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Risks for infection in patients with asthma
(or other atopic conditions)
: Is asthma more than a chronic airway disease?
Y...
Objective of this review
1. To provide examples of specific immune
dysfunction that might contribute to increased risk of
...
The prevalence of
asthma, allergic rhinitis and atopic dermatitis
Adult Children
Asthma 4.3 – 8.6% 1 2.8 – 37% 2
Allergic ...
Worldwide time trends in the prevalence of
symptoms of asthma, allergic rhinoconjunctivitis,
and eczema in childhood: ISAA...
World map showing direction of change in prevalence of
asthma symptoms for 6–7 year age-group
M Innes Asher, et al. Lancet...
World map showing direction of change in prevalence of
asthma symptoms 13–14 year age-group
M Innes Asher, et al. Lancet 2...
World map showing direction of change in prevalence of
allergic rhinoconjunctivitis symptoms for 6–7 year age-group
M Inne...
World map showing direction of change in prevalence of
allergic rhinoconjunctivitis symptoms for 13–14 year age-group
M In...
Time Trends of the Prevalence of Asthma, Rhinitis and Eczema
in Thai Children–ISAAC Phase Three
Prevalence of asthma, rhin...
Time Trends of the Prevalence of Asthma, Rhinitis and Eczema
in Thai Children–ISAAC Phase Three
Prevalence of asthma, rhin...
Relationship between
microbial colonization or infections
and atopic conditions.
Microbial
colonization
or infections
Development of
atopic conditions
Protect
 Hygiene hypothesis
Microbial
colonization
or infections
Development of
atopic conditions
Provoke
 Counter-Hygiene hypothesis
 Microbiome hy...
Microbial
colonization
or infections
Development of
atopic conditions
Reverse causality hypothesis
atopic conditions alter...
Atopic conditions and
risk of respiratory tract infections
• Gram-positive bacteria
• Gram-negative bacteria
• Other micro...
Gram-positive bacteria
• The US Advisory Committee on Immunization
Practices (ACIP) issued a recommendation in 2008
• A si...
Gram-positive bacteria
Jung JA, J Allergy Clin Immunol 2010;125:217-21.
• AD
• AR
Increased risk of
serious pneumococcal d...
• Streptococcus pyogenes
Gram-positive bacteria
Asthma Other atopic
condition
URI with
Streptococcus
pyogenes
Adjusted RR
...
• Asthma was associated with increased colonization with
Streptococcus pneumoniae and Staphylococcus aureus in
the nasopha...
Gram-negative bacteria
• Bordetella pertussis
Adjusted OR, 1.73;
95% CI, 1.12-2.67; P 5 .01
Asthma
Capili CR, et al. J All...
Viral infections
• H1N1 Influenza virus
• Asthma = the most common comorbid condition among
patients with severeH1N1 infec...
• Respiratory syncytial virus (RSV)
• Rhinovirus
Viral infections
Increased risk of viral infections
• Type of virus
• Hos...
Other microbial infections
• Mycoplasma pneumoniae
– Normal IgM responses
– Suboptimal IgG response
• Chlamydia pneumoniae...
Atopic conditions and risk of
non–respiratory tract infections
• Genitourinary tract infection
• Reactivation of latent vi...
Genitourinary tract infection
• Community-acquired E. coli BSI
Asthma Food allergy
community-acquired
E coli BSI
Adjusted ...
Reactivation of latent viral infection
• Herpes zoster
• A large retrospective cohort study showed that
Asthma = The most ...
POTENTIAL FACTORS AFFECTING
THE ASSOCIATION BETWEEN ATOPIC CONDITIONS
AND THE RISK OF MICROBIAL INFECTION
• Corticosteroid...
Influence of corticosteroid therapies on
infection risk
O’Byrne, et al
:ICSs  decreased the risk of pneumonia
HR = 0.52 ...
Immune response to influenza vaccination
in children and adults with asthma
: Effect of corticosteroid therapy
Hanania NA,...
Asthma control status or severity
and risk of infections
Worldwide severity and control of asthma in
children and adults
Rabe KF, et al. J Allergy Clin Immunol 2004;114:40-7.
Mild...
Characteristics of asthmatics
with vs. without remission
Remission
(n = 59)
No
remission
(n = 58)
Adj. OR
(95% CI)
p-value...
Microbes and mucosal immune responses
in asthma
Microbes and mucosal immune responses
in asthma
Genes
• Filaggrin gene (FLG)
• ORM-1 (yeast) like
protein3 (ORMDL3)
• A di...
Mucosal immune response to microbes
Professional APCs
cDCs T cells
pDCs IFN-α/β
Macrophages are phagocytic APCs
M1: infl...
IL-25, IL-33, TSLP and chemokines
Circle of lymphoid cells and pathways
Innate lymphoid cells
Group 1 ILCs (ILC1 and NK ce...
PAMPs and mucosal immune response
PAMPs
PRRs:
• Plasma membrane
• Cytosol
• Endosome
Cytokine
Production
Trevor T Hansel, ...
PAMPs and mucosal immune response
PAMPs
PRRs:
• Plasma membrane
• Cytosol
• Endosome
Cytokine
Production
Respiratory RNA v...
PAMPs and mucosal immune response
Allergens:
• House dust mite binds TLR4
and dectin-2
• Peanut allergen binds CTLR
CTLR
D...
POTENTIAL MECHANISMS UNDERLYING
THE ASSOCIATION BETWEEN ATOPIC CONDITIONS
AND INCREASED RISK OF MICROBIAL INFECTIONS
• Innate immunity
• Humoral immunity
• Cell-mediated immunity
POTENTIAL MECHANISMS UNDERLYING
THE ASSOCIATION BETWEEN ATOP...
Innate immunity
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimulants
Habibzay e...
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimulants
Contoli et al,
2006
Asthma...
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimulants
Plummeridge
et al, 2000
As...
Humoral immunity
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimulants
Grove et ...
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimulants
Lee et al,
1995
Asthma • D...
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimulants
Wiertsema
et al, 2007
Alle...
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimulants
Noseworthy
et al, 2005
Ast...
Asthma and Risk of Selective IgA Deficiency or
Common Variable Immunodeficiency
: A Population-Based Case-Control Study
Ur...
Mutations in the TNFRSF13B gene
(TACI gene transmembrane activator and calcium-
modulator and cyclophilin ligand interacto...
Cell-mediated immune response
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimula...
Cell-mediated immune response
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimula...
Cell-mediated immune response
Authors Atopic
conditions
Reported immunologic
abnormalities
and dysfunctions
Immune
stimula...
Summary of the mechanisms
• Impairments in innate immunity in the airways
• Decreased adaptive immune functions
IMPLICATIONS
Patient care
• Asthmatic patients aged 19 to 64 years should be
vaccinated with PPV23 regardless of their asthma
control s...
Research
Identify phenotypic clusters
of asthmatic patients
Susceptibility to infection
or immune dysfunction
Only a subgr...
Public health
• Public health surveillance and the epidemiology of
a broad range of microbial infections.
• The effects of...
What do we know?
• Patients with asthma and
other atopic conditions
Increased risks of
Serious and Common
Infections
• Res...
What is still unknown?
• The molecular mechanism for
How atopic conditions impair immune functions?
• Clinical features a...
Thank you
Risks for infection in patients with asthma
Risks for infection in patients with asthma
Risks for infection in patients with asthma
Risks for infection in patients with asthma
Risks for infection in patients with asthma
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Risks for infection in patients with asthma

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Risks for infection in patients with asthma

Presented by Suvanee Charoenlap, MD.

Published in: Health & Medicine
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Risks for infection in patients with asthma

  1. 1. Risks for infection in patients with asthma (or other atopic conditions) : Is asthma more than a chronic airway disease? Young J. Juhn, MD, MPH J ALLERGY CLIN IMMUNOL, VOL 134, NUMBER 2, AUGUST 2014 Presented by.. Suvanee Charoenlap , MD.
  2. 2. Objective of this review 1. To provide examples of specific immune dysfunction that might contribute to increased risk of infection in patients with asthma. 2. To recognize asthma of all severities as a risk factor for respiratory and nonrespiratory tract infections.
  3. 3. The prevalence of asthma, allergic rhinitis and atopic dermatitis Adult Children Asthma 4.3 – 8.6% 1 2.8 – 37% 2 Allergic rhinitis 7 – 24% 5-8 2 – 45% 2 Atopic dermatitis 8 – 18% 4 1 – 22% 2,3 1. To T, et al. BMC Public Health 2012;12:204. 2. Asher MI, et al. Lancet 2006;368:733-43. 3. Joseph AO,et al. J Allergy Clin Immunol 2009;124:1251-8.e23. 4. Vartiainen E, et al. J Allergy Clin Immunol 2002;109:643-8. 5. Zhang Y, et al. Allergy Asthma Immunol Res 2014;6:105-13. 8. Meltzer EO, et al. Allergy Asthma Proc 2012;33(suppl 1):S113-41.
  4. 4. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys
  5. 5. World map showing direction of change in prevalence of asthma symptoms for 6–7 year age-group M Innes Asher, et al. Lancet 2006; 368: 733–43
  6. 6. World map showing direction of change in prevalence of asthma symptoms 13–14 year age-group M Innes Asher, et al. Lancet 2006; 368: 733–43
  7. 7. World map showing direction of change in prevalence of allergic rhinoconjunctivitis symptoms for 6–7 year age-group M Innes Asher, et al. Lancet 2006; 368: 733–43
  8. 8. World map showing direction of change in prevalence of allergic rhinoconjunctivitis symptoms for 13–14 year age-group M Innes Asher, et al. Lancet 2006; 368: 733–43
  9. 9. Time Trends of the Prevalence of Asthma, Rhinitis and Eczema in Thai Children–ISAAC Phase Three Prevalence of asthma, rhinitis, rhinoconjunctivitis and eczema symptoms (percentage) in ISAAC Phase I and Phase III studies. Trakultiwakorn M., et al. Journal of Asthma, 44:609–611, 2007
  10. 10. Time Trends of the Prevalence of Asthma, Rhinitis and Eczema in Thai Children–ISAAC Phase Three Prevalence of asthma, rhinitis, rhinoconjunctivitis and eczema symptoms (percentage) in ISAAC Phase I and Phase III studies. Trakultiwakorn M., et al. Journal of Asthma, 44:609–611, 2007
  11. 11. Relationship between microbial colonization or infections and atopic conditions.
  12. 12. Microbial colonization or infections Development of atopic conditions Protect  Hygiene hypothesis
  13. 13. Microbial colonization or infections Development of atopic conditions Provoke  Counter-Hygiene hypothesis  Microbiome hypothesis
  14. 14. Microbial colonization or infections Development of atopic conditions Reverse causality hypothesis atopic conditions alter susceptibility to microbial colonization or infections.
  15. 15. Atopic conditions and risk of respiratory tract infections • Gram-positive bacteria • Gram-negative bacteria • Other microbial infections
  16. 16. Gram-positive bacteria • The US Advisory Committee on Immunization Practices (ACIP) issued a recommendation in 2008 • A single dose of PPV23 to Asthmatic patients aged 19 to 64 years Asthma • Invasive pneumococcal disease • Pneumococcal pneumonia The Center for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 2010;59:1102-6. Juhn YJ, J Allergy Clin Immunol 2008;122:719-23.
  17. 17. Gram-positive bacteria Jung JA, J Allergy Clin Immunol 2010;125:217-21. • AD • AR Increased risk of serious pneumococcal disease (Adjusted OR,2.13; 95%CI, 1.04-4.35) Asthma or other atopic conditions Higher rates of tympanostomy tube placement than those • without asthma (RR 1.53; 95% CI, 0.93-2.53) or • without other atopic conditions (RR 1.70;95% CI, 1.01-2.86) Bjur KA, et al. Allergy Asthma Proc 2012;33:289-96.
  18. 18. • Streptococcus pyogenes Gram-positive bacteria Asthma Other atopic condition URI with Streptococcus pyogenes Adjusted RR (95%CI) 1.40 (1.12-1.74) 1.36 (1.07-1.66) Frey D, Jacobson R, Poland G, Li X, Juhn Y. Allergy Asthma Proc 2009;30:540-5. Juhn YJ, Frey D, Li X, Jacobson R. Prim Care Respir J 2012;21:153-8.
  19. 19. • Asthma was associated with increased colonization with Streptococcus pneumoniae and Staphylococcus aureus in the nasopharynx. • Increased risk of Staphylococcus aureus colonization of the skin in patients with atopic dermatitis Gram-positive bacteria Cernelc D, Gerbec M, Cernelc P. Acta Allergol 1975;30:423-33. Graham PL 3rd, Lin SX, Larson EL. Ann Intern Med 2006;144:318-25. Halablab MA, Hijazi SM, Fawzi MA, Araj GF. Epidemiol Infect 2010;138:702-6. Warner JA, McGirt LY, Beck LA. Br J Dermatol 2009;160:183-5. Leung A, Schiltz A, Hall C, Liu A. Clin Exp Allergy 2008;38:789-93. Leung DY. Curr Opin Pediatr 2003;15:399-404.
  20. 20. Gram-negative bacteria • Bordetella pertussis Adjusted OR, 1.73; 95% CI, 1.12-2.67; P 5 .01 Asthma Capili CR, et al. J Allergy Clin Immunol 2012;129:957-63. • Legionella pneumophila • Community-acquired Escherichia coli bloodstream infection (BSI) • Pseudomonas aeruginosa Boldur I, Beer S, Kazak R, Kahana H, Kannai Y. Isr J Med Sci 1986;22:733-6. Bang DW, et al. BMJ Open 2013;3:1-8. Beisswenger C, et al. J Immunol 2006;177:1833-7.
  21. 21. Viral infections • H1N1 Influenza virus • Asthma = the most common comorbid condition among patients with severeH1N1 infection (hospitalization or death), with rates of asthma ranging from 10% to 32%. Asthma Other atopic condition H1N1 Influenza Adjusted RR (95%CI) 4 (1.8-9.0) 1.89 (1.15-3.12) Kloepfer KM, et al. Am J Respir Crit Care Med 2012; 185:1275-9. Santillan S, Mehra S, Pardo Crespo MR, Juhn YJ. Allergy Asthma Proc 2013;34:459-66.
  22. 22. • Respiratory syncytial virus (RSV) • Rhinovirus Viral infections Increased risk of viral infections • Type of virus • Host’s immunogenetics • Environmental factors Atopic conditions Holt PG, Sly PD. Nat Med 2012;18:726-35.
  23. 23. Other microbial infections • Mycoplasma pneumoniae – Normal IgM responses – Suboptimal IgG response • Chlamydia pneumoniae Asthma The potential negative effect of a TH2-biased response on immunity  Leishmaniasis, Toxoplasmosis, Schistosomiasis, and Candidiasis Smith-Norowitz TA, et al. Pediatr Infect Dis J 2013;32:599-603.
  24. 24. Atopic conditions and risk of non–respiratory tract infections • Genitourinary tract infection • Reactivation of latent viral infection
  25. 25. Genitourinary tract infection • Community-acquired E. coli BSI Asthma Food allergy community-acquired E coli BSI Adjusted RR (95%CI) 2.74 (1.11-6.76) 3.51 (0.94-13.1) Bang DW, et al. BMJ Open 2013;3:1-8.
  26. 26. Reactivation of latent viral infection • Herpes zoster • A large retrospective cohort study showed that Asthma = The most common chronic condition among children with herpes zoster Asthma sensitization against aeroallergens or food allergens Herpes zoster infection Adjusted RR (95%CI) 2.09 (1.24-3.52) 3 (1.09-8.25) Kim BS, et al. J Pediatr 2013;163:816-21. Tseng HF, Smith N, Marcy SM, Sy LS, Jacobsen SJ. Pediatr Infect Dis J 2009;28:1069-72.
  27. 27. POTENTIAL FACTORS AFFECTING THE ASSOCIATION BETWEEN ATOPIC CONDITIONS AND THE RISK OF MICROBIAL INFECTION • Corticosteroid therapies • Control status or severity
  28. 28. Influence of corticosteroid therapies on infection risk O’Byrne, et al :ICSs  decreased the risk of pneumonia HR = 0.52 (95% CI, 0.36-0.76) based on pooled data from many clinical trials. O’Byrne PM, et al.Am J Respir Crit Care Med 2011;183:589-95.
  29. 29. Immune response to influenza vaccination in children and adults with asthma : Effect of corticosteroid therapy Hanania NA, et al. J Allergy Clin Immunol 2004;113:717-24
  30. 30. Asthma control status or severity and risk of infections
  31. 31. Worldwide severity and control of asthma in children and adults Rabe KF, et al. J Allergy Clin Immunol 2004;114:40-7. Mild asthma are at an increased risk of infection
  32. 32. Characteristics of asthmatics with vs. without remission Remission (n = 59) No remission (n = 58) Adj. OR (95% CI) p-value Freq. of viral infections per person-years 0.3 [95% CI, 0.2-0.8] 0.4 [95% CI, 0.1-0.7] 0.60 (0.23-1.56) 0.29 Freq. of bacterial infections per person- years 0.5 [95% CI, 0.2-1.0] 0.5 [95% CI, 0.2-0.9] 0.94 (0.74-1.19) 0.49 Javed A,et al. J Asthma 2013;50:472-9 No significant differences
  33. 33. Microbes and mucosal immune responses in asthma
  34. 34. Microbes and mucosal immune responses in asthma Genes • Filaggrin gene (FLG) • ORM-1 (yeast) like protein3 (ORMDL3) • A disintegrin and metalloprotease-33 (ADAM33) Host immune response to microbes Environmental effects epigenetic changes • DNA methylation • Histone acetylation • Micro RNA activities
  35. 35. Mucosal immune response to microbes Professional APCs cDCs T cells pDCs IFN-α/β Macrophages are phagocytic APCs M1: inflammatory and T-cell activation M2: patrolling and scavenging AAM: IL-13 production in atopy (M2 subtype)
  36. 36. IL-25, IL-33, TSLP and chemokines Circle of lymphoid cells and pathways Innate lymphoid cells Group 1 ILCs (ILC1 and NK cells) -> IFN-γ Group 2 ILCs (ILC2, NH cells) -> IL-5 and IL-13 Group 3 ILCs (including ILC3) -> IL-17 and IL-22 Th2 pathway IL-3, IL-4, IL-5, IL-9, IL-13 Th1 pathway IFN-γ, TNF-β IL-17 (Th17, Tγδ) pathway IL-17A, IL-17F, IL-23 T follicular helper cells B cell Ig and IgE Cytotoxicity/cell killing • Tc • NK cells • NKT cells Immune homoeostasis and remodelling (Th22, Treg) IL-10, IL-22, TGF-β, IL-17
  37. 37. PAMPs and mucosal immune response PAMPs PRRs: • Plasma membrane • Cytosol • Endosome Cytokine Production Trevor T Hansel, et al. Lancet 2013; 381: 861–73
  38. 38. PAMPs and mucosal immune response PAMPs PRRs: • Plasma membrane • Cytosol • Endosome Cytokine Production Respiratory RNA viruses contain ssRNA and generate dsRNA replication intermediates: • Rhinoviruses • Influenza viruses • Respiratory syncytial virus Bacteria: • Lipoproteins • Lipoteichoic acid and peptidoglycan • Lipopolysaccharide • Flagellin TLRs 3, 7, 8, 9 RLRs • Type I IFN production (IFN-α types and IFN-β) • Type III IFNs (3 subtypes: IFN-λ1/IL-29, IFN- λ2/IL-28A, and IFN-λ3/IL-28B) TLRs 1/2, 2/6, 4, 5 NLR family • Inflammosome complex, Inactive pro-proteins Active IL-1β and IL-18 Proinflammatory cytokines Trevor T Hansel, et al. Lancet 2013; 381: 861–73
  39. 39. PAMPs and mucosal immune response Allergens: • House dust mite binds TLR4 and dectin-2 • Peanut allergen binds CTLR CTLR Dectin-1 : fungal PAMPs Dectin-2 Trevor T Hansel, et al. Lancet 2013; 381: 861–73
  40. 40. POTENTIAL MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN ATOPIC CONDITIONS AND INCREASED RISK OF MICROBIAL INFECTIONS
  41. 41. • Innate immunity • Humoral immunity • Cell-mediated immunity POTENTIAL MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN ATOPIC CONDITIONS AND INCREASED RISK OF MICROBIAL INFECTIONS
  42. 42. Innate immunity Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Habibzay et al, 2012 HDM-sensitized mice • Impaired TLR 2– mediated signaling transduction on neutrophils • Reduced neutrophil recruitment in the airways S pneumoniae
  43. 43. Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Contoli et al, 2006 Asthma Impaired IFN-λ secretion Rhinovirus Wark et al, 2005 Asthma Impaired IFN-β secretion Rhinovirus Message et al, 2008 Asthma • Impaired TH1 cytokine secretion (IFN-γ, IL-10, and IL-12) by PBMCs • Augmented TH2 cytokine secretion (IL-4, IL-5, and IL-13) by PBMCs Rhinovirus Laza-Stanca et al, 2011 Asthma Impaired IL-15 secretion Rhinovirus Sykes et al, 2013 Asthma Well controlled No difference in • rhinovirus replication or • Induction of IFN-β or IFN- λ secretion by epithelial cells between patients with well- controlled asthma and nonasthmatic subjects Rhinovirus
  44. 44. Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Plummeridge et al, 2000 Asthma Impaired IL-12 secretion LPS (E coli) and IFN-γ Beisswenger et al, 2006 TH2 cytokine– preincubated human bronchial epithelial cells Decreased antimicrobial peptide (human β- defensin 2) secretion P aeruginosa OVA-sensitized mice • Decreased antimicrobial peptide (CRAMP) and proinflammatory cytokine (IL-1b and IL- 6) secretion • Increased TH2 cytokine (IL-4 and IL-13) secretion in the airways and number of bacteria in the lungs (BAL) P aeruginosa
  45. 45. Humoral immunity Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Grove et al, 1975 Asthma (no steroid)/atopic dermatitis (human) Decreased hemagglutinin antibody response to tetanus toxoid Tetanus toxoid vaccine
  46. 46. Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Lee et al, 1995 Asthma • Decreased antibody level against studied polysaccharide antigens both before and after vaccination • No difference in mean fold increase PPV23 Lee et al, 1995 Eczema (human [moderate/sev ere]) Decreased antibody level against pneumococcal vaccine (PPV23) PPV23 Jung et al, 2010 Asthma Decreased serotype- specific pneumococcal antibody levels against PPV23 but not pneumococcal surface protein antibody PPV23
  47. 47. Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Wiertsema et al, 2007 Alleles associated with atopy and asthma (human) • IL4 2589T, IL4 2979T, and IL4RA 551Gln associated with lower serotype-specific pneumococcal antibody responses, IgG PCV7 followed by PPV23 Zhao et al, 2013 Asthma • Inverse correlation between anti-PspC antibody levels and TH2 immune profile (IL- 5 secretion by PBMCs after stimulation with staphylococcal enterotoxin B) • Correlation modified by asthma status pneumococcal surface protein C
  48. 48. Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Noseworthy et al, 2005 Asthma Seronegative for measles (40% to 43%) and mumps (25% to 39%) Two doses of MMR vaccine Patel et al, 2013 Asthma Decreased mumps virus–specific IgG levels Single dose of MMR vaccine Yoo et al, 2014 Asthma More rapid waning of measles vaccine virus– specific IgG levels over time than in nonasthmatic subjects after 1 dose of MMR vaccination Measles vaccine virus
  49. 49. Asthma and Risk of Selective IgA Deficiency or Common Variable Immunodeficiency : A Population-Based Case-Control Study Urm SH, et al. Mayo Clin Proc 2013;88:813-21.
  50. 50. Mutations in the TNFRSF13B gene (TACI gene transmembrane activator and calcium- modulator and cyclophilin ligand interactor) are found in • 6.25% of patients with sIgAD • 8% to 21% of patients with CVID TNFRSF13B mutations 2.5-fold increased risk of asthma at 4 years independent of IgE levels Castigli E, et al. Nat Genet 2005;37:829-34. Janzi M, Melen E, Kull I, Wickman M, Hammarstrom L. Genes Immun 2012;13:59-65.
  51. 51. Cell-mediated immune response Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Fischer et al, 1997 IL-4– overexpressing mice Delayed clearance of RSV from the lung RSV Grove et al, 1975 Asthma Decreased delayed-type hypersensitivity (CMI) response to any of 5 antigens (Aspergillus fumigatus, Candida albicans, mumps skin test antigen, old tuberculin,streptokinase streptodornase) 5 antigens
  52. 52. Cell-mediated immune response Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Kim et al, 2013 Asthma Increased risk of herpes zoster against which CMI has been known to be the primary defense mechanism NA Yoo et al, 2010 Asthma Decreased lymphoproliferative response (MMR-specific T-cell response) to MMR vaccine virus Two doses of MMR vaccine
  53. 53. Cell-mediated immune response Authors Atopic conditions Reported immunologic abnormalities and dysfunctions Immune stimulants Otero et al, 2013 Asthma • Lower production of TNF-α and IFN-γ and higher production of IL-5 by PBMCs (PMA) • No differences in CMI responses after stimulating PBMCs with intact Mycobacterium tuberculosis and S pneumoniae M tuberculosis, S pneumoniae
  54. 54. Summary of the mechanisms • Impairments in innate immunity in the airways • Decreased adaptive immune functions
  55. 55. IMPLICATIONS
  56. 56. Patient care • Asthmatic patients aged 19 to 64 years should be vaccinated with PPV23 regardless of their asthma control status. • Atopic conditions  Increase risk of infections : Routine vaccinations and booster • Atopic conditions  work up : Immunoglobulin levels sIgAD and CVID
  57. 57. Research Identify phenotypic clusters of asthmatic patients Susceptibility to infection or immune dysfunction Only a subgroup  increased risk of microbial infections and immune incompetence Need to identify The effects of atopic conditions Not be limited to the airways but might be systemic
  58. 58. Public health • Public health surveillance and the epidemiology of a broad range of microbial infections. • The effects of atopic conditions on emerging or re- emerging infectious diseases at a population level are unknown
  59. 59. What do we know? • Patients with asthma and other atopic conditions Increased risks of Serious and Common Infections • Respiratory • Nonrespiratory • A subgroup of patients with asthma and other atopic conditions • Impaired innate immunity in the airways • Decreased adaptive immune functions
  60. 60. What is still unknown? • The molecular mechanism for How atopic conditions impair immune functions? • Clinical features and biomarkers for Identify patients with asthma or other atopic conditions who have increased risk of infections • Atopic conditions affect the epidemiology of emerging and re-emerging infectious diseases???
  61. 61. Thank you

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