatitis
Atopic dermatitis (AD) has been associated with an increased risk of lymphoma.The study authors assessed the risk of lymphoma associated with AD and use of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) in a database (nested-case control study).
In the study population of 3,500,194 individuals, there were 2,738 cases of lymphoma.
AD was associated with an increased lymphoma risk (odds ratio [OR], 1.83). In patients with AD referred to a dermatologist, the OR further increased (OR, 3.72).
Topical corticosteroids (TCS) use was associated with an increased lymphoma risk (OR, 1.46). The risk increased with duration of exposure and potency of topical corticosteroids (TCS).
References:
Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom. Arellano FM, Arana A, Wentworth CE, Fernández-Vidaurre C, Schlienger RG, Conde E. J Allergy Clin Immunol. 2009 Apr 9. [Epub ahead of print]
Atopic Dermatitis: A Short Review
Proper use of corticosteroid ointments to treat eczema does not appear to damage or thin skin over time (study). WebMD, 2011.
Image source: Wikipedia, public domain.
Image source: Wikipedia, public domain.
TBX21 gene variants (responsible for T-bet) may increase childhood asthma risk
T-box 21, also known as TBX21, is a human gene for T-bet transcription factor. T-bet is a bridge between innate and adaptive immunity (http://buff.ly/1aD6h8s).
The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because it induces the differentiation of T(H)1 and blocks T(H)2 commitment. TBX21 works together with the homeobox transcription factor HLX1.
The TBX21 gene was resequenced in 37 adult volunteers. The impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model.
Single-nucleotide polymorphism: DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/T polymorphism). Image source: Wikipedia, David Hall, Creative Commons Attribution 2.5 License.
Forty-three polymorphisms were identified in the TBX21 gene. Three single nucleotide polymorphisms increased childhood asthma risk significantly.
In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold.
References:
TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants. Suttner K, Rosenstiel P, Depner M, Schedel M, Pinto LA, Ruether A, Adamski J, Klopp N, Illig T, Vogelberg C, Schreiber S, von Mutius E, Kabesch M. J Allergy Clin Immunol. 2009 Apr 9. [Epub ahead of print]
Genetics Suggest Asthma Is Not One Disease But "Umbrella" Term for Multiple Conditions
2 new asthma susceptibility genes: ORMDL3 and CHI3L1
The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because it induces the differentiation of T(H)1 and blocks T(H)2 commitment. TBX21 works together with the homeobox transcription factor HLX1.
The TBX21 gene was resequenced in 37 adult volunteers. The impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model.
Single-nucleotide polymorphism: DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/T polymorphism). Image source: Wikipedia, David Hall, Creative Commons Attribution 2.5 License.
Forty-three polymorphisms were identified in the TBX21 gene. Three single nucleotide polymorphisms increased childhood asthma risk significantly.
In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold.
SNPs associated with atopic diseases
Filaggrin gene
Filaggrin is essential for epidermal barrier function. SNP associated with eczema and asthma.
17q12-21 gene
ORMDL3 protein defects associated with asthma.
5q22-32 gene
CD14 is a lipopolysaccharide (LPS) receptor. SNPs associated with asthma and atopy.
3p21-22 gene
CCR5 is a chemokine receptor. SNP can be protective against asthma.
Xp22 gene
TLR7 and TLR8 are recognition receptors for viral ssRNA. SNPs assciated with asthma, rhinitis, atopic dermatitis.
5q31 gene
IL-13 is a cytokine that induces IgE secretion, mucus production, and collagen synthesis (fibrosis). SNPs associated with asthma.
ADRB2 gene
ADRB2 gene encodes β2-adrenergic receptor. Argenteum (Arg) or Arg/Arg phenotype associated with decreased albuterol response compared to Gly/Gly phenotype at residue 16.
ADAM33 gene
Type 1 transmembrane protein involved in cell-to-cell interactions. SNPs associated with asthma.
GLCCI1 gene, rs37972 variant
A variant in the glucocorticoid-induced transcript 1 gene (GLCCI1), rs37972, associated with a decrease in forced expiratory volume in 1 second (FEV1) in response to treatment with inhaled glucocorticoids (NEJM, 09/2011).
GLCCI1 gene, rs37972 variant
A variant in the glucocorticoid-induced transcript 1 gene (GLCCI1), rs37972, associated with a decrease in forced expiratory volume in 1 second (FEV1) in response to treatment with inhaled glucocorticoids (NEJM, 09/2011).
References:
TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants. Suttner K, Rosenstiel P, Depner M, Schedel M, Pinto LA, Ruether A, Adamski J, Klopp N, Illig T, Vogelberg C, Schreiber S, von Mutius E, Kabesch M. J Allergy Clin Immunol. 2009 Apr 9. [Epub ahead of print]
Genetics Suggest Asthma Is Not One Disease But "Umbrella" Term for Multiple Conditions
2 new asthma susceptibility genes: ORMDL3 and CHI3L1
Nonallergic rhinitis converts to allergic rhinitis over time
Once allergy has been ruled out, most patients with nonallergic rhinitis (NAR) are not followed up in allergy clinics, despite the persistence of rhinitis symptoms.A sample of 180 patients diagnosed with NAR during 2000-2004 was re-evaluated in 2007 by using:
- questionnaires
- spirometry
- skin prick testing
- specific IgE to common aeroallergens
Patients with NAR experienced worsening disease (52%), with an increase in the persistence (12%) and severity of nasal symptoms (9%) and new comorbidities (24%) over time.
The most frequent comorbidities at the re-evaluation were asthma (increasing from 32% to 55%) and conjunctivitis (from 28% to 43%), followed by chronic rhinosinusitis.
Sensitization to aeroallergens not present at the initial evolution was detected by means of skin prick testing, serum specific IgE measurement, or both in 24% of the patients.
The authors concluded that rhinitis associated with asthma, conjunctivitis, and sensitization to aeroallergens is likely to appear at a later date in adults initially given diagnoses of NAR.
A periodic allergy re-evaluation of patients with NAR might be necessary.
Treatment Options for Allergic Rhinitis (click to enlarge the image).
References:
Evolution of patients with nonallergic rhinitis supports conversion to allergic rhinitis. Rondón C, Doña I, Torres MJ, Campo P, Blanca M. J Allergy Clin Immunol. 2009 Apr 9.
Allergic and Non-Allergic Rhinitis Guidelines Updated
Allergic Rhinitis
Allergic Rhinitis and Conjunctivitis
Japanese guideline for allergic rhinitis: An evidence-based step-by-step strategy for treatment is described. Allergol Int. 2011 Mar;60(2):171-89.
Nonallergic rhinitis, CCJM 2012 review.
Image source: Illustration for "Aquiline or Roman Nose", Wikipedia, GNU Free Documentation License.
Stress may worsen asthma by inducing resistance to anti-inflammatory properties of glucocorticoids
Stress is known to worsen the course of asthma, but the underlying mechanisms are poorly understood.Remembering that there is a yin and yang to everything helps us resolve the paradox between production of stress-induced cortisol, which is an anti-inflammatory hormone, and worsening of asthma:
1. Stress elicits secretion of cortisol -- a hormone that generally dampens airway inflammation and ameliorates asthma symptoms.
2. However, stress could also induce resistance to the anti-inflammatory properties of glucocorticoids.
In a study of 67 children with asthma and 76 healthy children, questionnaires asked about support from their parents.
Peripheral Blood Mononuclear Cells (PBMCs) were collected and incubated with a mitogen cocktail in physiologic concentrations of hydrocortisone. Production of IL-5, IL-13, and IFN-γ was measured by ELISA.
Children with asthma who perceived low support from their parents were more resistant to hydrocortisone's anti-inflammatory effects on IL-5 and IFN-γ production and had higher circulating levels of eosinophil cationic protein.
References:
Parental support and cytokine activity in childhood asthma: The role of glucocorticoid sensitivity. Gregory E. Miller et al. JACI, Volume 123, Issue 4, Pages 824-830 (April 2009).
Stress and acquired glucocorticoid resistance: A relationship hanging in the balance. Rosalind J. Wright. JACI, Volume 123, Issue 4, Pages 831-832 (April 2009).
Chronic stress at work can make you sick
Image source: Cortisol, Wikipedia, public domain.
Farm exposure as "immunotherapy" against allergic diseases
Maternal farm exposure decreases the risk of allergic disease in the offspring.Offspring of farming mothers have:
- higher number and more efficient function of regulatory T cells (T-reg cells that express CD4, CD25 and Foxp3)
- lower TH2 cytokine secretion (IL-5) and lymphocyte proliferation
Interleukin 5. Image source: Wikipedia, public domain.
Maternal exposure to an increasing number of farm animals and stables exerts effects on both Treg cells and TH1/TH2 cells.
Even noncontinuous exposure to farm animals has an effect of higher TH1 and increased IFN-gamma secretion.
One speculation is that maternal farm exposure may result in a “natural model of immunotherapy or prophylaxis” protecting the child from developing allergic diseases.
Children living on a farm are at reduced risk of asthma (OR 0.68), hay fever (OR, 0.43), atopic dermatitis (OR, 0.80), and atopic sensitization (OR, 0.54) http://goo.gl/qVY2G
References:
Farm exposure—a novel natural model of immunotherapy against allergic diseases? JACI, Apr 2009.
Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. Bianca Schaub et al. JACI, Volume 123, Issue 4, Pages 774-782.e5 (April 2009).
How to reduce your risk of asthma: spend your whole life on a farm
Children living on farms exposed to a wider range of microbes leading to lower asthma risk. NEJM, 2011.
Protective role of contact with livestock and farming lifestyle on asthma, in particular during childhood. ERJ January 1, 2012 vol. 39 no. 1 67-75.
Image source: OpenClipArt.org, public domain.
Allergy and Immunology News of the Day
Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.- World Asthma Day is May 5, 2009 (the first Tuesday of May) http://bit.ly/NskI6 - improve asthma awareness and care around the world
- Obese children and adolescents are 26 percent more likely to have some kind of allergy, especially to food http://is.gd/wHzt
- Vitamin D Insufficiency Linked to Asthma Severity, Medscape: http://is.gd/w1IS
- Individuals with the lowest serum folate levels were 31% more likely to have atopy and 40% more likely to wheeze http://is.gd/vRoH
- ENT expanding into pulmonologists/allergists' domain:"Inclusion of Asthma in Otolaryngologic Clinical Practice" by ENToday http://is.gd/w1OO
- Easy Way to Ease Infant Immunization Pain: give the less painful vaccine first, most painful - last http://is.gd/wHyT
Image source: OpenClipArt.org, public domain.
IVIG Replacement May be Helpful in Immunoglobulin (Ig) G Subclass Deficiency
The efficacy of treating patients who have immunoglobulin (Ig) G subclass deficiency and/or antibody deficiency with Ig-replacement therapy has been debated. There are no clear guidelines.
Antibody function: each antibody binds to a specific antigen; an interaction similar to a lock and key. Image source: Wikipedia.
The authors studied 10 adult patients with recurrent respiratory infections and IgG subclass and/or antibody deficiency.
All patients received monthly Ig IV for 12 months and then were observed for 3 months without IgIV infusions.
Monthly IgIV significantly improved quality of life, decreased the number of infections and the need for antibiotics, and improved IgG subclass and antibody serum levels.
The authors concluded that Ig IV could be beneficial in patients with IgG subclass or antibody deficiency
References:
Efficacy of Intravenous Gammaglobulin for Immunoglobulin G Subclass and/or Antibody Deficiency in Adults. Abdou NI, Greenwell CA, Mehta R, Narra M, Hester JD, Halsey JF. Int Arch Allergy Immunol. 2009 Feb 12;149(3):267-274.
Antibody function: each antibody binds to a specific antigen; an interaction similar to a lock and key. Image source: Wikipedia.
The authors studied 10 adult patients with recurrent respiratory infections and IgG subclass and/or antibody deficiency.
All patients received monthly Ig IV for 12 months and then were observed for 3 months without IgIV infusions.
Monthly IgIV significantly improved quality of life, decreased the number of infections and the need for antibiotics, and improved IgG subclass and antibody serum levels.
The authors concluded that Ig IV could be beneficial in patients with IgG subclass or antibody deficiency
References:
Efficacy of Intravenous Gammaglobulin for Immunoglobulin G Subclass and/or Antibody Deficiency in Adults. Abdou NI, Greenwell CA, Mehta R, Narra M, Hester JD, Halsey JF. Int Arch Allergy Immunol. 2009 Feb 12;149(3):267-274.
Use of omalizumab (Xolair) anti-IgE therapy beyond asthma
Multiple studies have demonstrated the efficacy and safety of the monoclonal anti-IgE antibody omalizumab (Xolair) in treating patients with asthma. Omalizumab binds to Cε3 region of IgE. The use of omalizumab for other allergic diseases has been demonstrated in small studies and case reports:
- Allergic rhinitis - effective
- Immunotherapy - adds safety to immunotherapy
- Food allergy - effectiveness shown with different formulation of anti-IgE (TNX-901) than omalizumab
- Atopic dermatitis - conflicting evidence. Serum IgE levels are typically increased in atopic dermatitis - there is often difficulty in significantly reducing extremely increased IgE levels.
- Chronic urticaria/angioedema Idiopathic, autoimmune, cholinergic, cold induced. Approximately 50% of patients with chronic urticaria have an autoimmune component. Case reports show promise but there is no conclusive evidence.
- Nasal polyposis/sinusitis - improvement of edema
- Eosinophilic gastrointestinal diseases - decreased serum eosinophil counts and improved symptoms
- Drug allergy - one case report of insulin allergy
References:
Anti-IgE therapy: Clinical utility beyond asthma. Thomas B. Casale, Jeffrey Stokes. Volume 123, Issue 4, Pages 770-771.e1 (April 2009).
Single-dose omalizumab (300mg) in patients with H1-antihistamine–refractory chronic idiopathic urticaria leads to improvement within 1-2 weeks. JACI, 2011.
Single dose of omalizumab (one 300 mg injection) relieves chronic idiopathic urticaria refractory to H1-antihistamines. Medscape, 2011.
Down regulation of high-affinity IgE receptor in successful treatment of chronic idiopathic urticaria with omalizumab http://goo.gl/cHKjJ
Image source: Wikipedia, public domain.
Image source: Wikipedia, public domain.
Diet rich in nuts, seeds, olives, and wine decreases risk of asthma attacks
Varraso and colleagues analyzed dietary and asthma data from more than 1000 French women with asthma.The aim of the study was to determine dietary patterns and investigate their association with asthma incidence, current asthma and frequent asthma exacerbations.
Three dietary patterns were identified:
- the "prudent" pattern (fruits and vegetables)
- the "Western" pattern (pizza/salty pies, dessert and cured meats)
- the "nuts and wine" pattern - a diet rich in nuts, seeds, olives, and wine
No association of dietary patterns was observed with asthma incidence, ever-asthma or current asthma.
The Western pattern was associated with an increased risk of reporting frequent asthma attacks (odds ratio (OR) 1.79).
Increasing scores of the nuts and wine pattern were associated with a decreased risk of reporting frequent asthma attacks (OR 0.65).
References:
Dietary patterns and asthma in the E3N study. R. Varraso et al. Eur Respir J 2009; 33:33-41.
A high-fat meal augments neutrophilic airway inflammation, suppresses bronchodilator recovery in asthma. JACI, 2011.
Image source: A bowl of kalamata olives. Wikipedia, GNU Free Documentation License.
Image source: A bowl of kalamata olives. Wikipedia, GNU Free Documentation License.
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