Presentation at 3rd GRF One Health Summit 2015 Session Plenary II

1. The asthma epidemic: How
did we come to worldwide
300 Million patients?
Ioana Agache
Transylvania University Brasov Romania

2. Disclosure
In relation to my presentation, I declare no conflict of
interest

3. Current situation – asthma prevalence
2008- 2010 : 334 millions
Global Burden of Disease Study
2000- 2002: 235 millions

4. Asthma affects both affluent and poor countries
Prevalence of asthma symptoms among 13-14
years old (ISAAC)
Lai CKW, et al. Thorax 2009

5. Uncontrolled asthma
Prevalence of asthma symptoms in the last 12 months
among 18-45 years old in 70 countries (World Health Survey)
To T, et al. BMC Public Health 2012

6. Severe asthma
Prevalence of severe asthma among 13-16 years
old (ISAAC)
Lai CKW, et al. Thorax 2009

7. Asthma deaths
WHO Detailed Mortality
Database, updated Feb 2014

8. The Burden of Asthma (YLDs)
YLD = years lived with disability
Vos T et al. Lancet 2015; 386:743-800

9. Current situation - summary
no available therapeutic regimens can cure
asthma
rates of deaths due to asthma worldwide have
reduced greatly over the past 25 years, however
they are still high in low income countries
the burden of asthma will continue to be driven
by increasing prevalence

10. Q1. What are the risk factors for asthma

11. Global Burden of Disease Study
2013 (data from 188 countries, comprehensive
methodology for risk factors)
Incomplete methodological approach
Murray C, et al. Lancet published online Sep 11, 2015

12. Global Burden of Disease Study - methodology
Murray C, et al. Lancet published online Sep 11, 2015

13. Global Burden of Disease Study – risk factors
Murray C, et al. Lancet published online Sep 11, 2015

14. Global Burden of Disease Study – risk factors
Murray C, et al. Lancet published online Sep 11, 2015

15. Incomplete methodological approach
Associations are reported between a wide range
of risk factors and childhood asthma in
observational studies which cannot substantiate
causality
Few risk factors have been assessed in primary
prevention studies and these failed because of
bulk selection of patients

16. Incomplete methodological approach
There is no single exposure which seems likely
to cause asthma
Single exposures are invariably contaminated
by other exposures.

17. Risk factors associated with asthma
The hygiene hypothesis (mainly related to atopy)
Obesity/diet/lifestyle
Genetic background
Environmental tobacco smoke and other
pollutants
Atopy
Occupational exposure
Pet ownership

19. The hygiene hypothesis is not new

20. The hygiene hypothesis – the farm effect

21. The hygiene hypothesis – the farm effect
den Dekker HT, et al. Chest. 2015;148(3):607-17.

22. The hygiene hypothesis – the farm effect

23. What is the protective factor?

24. What is the protective factor?

25. What is the protective factor?
Smit LA et al, Clin Exp Allergy. 2007;37(11):1602-8.

26. What is the protective factor?

27. Personal and home cleanliness
Weber J, et al. AJRCCM. 2015;191:522-529
Perinatale Asthma Umwelt Langzeit Allergie Studie
(PAULA) birth cohort

28. Smoking increases the risk of asthma by 1.6
King M.E, Mannino D.M, Holguin F. Panminerva Medica 2004; 46: 97-110

29. Postnatal parental smoking increases
the risk of asthma with 20%
Burke H et al. Pediatrics. 2012;129(4):735-44

30. Maternal smoking
Continued maternal smoking during pregnancy was
associated with increased risks of early and
persistent wheezing (OR: 1.24) and asthma (OR:1.65)
den Dekker HT, et al. Chest. 2015;148(3):607-17.
prospective cohort study among 6,007 children
paternal and maternal smoking during pregnancy
(never, first trimester only, continued)
secondhand tobacco smoke exposure during
childhood

31. Maternal smoking – transgenerational effect
Li YF, et al. Chest. 2005;127(4):1232-41
In utero exposure to maternal smoking was
associated with increased risk for asthma diagnosed
in the first 5 years of life, and for persistent asthma
(OR 1.5)
Grandmaternal smoking during the mother's fetal
period was associated with increased asthma risk in
her grandchildren (OR 2.1)

32. Outdoor pollution increases asthma
incidence in adults
Jacquemin B et al. Environ Health Perspect. 2015;123(6):613-216

33. Obesity and asthma
Weinmayr G, et al. Plos One 2014; 9(12):e113996

34. Obesity and
asthma
Weinmayr G, et al. Plos One 2014;
9(12):e113996

35. A dietary basis for inflammatory diseases
interactions between
dietary or bacterial
metabolites and
immune cells and
pathways for gut
homeostasis.
Thorburn AN, et al. Immunity 2014;40:834-842.

36. A dietary basis for inflammatory diseases
Palmer DJ, et al. Immunol Allergy Clin N Am 2014;40:825-837.

37. Emerging risk factors
Inference from other preventive strategies
The indoor environment (dampness, ventilation)
Maternal fatty acid status and low vitamin D
during pregnancy
Prenatal exposures to persistent organic
pollutants or stress
Climate change

38. Climate change

39. Kunzli N, et al. Am J Respir Crit Care Med. 2006;174(11):1221-8

40. Inference from other preventive strategies
folic acid supplementation in the first trimester
only or first trimester and later had increased
relative odds of asthma
retrospective cohort study of 104,428 children,
born 1996-2005
the association folic acid supplementation and
childhood asthma at ages 4.5-6 years.
folic acid supplementation around conception
helps prevent neural tube defects
Veeranki SP, et al. Epidemiology. 2015 Sep 10. [Epub ahead of print]

41. Q2. When do these risk factors intercede

42. Asthma risk factors journey
Genetic factors Epigenetic factors
Early window of risk (the prenatal environment)
Acquired risk factors (obesity/diet, pets,
indoor and outdoor pollution/occupational)
The cumulated risk of severe asthma
complex interactions of lung structure and function genes
with environmental exposures

43. Douwes J at el. Eur Respir J. 2008 ;32(3):603-11
Early window of opportunity and
persistent exposure

44. Saskatchewan Rural Cohort Study Group
• 30.6% - early farm living (first year of life) only
• 34.4% - both early and current farm living
• 17.4% had never lived on a farm
• women had a decreased risk for both asthma and
hay fever with an early farm exposure only
• men currently living on a farm without an early
farm exposure had an increased risk for ever
asthma
Early window of opportunity and gender
Rennie DC et al. J Asthma. 2015 Sep 17:1-9. [Epub ahead of print]

45. Q3. What can we do to prevent asthma
2. Address specific risk factors (atopy)
Allergen immunotherapy (AIT)
3.Promote excellence in care
4.Raise awareness at a societal and political level
1. Focus on measures with potential to improve
lung and general health

46. 1. Focus on measures with potential to
improve lung and general health
Reduce smoking
and ETS
Reduce indoor and
outdoor air pollution
and occupational exposures
Improve feto-maternal health
Community level
Reduce social inequalities
Educational level
Reduce childhood obesity;
encourage a diet high in
vegetables and fruit
Promote breastfeeding
Reduce smoking
and ETS

47. AIT in allergic rhinitis prevents asthma
The PAT study
Long term efficacy of AIT
The German real life study
2. Address specific risk factors

48. AIT in allergic rhinitis prevents asthma
The PAT study
Jacobsen L et al. Allergy. 2007;62(8):943-8.

49. AIT in allergic rhinitis prevents asthma
The German real life study
data from German National Health Insurance
cohort of 118,754 patients with AR and without
asthma who had not received AIT in 2005
risk of incident asthma from 2007 to 2012
Schmitt J et al. J Allergy Clin Immunol. 2015 Sep 11. pii: S0091-6749(15)01101-X.
doi: 10.1016/j.jaci.2015.07.038. [Epub ahead of print])

50. The German real life study
only 2.1% received AIT
Schmitt J et al. J Allergy Clin Immunol. 2015 Sep 11. pii: S0091-6749(15)01101-X.
doi: 10.1016/j.jaci.2015.07.038. [Epub ahead of print])
the preventive effect was demonstrated only for the
SC route and was stronger for AIT > 3 years
the risk of incident asthma was significantly less in
patients exposed to AIT (RR = 0.60)

51. 3. Promote excellence in care
High quality guidelines for clinical practice
National Asthma Strategies in countries responding to the Global Asthma
Network Survey

52. 4. Increase awareness

53. Take home messages
A better understanding of the factors that cause
asthma is urgently needed
This knowledge needs to be translated into
public health and primary prevention measures
effective worldwide.
Think outside the box:
WHO: relevant risk factors for the
causation of asthma
WHAT: types of novel primary prevention
strategies developed
HOW: research methods used to provide
the evidence base for their implementation