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Karl Landsteiner Institut für Klinische und Experimentelle
Pneumologie
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Abteilung für Atemwegs-und Lungenerkrankungen
Krankenhaus Hietzing
Sigmund Freud Universität
AM ANFANG HEUSCHNUPFEN
AM ENDE ASTHMA?
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DISCLOSURES
ASTRA ZENECA
ALMIRALL
BOEHRINGER INGELHEIM
CHIESI
GILEAD
MEDA
MENARINI
NOVARTIS
TEVA
GRANTS and/or PERSONAL FEES in the last 5 years
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Rhinitis and asthma: Evidence for respiratory system integration Alkis Togias
(J Allergy Clin Immunol 2003; 111: 1171-83)
A model to illustrate the relationships between allergic rhinitis and asthma. The basic premise is that the 2 conditions are manifestations of one syndrome in 2 parts of the respiratory tract. We refer to this syndrome as the chronic allergic respiratory syndrome. The horizontal axis represents the severity of the syndrome, whereas the vertical axis represents the severity of each of the syndrome’s components (ie, allergic rhinitis and asthma). The tracings represent the relationship between syndrome severity and the severity of each component. Individuals with only allergic rhinitis are at the low end of the wide severity spectrum of the syndrome.
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Rhinitis and onset of asthma: a longitudinal population-based study Rafea Shaaban
Lancet 2008; 372: 1049–57
Cumulative incidence of asthma by year of follow-up in 3161 individuals in the control group, 704 who had atopy alone, 1377 who had non-allergic rhinitis, and 1217 who had allergic rhinitis.
Cumulative incidence rate of asthma
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Comparison between Nasal and Bronchial Inflammation in Asthmatic and Control Subjects
PASCAL CHANEZ, ANTONIO M. and JEAN BOUSQUET (AJRCCM 1999; 159: 588–595)
EG2 immunoreactivity of a nasal (a and c) and a bronchial biopsy (b and d) taken from the same control (a and b) and untreated asthmatic subject (c and d). (a and b) In the control subject, epithelium is not shed in the nasal and bronchial biopsy and the EG2 immunoreactivity is absent. (c and d) In the untreated asthmatic, in the bronchial biopsy epithelium is shed, whereas in the nasal biopsy it is almost intact. Eosinophils (EG2 immunoreactivity) are similar in numbers and in microscopic features. The thickness of the reticular basement membrane is increased in the bronchial biopsy. Original magnification: x 400.
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Impact of allergic rhinitis on asthma: effects on spirometric
Parameters G. Ciprandi, I. Cirillo, A. Pistorio
Allergy 2008: 63: 255–260
Relationship between rhinitis duration (years) and FEV1 (panel A) and FEF25–75 (panel B).
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Asthma transition from childhood into adulthood Oliver Fuchs, Thomas Bahmer, Klaus F Rabe, Erika von Mutius
Lancet Respir Med 2016; Published Online: September 22, 2016
Determinants of disease course across asthma transition and ages
This figure displays putative determinants that affect the disease course of different asthma phenotypes by course and time of onset. AHR=airway hyper-responsiveness. W.Pohl 16
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Rhinosinusitis and asthma: the missing link Anne E. Dixon
Current Opinion in Pulmonary Medicine 2009, 15: 19–24
Potential opportunities for intervention in the development of asthma?
Opportunity for intervention ?
Eczema
Opportunity for intervention ?
Allergic rhinitis
Asthma
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The Bridge to Improve Asthma Control
„Guideline Directed“ Personalized Health
Treatable Traits
and
W.Busse 17-21 June 2017, Helsinki, Finland
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Phenotypes in Asthma
Evolving Concepts of Asthma Marc Gauthier, Anuradha Ray, and Sally E. Wenzel Am J Respir Crit Care Med. 2015; 192: 660–668
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?
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#5-Reslizumab: male, age 44
• Medical history:
Asthma bronchiale since 2011, OCS (12,5 mg)
continuously for months with recurrent increases up to
50mg Aprednislone; worsening 2-3 times/month;
hospitalization 12/2016; 01-06/2016 Xolair-therapy with
no efficiency; St. p. 2x FESS, Eos: 600/μl (2015).
• Weight: 84kg
• Asthma-Medication:
Foster 3-0-3, Spiriva Respimat 2-0-0, Singulair 0-0-1,
Xyzall, Berodual, Aprednislone 37,5 mg, Dymista 1-0-1.
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#5-Reslizumab: male, age 44
0
0,5
1
1,5
2
2,5
3
3,5
0
5
10
15
20
25
30
35
40
FE
V1 [
L]
daily O
CS
(m
ean
per w
eek) [
mg
]
Association of lung function and use of OCS
OCS
FEV1
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3,22
2,81
1,81
0,56
0,83 0,84
0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
Chronic Sinusitis
+ Nasal Polyps
All Chronic Sinusitis Overall
Placebo Reslizumab (3 mg/kg IV Q4W)
54%
Frequency of asthma exacerbations over 52 weeks
83% 70%
n=72 n=78 n=129 n=123
Ad
juste
d C
AE
rate
RR 0.17 (0.10, 0.32)
RR 0.30 (0.20, 0.44)
n=476 n=477
RR 0.46 (0.37, 0.58)
CI: confidence interval; RR: rate ratio (95% CI)
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Personalized Therapeutic Approaches in Severe Asthma (E.Bleecker, ATS 2017)
Phenotype and biomarker evaluation
Biomarker Evaluation:
Allergy sensitization evaluation: Skin Prick Testing or
Radioallergosorbent testing
Total IgE level Complete blood count with differential
Airway (Sputum)cell counts Fraction of exhaled nitric oxide
Novel Biomarkers (Periostin, DPP4, Eotaxin,…) „Omic“ and pharmacogenetic approaches
Evaluate adherence to NAEPP steps 5-6 medications
Phenotype Evaluation:
Spirometry BO response Asthma control
Persistent asthma symptoms Asthma history e.g. age of Asthma onset,
family history of asthma Exacerbations including steroid bursts and
healthcare utilization Comorbidities e.g. GERD, severe sinus disease,
obesity, OSA, recurrent LRTI High resolution VT imaging
Confirm diagnosis of severe asthma
Antigens
Airway Epithelial and Goblet Cells
Severe Allergic Phenotype Severe Eosinophilic Phenotype
Severe Asthma with Physiologic Impairment
Severe Neutrophilic Phenotype ??
IL-4, IL-13
AMG 317 IL-4Rα
B-Cell
IgE
Mast-Cell
Seasonal exacerbations, sensitization, high IgE
Lebrikizumab Tralokinumab Dupilumab
IL-4Rα
Th2-Cell
Omalizumab CRTH2 (PGDE)
IL-5
Dupilumab IL-4
IL-4 IL-13
Lebrikizumab Tralokinumab Dupilumab
Mepolizumab Reslizumab Benralizumab
Benralizumab 5Rα
Eosinophil
Evidence of eosinophilic inflammation with or without evidence of atopy
APC
Anti IL-23
Th17-Cell
IL-17
Tezepelumab Anti IL-33
Airway Smooth Muscle
LAMA, LABA Bronchial Thermoplasty IL-17R Anti IL-17
LAMA
Airway Epithelial and Goblet cells
Airway remodeling, Smooth muscle hypertrophy, Mucus hypersecretion
IL-8
Neutrophil
Anti-CXCR 1/2
SCH 527123
Airway pathogens
IL-6, IL-8
Non-allergic asthma. May have low degree of eosinophilic inflammation
Macrolide
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JANINE ANTONI (1964) Chocolate and Soap National Gallery of Art Washington
