Teoria higienista en la prevención de enfermedades respiratorias alérgicas. Posición de defensa de la Teoría Higienista, en debate realizado durante la Jornada de Patología Respiratoria celebrado en el COMB, Noviembre 2019

1. ”Hygiene
Hypothesis”
con
Josep Morera
Novembre 2019
ACTUALITZACIÓ EN CONEIXEMENTS
EN PATOLOGIA
RESPIRATÒRIA
4a edició
SALA VILANA DEL COMB
8 NOVEMBRE 2019
Directors del Curs:
Dr. A. Malet
(Centre Mèdic Teknon)
Dr. J. Morera
(Centre Mèdic Teknon)
Dr. I. Chiriac
(CAMFIC)
Organitza:
programa PRELIMINAR

2. Hay fever, hygiene,
and household size.
Strachan DP. BMJ. 1989 Nov 18;299(6710):1259-60

3. “These observations . . . could be explained if
allergic diseases were prevented by infection in
early childhood transmitted by unhygienic contact
with older siblings, or acquired prenatally . . . Over
the past century declining family size, improved
household amenities and higher standards of
personal cleanliness have reduced opportunities for
cross-infection in young families. This may have
resulted in more widespread clinical expression of
atopic disease.”
Family size, infection and atopy: the first decade of
the "hygiene hypothesis”Strachan DP. Thorax. 2000 Aug; 55 Suppl 1:S2-10.

4. The “hygiene hypothesis” for
allergic disease is a misnomer
William Parker. BMJ 2014;349
Acute appendicitis and
bathrooms in three samples
of British children.
Barker DJ, Osmond C, Golding J, Wadsworth ME.
Br Med J (Clin Res Ed). 1988 Apr 2;296(6627):956-8.

5. Human TH1 and TH2 subsets:
regulation of differentiation and
role in protection and
immunopathology.
Romagnani S. Int Arch Allergy Immunol. 1992;98(4):279-85. Review.

6. The magnitude of the effect of smaller family
sizes on the increase in the prevalence of
asthma and hay fever in the United Kingdom
and New Zealand.
Wickens K1, Crane J, Beasley R. J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):554-8.
Conclusions: Changes in family size over the last 30
years do not appear to explain much of the
reported increase in asthma or hay fever
prevalence. The contribution that other risk factors
have made to these increases could be assessed
with use of a similar approach.

7. The precipitation of asthma by
upper respiratory infections.
Busse WW Chest. 1985 Jan;87(1 Suppl):44S-48S
The relationship between
viral infections and onset of
allergic diseases and asthma.
Busse WW. Clin Exp Allergy. 1989 Jan;19(1).

8. Increased risk of pneumonia and bronchiolitis
after bacterial colonization of the airways as
neonates.Vissing NH,. Am J Respir Crit Care Med. 2013 Nov 15;188(10):1246-52.
Is childhood wheeze and asthma in Latin America
associated with poor hygiene and infection? A
systematic review.
Ardura-Garcia C1, Garner P1, Cooper PJ. BMJ Open Respir Res. 2018 Feb 22;5(1):

9. Development of allergy in children. I.
Association with virus infections.
Frick OL, German DF, Mills J.
J Allergy Clin Immunol. 1979 Apr;63(4):228-41.
Effect of respiratory and other virus
infections on IgE immunoregulation.
Frick OL. J Allergy Clin Immunol. 1986 Nov;78(5 Pt 2):1013-8.

10. Detection of pathogens by real-time
PCR in adult patients with acute
exacerbation of bronchial asthma.
Yoshii Y, Shimizu K, Morozumi M, BMC Pulm Med. 2017 Nov 22;17(1):150.
Prevalence of respiratory viruses
in wheezing children not older than
24 months of age.
Bedolla-Barajas M1, Montero H2, Gac Med Mex. 2017 May-Jun;153(3):329-334.

11. Too clean, or not too clean: the
hygiene hypothesis and home hygiene.
Bloomfield SF1, Stanwell-Smith R, Crevel RW, Pickup J.
Clin Exp Allergy. 2006 Apr;36(4):402-25.
Scientists debunk idea that rise in
allergic diseases is due to homes
becoming "too clean”
Limb M. BMJ. 2012 Oct 3;345
Asthma and the hygiene hypothesis.
Does cleanliness matter?
Weber J1, Illi S, Nowak D, Schierl R, Holst O, von Mutius E, Ege MJ.
Am J Respir Crit Care Med. 2015 Mar 1;191(5):522-9.

12. Asthma and the hygiene hypothesis.
Does cleanliness matter?
Weber J1, Illi S, Nowak D, Schierl R, Holst O, von Mutius E, Ege MJ.
Am J Respir Crit Care Med. 2015 Mar 1;191(5):522-9.
Scientists debunk idea that
rise in allergic diseases is due
to homes becoming "too
clean"Limb M. BMJ. 2012 Oct 3;345

13. Inner-city asthma.
The epidemiology of an emerging
US public health concern.
under 18 years old, US asthma hospitalization rates have
demonstrated dramatic increases" of4.5% per annum during
the 19805.5 Rates for children increased during a time when
total hospitalization rates for children decreased." In re-
sponse to these disturbing epidemiologic trends, reductions
in US asthma hospitalization rates have been targeted as a
national objective," and a National Asthma Education Pr0-
gram (NAEP)-whose goal is to improve asthma care in the
United States-has been established."
A key aspect to many of the recent epidemiologic studies
of asthma has been the identification of subpopulations at
higher risk for morbidity. Among the highest risk subpopu-
lations are raciaVethnic minorities, who are both poor and
reside in the certain urban envtronments.w-" In this report,
the epidemiologic studies that have defined the problem of
asthma in the inner city will beexamined, and directions in
which new research and changes in clinical practice may
positively impact upon this high risk population will be
explored.
GEOGRAPHIC VARlATiONS IN ASTHMA
The special problems of managing asthma in poor urban
populations in the United States have been noted for
decades,":" Only recently, however, have population-based
studies begun to elucidate the magnitude of the risk that
exists for the urban poor living in certain types of city
neighborhoods.
Studies in the world literature have reported asthma in
children and adolescents to be more prevalent in urban
areas as compared to rural area.5•14-18 This relationship of
asthma prevalence to urban status, however, remains some-
what equivocal. For example, a study from South Australia
found asthma prevalence among children ages 5 to 16 years
higher in rural vs urban environments.17
A study of geographic variation of all US asthma deaths
*From the Departments of Health Care Science and Medicine,
George WashIngton University Medical Center and Center for
Health PolicyResearch, George Washington University, Washing-
ton, D.C. (Dr. Weiss); the Division of Allergy, Immunology, and
Transplantation, National Institute of Allergy and Infectious Dis-
ease, National Institutes of Health, Bethesda, (Dr. Gergen); and
the Department of Pediatrics, Albert Einstein College of Medicine,
Division of General Pediatrics (Emergency Medicine), Bronx
Municipal Hospital Center, (Dr. Crain).
Reprint requests: Dr. DHCS, Rm 28-401, George Washing-
ton University, 2150 Pennsylvania Avenue NWWashington, DC
20037
mortality and hospitalization rates are not evenly distributed
among urban neighborhoods; rather extremely high rates
are concentrated in very small areas of high poverty
commonly termed "the inner city:' Small area analyses of
mortality in Chicago demonstrate that disproportionate
numbers of deaths occurred within a very few Inner-city
neighborhoods.10 As seen in Figure 1, small area analyses of
New YorkCity asthma mortality rates demonstrate similar
findings.9
Asthma mortality rates in 1 New York City
neighborhood, East Harlem, were nearly 10 times higher
thanthe average US rate. Disproportionately high mortality
rates within the inner city appear to be closely correlated
with high hospitalization rates.9
RACElETHNICIlY AND ASTHMA
The inner city in the United States is inhabited by
impoverished people who are disproportionately nonwhite.
This demography raises questions as to whether, race!
ethnicity or socioeconomic status (SES), represents themore
prominent risk factor for asthma morbidity Asthma preva-
lence varies among racialIethnic groups in the United States.
o
o 0.)6-0.11)
-. . 0.64-1.44
•
FIGURE 1. Averageannual asthma death rates per 100,000 population
among New YorkCity residents aged 6-34 years, by neighborhood,
1962-1967.
Weiss KB, Chest. 1992
Jun;101(6 Suppl):362S-67S

14. The environment and asthma
in US inner cities.
Eggleston PA. Chest. 2007 Nov;132(5 Suppl):782S-788S.

15. Patterns of asthma mortality in
Philadelphia from 1969 to 1991.
Lang DM, Polansky M. N Engl J Med. 1994 Dec 8;331(23):1542-6.

16. Asthma and poverty.
Rona RJ. Thorax. 2000 Mar;55(3):239-44.

17. The role of cockroach allergy and
exposure to cockroach allergen in causing
morbidity among inner-city children with
asthma. Rosenstreich DL, Eggleston P. N Engl J Med. 1997 May 8;336(19):1356-63.

18. Exposure to house-dust mite allergen
(Der p I) and the development of asthma
in childhood. A prospective study.
Sporik R1, Holgate ST, Platts-Mills TA, Cogswell JJ. N Engl J Med. 1990 Aug 23;323(8):502-7

19. Persistent variations in national asthma mortality, hospital
admissions and prevalence by socioeconomic status and
region in England. Gupta RP, Mukherjee M, Sheikh A, Strachan DP. Thorax.
2018 Aug;73(8):706-712.
Conclusions
Despite asthma mortality, emergency admissions and
prevalence decreasing over recent decades, England
still experiences significant SES and regional
variations. The previously undocumented inverse
relation between deprivation and mortality in the
young requires further investigation.

20. Asthma prevalence and deprivation: a
small area analysis.Salmond C, J.Epidemiol Community
Health. 1999 Aug;53(8):476-80.
Asthma in children and adolescents in
Brazil: contribution of the International
Study of Asthma and Allergies in
Childhood (ISAAC).
Solé D, Camelo-Nunes IC, Mallozi MC. Rev Paul Pediatr. 2014 Mar;32(1):114-25.

21. Combined impact of healthy lifestyle factors on
risk of asthma, rhinoconjunctivitis and eczema
in school children: ISAAC phase III.
Morales E1, Strachan D2, Asher I3, Ellwood P3, Pearce N4, Garcia-Marcos L5; ISAAC phase III study group;
ISAAC Phase Three Study Group. Thorax. 2019 Jun;74(6):531-8
This large worldwide multicentre
cross- sectional study found that
with each point added to a child’s
healthy lifestyle index (ie,
no parental smoking, child’s
healthy body mass index,
adherence to a Mediterranean diet,
physical activity and non-sedentary
behaviour), the risk of current
wheeze and reported asthma ever
fell by 13% and 11%, respectively.

22. Do fast foods cause asthma,
rhinoconjunctivitis and eczema? Global
findings from the International Study of
Asthma and Allergies in Childhood (ISAAC)
phase three.
Ellwood P, Asher MI, García-Marcos L, Williams H, Keil U, Robertson C, Nagel G; ISAAC
Phase III Study Group. Thorax. 2013 Apr;68(4):351-60.

23. Are environmental risk factors for
current wheeze in the International
Study of Asthma and Allergies in
Childhood (ISAAC) phase three due to
reverse causation?
Silverwood RJ, Rutter CE, Garcia-Marcos L, Strachan DP,; ISAAC Phase Three Study
Group. Clin Exp Allergy. 2019 Apr;49(4):430

24. At-risk children with asthma (ARC): a
systematic review. Buelo A, McLean S, Julious S, Bush A, Henderson J,
Paton JY, Sheikh A, Shields M, Pinnock H; ARC Group. Thorax. 2018 Sep;73(9):813-824.

25. Lack of evidence for a protective effect of
prolonged breastfeeding on childhood
eczema: lessons from the International Study
of Asthma and Allergies in Childhood (ISAAC)
Phase Two. Flohr C, Nagel G, Weinmayr G, Kleiner A, Strachan DP, Williams
HC; ISAAC Phase Two Study Group. Br J Dermatol. 2011 Dec;165(6):1280-9.
Probiotics: Myths or facts about
their role in allergy prevention.
Krzych-Fałta E, Furmańczyk K, Tomaszewska A, Olejniczak D, Samoliński
B, Samolińska-Zawisza U. Adv Clin Exp Med. 2018 Jan;27(1):119-124.

26. Helicobacter, Hygiene, Atopy, and
Asthma. Miftahussurur M, Nusi IA, Graham DY, Yamaoka Y.
Front Microbiol. 2017 Jun 8;8:1034.
Absence of relationships between
tuberculin responses and
development of adult asthma with
rhinitis and atopy. Li J, Zhou Z, Chest. 2008 Jan;133(1):100-6

27. Relation between house-dust endotoxin
exposure, type 1 T-cell development, and
allergen sensitisation in infants at high risk of
asthma. Gereda JE, Leung DY, MR, Liu AH. Lancet. 2000 May 13;355(9216)

28. Allergic diseases and atopic
sensitization in children related to
farming and anthroposophic lifestyle-
-the PARSIFAL study. Alfvén T, Braun-Fahrländer PARSIFAL
study group. Allergy. 2006 Apr;61(4):414-21.
Allergic disease and sensitization in
Steiner school children.
Flöistrup H, PARSIFAL Study Group. J Allergy Clin Immunol. 2006 Jan;117(1):59-66

29. Measles and atopy in
Guinea-Bissau.
Shaheen SO, Aaby P, Hall AJ, Barker DJ, Heyes CB, Shiell AW, Goudiaby A.
Lancet. 1996 Jun 29;347(9018):1792-6.
Measles infection, measles
vaccination and the effect of birth
order in the aetiology of hay fever.
Lewis SA, Britton JR. Clin Exp Allergy. 1998 Dec;28(12):1493-500.

30. Conclusions
1.- La “hygiene hypothesis”durant més d’una
dècada va seduir la comunitat mèdica generant
múltiples treballs d’investigació.
2.- Alguns punts de la“hygiene hypothesis”s’han
utilitzats per defensar l’antroposofia i les Escoles
Steiner.

31. Conclusions
3.-L’asma “inner city” i les infeccions víriques eren
elements importants que ignorava la “hygiene
hypothesis”.
4.-L’asma és una entitat multifactorial amb
interacció genètica, epigenètica i ambiental
impossible d’aplicar-li la el mètode de “la navalla
de Ockham”