What 2012 atopy risk protective factor

WHAT YOU SHOULD HAVE READ BUT….2012

 atopy risk &
protective factors
Attilio Boner
University of
Verona, Italy

• Prevalence and time
trends

Prenatal negative life events increases cord blood IgE:
interactions with dust mite allergen and maternal atopy.
Peters, Allergy 2012;67:545

Background: Prenatal exposure to both stress & aeroallergens
(dust mite) may modulate the fetal immune system. These exposures
may interact to affect the newborn immune response. We examined
associations between prenatal maternal stress & cord blood total IgE
in 403 predominately low-income minority infants enrolled
in the Asthma Coalition on Community, Environment and Social Stress
(ACCESS) project. We also examined potential modifying effects
of maternal atopy and maternal dust mite exposure.


1) Overall the negative
domains score was
 The Crisis in Family positively associated
Systems survey
with increased
was administered
cord blood IgE.
to mothers prenatally.
2) Cord blood IgE levels
 Negative life event increased 0.10 IU/ml
domain score was derived.
for each unit increase
 Dust mite allergen in dust in the number of negative
from pregnant mothers„ domains reported
bedrooms. by the mother.

Relationship for atopic mothers between log cord
blood IgE & n°of domains with negative life
events by high vs low dust mite allergen.

 The Crisis in Family
Systems survey
was administered
 Negative life event
 Dust mite allergen in dust
from pregnant mothers„
bedrooms.

Relationship for atopic mothers between log cord
blood IgE & n°of domains with negative life
Among children
of atopic
Systems survey
mothers, the positive
was administered
association between
stress & IgE
 Negative stronger
was life event
domain high dust mite
in the score was derived.
group.
bedrooms.

Relationship for nonatopic mothers between log
cord blood IgE & n°of domains with negative life

Systems survey
was administered
 Negative life event
bedrooms.

Relationship for nonatopic mothers between log
cord blood IgE & n°of domains with negative life
In children
 Themothers without
of Crisis in Family
Systems survey
a history of atopy,
was administered
the positive
association between
 Negative & IgE was
stress life event
most evident
in the low allergen
group.
bedrooms.


1) These data suggest that prenatal maternal stress may influence
fetal immune system development in children born to mothers
both with and without a history of atopy.
2) Moreover, the demonstration of synergistic effects
of stress & aeroallergen exposure points to the need for
a multi pronged intervention approach to reducing disease risk.

Resilience in low-socioeconomic-status children
with asthma: adaptations to stress.
Chen, JACI 2011;128:970

Background:
Low socioeconomic status (SES) is a strong predictor of many
health problems, including asthma impairment;
however, little is understood about why some patients defy this trend
by exhibiting good asthma control despite living in adverse
environments.
Objective:
This study sought to test whether a psychological characteristic,
the shift-and-persist strategy (dealing with stressors by reframing
them more positively while at the same time persisting in optimistic
thoughts about the future), protects low-SES children with asthma.

Chen, JACI 2011;128:970

 121 children aged 9 to 18 yrs
with asthma.
1) „„I thought about the
 Shift-and-persist scores.
things I was learning
 The tendency to shift oneself from the situation or
in response to stressors about something good
was measured by using the
that would come from it‟‟.
Cognitive Restructuring scale
of the Responses to Stress
questionnaire. 2) „„I always feel good about
Smith, J Consult Clin Psychol 2000;68:976. my future‟‟.
 Higher scores indicated a higher
tendency to positively reappraise
stressful situations.

Chen, JACI 2011;128:970

with asthma. Children
who came from
low-SES backgrounds
 The tendency to shift oneself but who engaged in
in response to stressors shift-and-persist strategies
displayed less asthma
inflammation at baseline
questionnaire. (p <0.05)
Smith, J Consult Clin Psychol 2000;68:976. as well as
less asthma impairment
(p <0.01)
stressful situations. at the 6-mo period.

Chen, JACI 2011;128:970

with asthma. Children
In contrast,
who came from
shift-and-persist low-SES backgrounds
 The tendency to shift oneself but who engaged in
strategies
in response to stressors shift-and-persist strategies
were not beneficial
displayed less asthma
among high-SES
inflammation at baseline
children with
questionnaire. (p <0.05)
as well as
asthma.
Smith, J Consult Clin Psychol 2000;68:976.
less asthma impairment
(p <0.01)
stressful situations. at the 6-mo period.

Allergy is associated with suicide completion with a
possible mediating role of mood disorder-a population-
based study Qin, Allergy 2011;66:658
% subjects with a history of
hospital contact for allergy
2 –

 27 096 completed
suicides.

467 571 live controls. 1 – 1.17 %
0.79 %

0
Suicide Controls

% subjects with a history of
hospital contact for allergy
2 –
We observed a
 27nonsignificantly
096 completed
stronger effect
suicides.
in women than in
men and a
467 571 live controls. 1 – 1.17 %
stronger effect 0.79 %
for individuals at
high ages
0
Suicide Controls


OR for suicide
2 –

 27 096 completed
suicides. 1.59
467 571 live controls. 1 –

0
Allergy that led
to inpatient treatment


OR for suicide
Allergy increased 2 –
suicide risk only in
 27 persons with no
096 completed
suicides.
history of mood 1.59
disorder, whereas
467 571eliminated
it live controls. 1 –
suicide risk in
those with a
history of mood
disorder. 0
Allergy that led
to inpatient treatment

Impaired type I and III interferon response to
rhinovirus infection during pregnancy and asthma
Forbes, Thorax 2012;67:209

Background:
• Acute respiratory tract infections are common ailments
to all individuals and the human rhinoviruses (HRVs) cause
most of these infections.
• Pregnant women have increased susceptibility and disease severity
to viral infections like influenza and HRVs, as do asthmatics.
• Successful pregnancy requires immunological modulation
to permit fetal tolerance.

A) Pregnant women
had significantly reduced
 1) 10 stable pregnant asthmatics; innate IFN responses
2) 10 stable not pregnant asthmatics; to HRV infection
3) 10 pregnant non-asthmatic women;
(p<0.02), persistin
4) 10 who were ≥6 mo post partum;
g ≥6 mo
5) 10 who were not pregnant.
post partum (p≤0.02).
 Peripheral blood mononuclear cells
(PBMCs) cultured with B) Pregnant asthmatics
HRV43 and HRV1B. had significantly reduced
IFNλ responses
 IFNα and IFNλ (lambda) compared with
from culture supernatants.
healthy non-pregnant women
(p≤0.034).

Interferon-α (IFNα) and IFNλ responses
of peripheral blood mononuclear cells (PBMCs) from pregnant women
to in vitro human rhinovirus (HRV) stimulation.

Isolated PBMCs from pregnant (P), postpartum (PP) and non-pregnant
healthy control (HC) women were stimulated with HRV43 or HRV1B.
= IFNα = IFNλ

of peripheral blood mononuclear cells (PBMCs) from asthmatic women

Isolated PBMCs from non-pregnant healthy control (HC) women and
asthmatics who were pregnant (PA) and not pregnant (A) were stimulated
= IFNα = IFNλ with HRV43 or HRV1B.

Reduced antiviral IFNs
of peripheral blood mononuclear asthma provide an asthmatic women
during pregnancy and cells (PBMCs) from important
mechanism for increased susceptibility, morbidity
and mortality in pregnant women with
respiratory viral infection.

Isolated PBMCs from non-pregnant healthy control (HC) women and
asthmatics who were pregnant (PA) and not pregnant (A) were stimulated
= IFNα = IFNλ with HRV43 or HRV1B.

Febrile respiratory illnesses in infancy and atopy are
risk factors for persistent asthma and wheeze
Kusel, Eur Respir J 2012;39:876
At age of 10 years % of children
60 -

 147 children at 60%
50 –
high atopic risk.
40 –
 Followed from birth
to age 10 yrs.
30 –

 Respiratory infections 20 – 26%
collected prospectively 20.4%
and viral aetiology
18%
10 –
ascertained.
000 Current Current Persistent
 Atopy wheeze and Atopic
doctor-diagnosed eczema asthma wheeze
eczema and asthma.

At age of 10 years % of children
60 -

 147 children at 60%
50 –
high atopic risk.
35.8% experienced 40 –
 Followed from lower
at least one birth
to age 10 yrs.
respiratory infection 30 –
(LRI) associated
 Respiratory infections
with fever and/or 20 – 26%
collected prospectively 20.4%
wheeze in first
and viral aetiology
18%
10 –
ascertained. life.
year of
000 Current Current Persistent
 Atopy wheeze and Atopic
doctor-diagnosed eczema asthma wheeze
eczema and asthma.

In children who had wheezy or febrile LRI in
infancy and were atopic by 2 yrs
 147 children at RR at age 10yrs for
high atopic risk. 5 -
4.92
 Followed from birth 4 - p<0.001
to age 10 yrs.
3 – 3.51
 Respiratory infections
p<0.001
collected prospectively
and viral aetiology 2 –
ascertained.
1 –
 Atopy wheeze and
doctor-diagnosed
eczema and asthma. 0 persistent current
wheeze asthma


1. Severe viral respiratory infections in infancy and early atopy
are risk factors for persistent wheeze and asthma.
2. The strongest marker of the asthmatogenic potential of
early life infections was concurrent fever.
3. The occurrence of fever during respiratory illnesses is an
important marker of risk for wheeze and asthma later in
childhood, suggesting it should be measured in prospective
studies of asthma aetiology.

Staphylococcal-derived superantigen enhances peanut
induced Th2 responses in the skin.
Forbes-Blom, Clin Exp Allergy 2012;42:305

Concomitant exposure to
Peanut extract (PE) staphylococcal-derived
superantigen

Th2 model

Th2 response in the skin draining lymph nodes


Concomitant exposure to
Peanut extract (PE) staphylococcal-derived
superantigen

Significantly enhanced
specific Th2 responses.

Th2 model
(+)

Th2 response in the skin draining lymph nodes

Exposure of staphylococcal enterotoxin B (SEB) when being primed to peanut
extract (PE) leads to an enhanced PE-dependent CD4 Th2 response.c

(a) (b)

Absolute n° (a) and proportion (b) of CD4+ GFP+ T cells present in the
draining auricular lymph node 24h after final intradermal boost.

Staphylococcal enterotoxin B compromises
the immune tolerant status in the airway mucosa.
Liu T, Clin Exp Allergy 2012;42:375

1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced
by the bacterium Staphylococcus aureus. SEB may contaminate
ingested food and induce gastrointestinal dysfunction.
SEB interferes with the function of the immune system
in the airway mucosa, such as to be involved in the pathogenesis
of airway allergy.
2) Integrin alphavbeta6 (avb6) is produced by epithelial cells
in response to external stimuli, such as wound and inflammation.
Our recent study data also show that intestinal epithelial cells
express detectable avb6 that has protelytic activity and can convert
the precursor of transforming growth factor (TGF)β into the active
form of TGFβ. TGFβ plays a critical role in the Treg development.
Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase
(ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.


1) Staphylococcal enterotoxin B (SEB) is an enterotoxin produced
by the bacterium Staphylococcus aureus. SEB may contaminate
ingested food and induce gastrointestinal dysfunction. in avb6
The increases in SEB and decreases
SEB interferes with the function of the immune system
in the airway mucosa, such as to be involvedassociated
in nasal epithelium are in the pathogenesis
of airway allergy. compromises of immune tolerance
with the
in the nasal mucosa.
2) Integrin alphavbeta6 (avb6) is produced by epithelial cells
in response SEB has stimuli,ability wound and inflammation.
to external the such as to suppress
Our recent study data also show that intestinal epithelial cells
express detectable avb6 that has protelyticavb6 and can convert
the expression of activity
in nasal epithelial cells.
the precursor of transforming growth factor (TGF)β into the active
form of TGFβ. TGFβ plays a critical role in the Treg development.
Tolergenic DCs (TolDC) express TGFβ and aldehyde dehydrogenase
(ALDH) that can induce CD4+ CD25- T cells to Foxp3+ Tregs.

Avb6 expression is suppressed in the
allergic rhinitis (AR) nasal epithelium
• The immune tolerant components,
tolerogenic dendritic cells (TolDC) P<0.01

& regulatory T cells (Treg), were
assessed in the surgically removed
nasal mucosa from patients
with allergic rhinitis (AR)
Staphylococcal enterotoxin B (SEB)
or non-AR chronic rhinitis. levels are increased in the allergic
rhinitis nasal epithelium.
• Contents of Staphylococcal
enterotoxin B & integrin alphavbeta6 P<0.01
(avb6) in the nasal epithelium
assessed using enzyme-linked
immunoassay.

Avb6 expression is suppressed in the
allergic rhinitis (AR) nasal epithelium
• The immune tolerant components,
tolerogenic dendritic cells (TolDC)
The components
P<0.01

& regulatory T cells (Treg), were
of immune tolerance
assessed in the surgically removed
machinery,
nasal mucosa from patients
with allergic rhinitisTregs
TolDCs & (AR) Staphylococcal enterotoxin B (SEB)
or non-AR chronic rhinitis.
were suppressed levels are increased in the allergic
rhinitis nasal epithelium.
in the AR
• Contents of Staphylococcal
enterotoxin B &mucosa.
nasal integrin alphavbeta6 P<0.01
(avb6) in the nasal epithelium
assessed using enzyme-linked
immunoassay.

Gram+ bacteria on grass pollen exhibit adjuvant activity
inducing inflammatory T cell responses
Heydenreich, Clin Exp Allergy 2012;42:76

Background Recently, it has been established that
pollen grains contain Th2-enhancing activities besides
allergens.
Objective The aim of this study was to analyse
whether pollen carry additional adjuvant factors like
microbes and what immunological effects they may
exert.


A complex mixture of bacteria
and moulds was detected
on grass pollen:
 Timothy pollen grains
collected and disseminated - Gram-negative that are known
on agar plates. to favour Th1-directed immune
responses.
 Immunologic effects
of microbial products - Gram positive bacteria e.g
on DC & T cell responses. Bacillus cereus & Bacillus
subtilis.
- Moulds.


Supernatants of homogenized Gram+
bacteria induce CD80, CD83 expression in
immature dendritic cells.

collected and disseminated
on agar plates.
of microbial products
on DC & T cell responses.


Supernatants of homogenized Gram+
Contact of immature bacteria induce CD80, CD83 expression in
dendritic cells (DC) immature dendritic cells.
from grass pollen allergic
 Timothy pollensupernatants
donors with grains
collected homogenized
of and disseminated
on Gram-positive bacteria
agar plates.
induced maturation of DC
as measured
by up-regulation of CD80
and CD83.


Induction of proinflammatory cytokines in
immature dendritic cells.

collected and disseminated
on agar plates.


Conclusions and Clinical Relevance These data indicate
that grass pollen is colonized by several microorganisms
that influence the immune response differently.
Similar to LPS, supernatants of homogenized
Gram-positive bacteria may serve as adjuvants
by augmenting DC maturation and inflammatory Th1, Th2
and Th17 responses helping to initiate allergic
immune responses.

Innate lymphoid cells responding to IL-33 mediate
airway hyperreactivity independently of adaptive
immunity Kim JACI 2012;129:216

Background
Asthma has been considered an immunologic disease
mediated by TH2 cells and adaptive immunity.
However, clinical and experimental observations
suggest that additional pathways might regulate
asthma, particularly in its nonallergic forms,
such as asthma associated with air pollution,
stress, obesity, and infection.
Objectives
Our goal was to understand TH2 cell–independent conditions that might
lead to airway hyperreactivity (AHR), a cardinal feature of asthma.


Glycolipid
antigens

directly induced
alveolar macrophages
1) Activate natural killer T (NKT) cells.
to produce IL-33,
as well as IL-13.

2) Airway hyperreactivity developed rapidly


Glycolipid
antigens

directly induced
Because plant pollens, house dust, andalveolar macrophages
some bacteria
1) Activate natural killer T (NKT) cells. activate NKT cells,
contain glycolipids that can directly to produce IL-33,
these studies suggest that as well as IL-13.
AHR and asthma
can fully develop or be greatly enhanced
2) Airway hyperreactivity developed rapidly
through innate immune mechanisms.

Schematic of the
IL-33–ST2 axis in the
development of AHR.
On activation by glycolipid
antigens, NKT cells induce
macrophages, DCs, and
type II pneumocytes to
produce IL-33, which in turn
activates natural helper and
NKT cells to produce IL-13,
resulting in the development
of AHR.
IL-33 can also activate mast
cells, eosinophils, and
basophils. ST2 = IL-33R = IL-33 Receptor

Gestational age at birth and risk of allergic rhinitis
in young adulthood. Crump JACI 2011;127:1173

For subjects born extremely
preterm (23-28 weeks) OR for
 630,090 infants born in
Sweden including 27,953 1.0 –
born preterm (<37 wks).

 Prescription of nasal 0.5 – 0.70
corticosteroids and oral 0.45
antihistamines 0.0
Nasal corticosteroid Both nasal
 age, 25.5-37.0 yrs. prescription corticosteroid and
oral antihistamine
prescription

Gestational age at birth and risk of allergic rhinitis
in young adulthood. Crump JACI 2011;127:1173

These findings suggest
that low gestational age For subjects born extremely
at birth independent preterm (23-28 weeks) OR for
 630,090 infants born in
of fetal growth is
Sweden including 27,953 1.0 –
associated with a
born preterm (<37 wks).
decreased risk of
 Prescription of nasal young
allergic rhinitis in
0.5 – 0.70
corticosteroids and oral
adulthood, possibly 0.45
antihistaminesa protective
because of 0.0
Nasal corticosteroid Both nasal
effect of earlier
 age, 25.5-37.0 yrs. prescription corticosteroid and
exposure to pathogens. oral antihistamine
prescription

Infant antibiotic use and wheeze and asthma risk: a
systematic review and meta-analysis
Penders ERJ 2011;38:295

OR for
2 – wheeze/asthma

 18 longitudinal studies.

 Effect of antibiotic use
on wheeze/ asthma.
1 –
1.27
Early antibiotic
use

Infant antibiotic use and wheeze and asthma risk: a
systematic review and meta-analysis
Penders ERJ 2011;38:295

When we eliminated OR for
studies with possible 2 – wheeze/asthma
reverse causation
 18 longitudinal studies.
and respiratory tract
infections leading
 Effect of antibiotic use
to antibiotic use,
on wheeze/ asthma.
the pooled risk estimate 1 –
1.27
was attenuated
to OR 1.12.
Early antibiotic
use

Prenatal or Early-Life Exposure to Antibiotics and Risk
of Childhood Asthma: A Systematic Review
Murk Pediatrics 2011;127:1125

OR for asthma if exposed to
 Studies published 3 –
antibiotic in the first yr of life
between 1950 and
July 1, 2010, that
assessed associations 2 –
between antibiotic 2.04
exposure during
1.52 1.25
pregnancy or in the 1 –
first year of life
and asthma at
ages 0 to 18 yrs. 0
all studies retrospective prospective
studies studies


 Studies published 3 –
between 1950 and
Risk estimate
July 1, 2010, that
assessed studies
for associations
2 –
between adjusted
that antibiotic 2.04
for respiratory
exposure during
1.52 1.25
pregnancy or in the
infections is 1 –
first year 1.16
OR of life
and asthma at
ages 0 to 18 yrs. 0
studies studies


 Studies published to
Antibiotics seem 3 –
between 1950 and
slightly increase
July 1, 2010, that
the risk of
assessed associations
childhood asthma. 2 –
between antibiotic
Reverse causality and 2.04
exposure during
protopathic bias seem
1.52 1.25
pregnancy possible
to be or in the 1 –
first year of life
confounders for
and asthma at
this relationship.
ages 0 to 18 yrs. 0
studies studies

The Association of Acetaminophen and Asthma
Prevalence and Severity McBride Pediatrics 2011;128:1181

• The epidemiologic association between acetaminophen use and
asthma prevalence and severity in children and adults is well
established.

• A variety of observations suggest that acetaminophen use has
contributed to the recent increase in asthma prevalence in
children:
1) the strength of the association;
2) the consistency of the association across age, geography, and
culture;
3) the dose-response relationship;
4) the timing of increased acetaminophen use and the asthma
epidemic;


established.

children:
5) the relationship between per-capita sales of acetaminophen and
asthma prevalence across countries;
6) the results of a double-blind trial of ibuprofen and
acetaminophen for treatment of fever in asthmatic children;
7) the biologically plausible mechanism of glutathione depletion in
airway mucosa.


Until future studies document the safety
of this drug, children with asthma or at
established.
risk for asthma should avoid the use of
acetaminophen.
children:
5) the relationship between per-capita sales of acetaminophen and
asthma prevalence across countries;
6) the results of a double-blind trial of ibuprofen and
acetaminophen for treatment of fever in asthmatic children;
7) the biologically plausible mechanism of glutathione depletion in
airway mucosa.

Correlation of specific IgE to shrimp with cockroach
and dust mite exposure and sensitization in an inner-city
population Wang JACI 2011;128:834
Shrimp specific IgE levels were correlated
with exposure to cockroach but only among
children with positive IgE levels to cockroach.

 504 serum samples.
 sIgE to shrimp,
cockroach
(Blattella germanica)
and
Dermatophagoides
farinae.


High exposure to
 504 serum samples.
B. Germanica in
 sIgEtheshrimp, was
to home
cockroach
significantly
andcorrelated with
Dermatophagoides IgE
higher shrimp
farinae. levels.


In contrast,
 504 high exposure
serum samples.
 sIgE to shrimpmite
to dust ,
cockroach
in the home
and
was not
correlated with
Dermatophagoides
farinae. IgE levels.
shrimp


Conclusions
•For children with evidence of IgE-mediated sensitization to
cockroach and shrimp, having high exposure to cockroach in the
home can contribute to higher shrimp IgE levels, which might not
correlate with clinical reactivity.
•Further patient evaluations with clinical histories
of shrimp exposure and reactions, as well as oral food challenges,
would have to be performed to confirm these findings.

Inhibition of house dust mite–induced allergic airways
disease by antagonism of microRNA-145 is comparable
to glucocorticoid treatment. Collison JACI 2011;128:160

 MicroRNAs (miRNAs) are important regulators of the
immune system by promoting the catabolism of their
target transcripts as well as attenuating their translation.

 Blocking miRNA function may provide a new nonsteroidal
anti-inflammatory approach to treatment.

Sensitized and then aeroallergen-
challenged with house dust mite

Allergic airways disease, and
alterations in the expression of
miRNAs: miR-145, miR-21, and let-7b

Sensitized and then aeroallergen-
challenged with house dust mite

Inhibition of miR-145, but not miR-21 or
lethal-7b, inhibited eosinophilic
inflammation, mucus hypersecretion, TH2
cytokine production, and airway
hyperresponsiveness.
Allergic airways disease, and
alterations in the expression of
miRNAs: miR-145, miR-21, and let-7b

Invariant NKT cells are required for airway inflammation
induced by environmental antigens
Wingender J Exp Med 2011;208:1151

• Recent increases in the prevalence of asthma and other allergic
diseases have prompted investigators to consider the role
of the environment in the genesis of atopy.
• We have previously reported that house dust extracts (HDEs) contain
ligands that activate DCs by toll-like receptor 2 (TLR-2)-, TLR4-, and
TRL9- dependent pathways.
Boasen J JACI 2005;116:185-191.
Batzer G Immunobiology 2007;212:491-498.
• We have further established that HDEs have the potential
to function as Th2 adjuvants in mice receiving intranasal (i.n.) OVA
vaccinations.
Ng N. JACI 2006;117:1074-1081.
Lee S.M. AJRCMB 2011;44:341-349.


• Novel invariant natural killer T cell-activating antigens
found in house dust extracts.
• Invariant natural killer T (iNKT) cells are effector cells activated
by CD1d presentation of glycolipid antigens.
• Until now, iNKT antigens have been found in 2 bacteria,
one of which is the causative agent in Lyme disease.
• We report the discovery of iNKT antigens in house dust
extracts.


• These experimental findings highlights the complexity
of house dust as an immunostimulant.
• More specifically, we provide direct evidence that living
environments have the potential to activate iNKT cells through
their T-cell receptor and potentially by other pathways,
adding support to the view that iNKT cells have clinical
relevance in human asthma and other diseases.

House dust mite extract downregulates C/EBPα* in
asthmatic bronchial smooth muscle cells
Miglino ERJ 2011;38:50
1. Increased IL-6 protein
House dust mite and proliferation of BSM
(HDM) extracts cells of asthma patients
only.
2. HDM extract reduced the
C/EBPα expression in BSM
cells of asthma patients.
3. HDM extract elicited
both protease-dependent
Bronchial smooth muscle cells and –independent
(BSM) responses.

* enhancer-binding protein

House dust mite extract downregulates C/EBPα* in
asthmatic bronchial smooth muscle cells
Miglino ERJ 2011;38:50
1. Increased IL-6 protein
House dust mite and proliferation of BSM
HDM exposure
(HDM) extracts cells of asthma patients
contributes only.
to inflammation
and remodelling 2. HDM extract reduced the
C/EBPα expression in BSM
by a nonimmune cells of asthma patients.
cell-mediated mechanism
via a direct interaction 3. HDM extract elicited
both protease-dependent
with BSM cells. and –independent
Bronchial smooth muscle cells
(BSM) responses.

* enhancer-binding protein

Playing a dirty trick on airway smooth muscle: house dust
mite does it again Zuyderduyn ERJ 2011;38:4

 Airway smooth muscle cells isolated from asthmatic
proliferate faster in culture and produce more chemokines
and an altered array of extracellular matrix proteins
compared with those of healthy individuals.
 The increase in ASM proliferation in asthma is thought to be
associated with decreased levels of CCAAT enhancer protein
(c/EBP)α (encoded by the CEBPA gene), a crucial controller of
cell cycle progression, differentiation and inflammation.


 In addition to increased proliferation, interleukin (IL)-6
release (induced by growth factors) is increased in ASM from
asthmatics.

 House dust mite (HDM) exerts direct effects on various cell
types, including protease-dependent cell detachment in
epithelial cells and IgE-independent activation of mast cells.


 Exposure of rabbit ASM strips to the purified Der p 1
allergen increased airway hyperresponsiveness
to acetylcholine and reduced relaxation responses
to isoproterenol, and this effect was attributed to the
protease activity of Der p 1.

 These data suggest that the effects of HDM can be
IgE-dependent and –independent, as well as
protease-dependent and –independent.

Antibacterial antibody responses associated with the
development of asthma in house dust mite-sensitised and
non-sensitised children. Hales, Thorax 2012;67:321

Background:
Infants who develop house dust mite (HDM) allergy
and HDM sensitised children with severe persistent asthma have
low antibody responses to the P6 antigen of Haemophilus influenzae.

Objective:
1) To measure the development of antibody to 2 ubiquitous bacteria
of the respiratory mucosa in a prospective birth cohort
at high risk of allergic disease.
2) To assess which responses are associated with asthma and atopy.

Development of IgG1 antibody
(ng/ml)
 IgG1 and IgG4 antibody to:
- H. influenzae (P4, P6)
- S. pneumoniae (PspA, PspC)
surface antigens.
 Yearly blood samples * * ** * *** * *
of children aged 1-5 yrs.
 Children were stratified
based on:
- HDM sensitisation
- Asthma * **
at 5 yrs of age.
*p<0.05, **p<0.01, ***p<0.001

(ng/ml)
HDM-sensitised children
- S. pneumoniae (PspA, PspC)
surface had lower
antigens.
IgG1 antibody titres
 to the blood samples
Yearly bacterial antigens, * * ** * *** * *
of and early responses
children aged 1-5 yrs.
 (<3yrs and before
Children were stratified
based on:development
the
of HDM sensitisation
- HDM sensitisation
- Asthma asthma).
and * **
at 5 yrs of age.
*p<0.05, **p<0.01, ***p<0.001

(ng/ml)
- S. HDM-sensitisedPspC)
pneumoniae (PspA,
surface antigens.
children
have early defective
 Yearly blood samples * * ** * *** * *
ofantibody responses
children aged 1-5 yrs.
to bacteria
 Children were stratified
that are associated
based on:
- HDM sensitisation
with asthma.
- Asthma * **
at 5 yrs of age.
*p<0.05, **p<0.01, ***p<0.001


Possible explanations
1. The low IgG antibody response could enhance atopy and asthma
by increasing the susceptibility to bacterial infection
and the exposure to pharmacologically active bacterial products.
2. Underlying immune responses to the bacteria and allergens
influence immune responses to each other when they are copresented
at the mucosa to increase the degree of sensitisation.
3. Altered antibody responses are just markers that show
people with atopy and asthma have alterations in an aspect of their
mucosal immune system that extends beyond the response to allergens.


Possible explanations
1. The low IgG antibody response could enhance atopy and asthma
by increasing the susceptibility to bacterial infection
Increased bacterial colonisation,
and the exposure to pharmacologically active bacterial products.
including both H influenzae and S pneumoniae,
2. Underlying immune responses to the bacteria and allergens
has been associated with susceptibility
influence immune responses to each other when they are copresented
at the mucosaasthma and degree of sensitisation.
to to increase the wheezing attacks.
3. Altered antibody responses are just markers that show
people with atopy and asthma have alterations in an aspect of their
mucosal immune system that extends beyond the response to allergens.

Protease-activated receptor 2-dependent fluid secretion
from airway submucosal glands by house dust mite
extract Cho JACI 2012;129:529
Background
The submucosal gland (SMG) is important in the control of airway
surface fluid.
Protease-activated receptor (PAR) 2 contributes to the pathophysiology
of allergies in response to nonspecific allergens bearing proteases and
anion secretion.
House dust mites (HDMs) have abundant proteases that can activate
PAR2, but little is known about the direct effect of HDM on SMG
secretion.

Objective
To investigate the effect of HDMs on glandular secretion and its
mechanism in allergic patients, patients with chronic rhinosinusitis
(CRS), or both.


Inferior nasal
1) HDM induced a
turbinates.
significantly higher
55 patients classified secretion rate
into four groups:
and number of
1. the control,
2. allergic rhinitis (AR), responding glands
3. chronic rhinosinusitis (CRS), in the AR and
4. AR + CRS. AR+CRS groups
Mucus bubbles from than in the
individual submucosal control group.
gland (SMGs).


Inferior nasal 2) Patients in the
turbinates. CRS group, who had no
55 patients classified HDM-specific IgE,
into four groups: showed a
1. the control, higher response
2. allergic rhinitis (AR), than the control group,
3. chronic rhinosinusitis (CRS),
and its response
4. AR + CRS.
was suppressed by
Mucus bubbles from a PAR2-selective
individual submucosal antagonist.
gland (SMGs).

Quantitative
measurement of
glandular secretion.
A. Harvest of nasal mucosa
from the inferior nasal
turbinate.
B. Experimental setup.
C. Mucus bubbles from
glands under oil are
visualized by using
bright-field microscopy
and side-light illumination.
D. Example of mucus
bubbles formed on the
surface of nasal
turbinates 30 minutes
after stimulation.

Responses to HDM. Plots of averaged
secretion rates versus time for each group.
Inferior nasal *p < 0.05
turbinates.
55 patients classified
into four groups:
1. the control,
2. allergic rhinitis (AR),
3. chronic rhinosinusitis (CRS),
4. AR + CRS.

Mucus bubbles from
individual submucosal
gland (SMGs).


Conclusions

HDM allergens can induce glandular secretion in patients
with AR, CRS, or both, and PAR2 represents a possible
mechanism for nonspecific hyperreactivity in inflammatory
airway diseases.

Gene-by-environment effect of house dust mite on
purinergic receptor P2Y12 (P2RY12) & lung function in
children with asthma.
Bunyavanich, Clin Exp Allergy 2012;42:229

Background Distinct receptors likely exist for leukotriene (LT)E4,
a potent mediator of airway inflammation.
Purinergic receptor P2Y12 is needed for LTE4-induced airways
inflammation, and P2Y12 antagonism attenuates house dust mite
induced pulmonary eosinophilia in mice. Although experimental data
support a role for P2Y12 in airway inflammation, its role in human
asthma has never been studied.
Objective To test for association between variants in the P2Y12 gene
(P2RY12) and lung function in human subjects with asthma,
and to examine for gene-by-environment interaction with house
dust mite exposure.


Background Distinct receptors likely exist for leukotriene (LT)E4,
a potent mediator of airway inflammation.
House dust mite
Purinergic receptor P2Y12 is needed for LTE4-induced airways
inflammation, and P2Y12 antagonism attenuates house dust mite
exposure caused
induced pulmonary eosinophilia in mice. Although experimental data
significant
support a role for P2Y12 in airway inflammation, its role in human
asthma has never been studied.
gene-by-environment
Objective To test for association between variants in the P2Y12 gene
(P2RY12) and lung functioneffects.
in human subjects with asthma,
and to examine for gene-by-environment interaction with house
dust mite exposure.


•5 SNPs in P2RY12 were associated
with multiple lung function measures
 19 single nucleotide (P-values 0.006–0.025).
polimorphisms (SNPs) •Haplotypes in P2RY12 were also
associated with lung function
in P2RY12. (P-values 0.0055–0.046).
 Children with asthma (n=422) •House dust mite exposure
modulated associations between
& their parents (n=1266) . P2RY12 and lung function, with
minor allele homozygotes exposed to
 Associations between house dust mite demonstrating
these SNPs & lung function. worse lung function than those
unexposed (significant interaction P-
 House dust mite exposure. values 0.0028–0.040).


Relationship
between P2RY12
single nucleotide
polymorphisms
& airways
responsiveness
stratified by
house
dust mite
exposure.
(a) House dust
mite exposure

The long-term protective effects of domestic animals
in the home. Erwin CEA 2011;41:920

 There is a critical age at which exposure to animals can have a
protective effect. Specifically, animal exposure needs to occur
in the first year of life.

 When tolerance to cats was first described, many
authors assumed that it would be comparable with
the effect of farm animals, which appears to be
dependant on an early exposure to endotoxin or
environmental microorganisms.

 But in many studies, measurements of endotoxin have not been
higher in homes with domestic animals and the effect of cat
ownership appears to be cat specific.

The long-term protective effects of domestic animals
in the home. Erwin CEA 2011;41:920

 Children living in a house with a cat can produce high levels of
IgE to mite while remaining „tolerant‟ to the cat.

 Current estimates of high exposure to cat suggest that 20–50
times more allergen is inhaled as compared with mite allergen.

 A large part of the estimated 1 μg of cat allergen inhaled per
day is swallowed.

 On this basis, daily exposure to cat, or dog,
allergens is not far different from the doses used
for sublingual „desensitization‟.

Lifetime dog and cat exposure and dog- and cat-
specific sensitization at age 18 years
Wegienka CEA 2011;41:979

 Detroit Childhood OR for sensibilization
Allergy Study birth to dog at age 18 yrs
cohort contacted at 1.0 –
the age 18 years.

 Sensitization to dog 0.5 –
or cat defined as
animal-specific
0.50
0.0
IgE ≥ 0.35 kU/L. Those with an indoor dog
during the first year of life


 Detroit Childhood OR for sensibilization
Allergy Study birth to cat at age 18 yrs
cohort contacted at 1.0 –
the age 18 years.

 Sensitization to dog 0.5 –
or cat defined as
animal-specific
0.52
0.0
IgE ≥ 0.35 kU/L. With an indoor cat in the
first year of life


 Detroit Childhood life
The first year of OR for sensibilization
Allergy Study birth
is the critical period to cat at age 18 yrs
cohort contacted at
during childhood when 1.0 –
the age 18 years. to
indoor exposure
dogs or cats 0.5 –
 Sensitization to dog
0.52
influences
or cat defined as to
sensitization
animal-specific
these animals. 0.0
IgE0.35 kU/L. With an indoor cat in the
first year of life

Risk factors for new-onset cat sensitization among
adults: A population-based international cohort study
Olivieri JACI 2012;129:420

Background
Cat exposure during childhood
has been shown to increase the risk of
developing cat sensitization, while the effect
ofcat exposure in adulthood has not yet been established.

Objective
To evaluate new-onset sensitization to cat in adulthood
in relation to changes in cat keeping.


% adults who became
6292 European sensitized to cat
4.0 –
Community Respiratory
Health Survey I
(ECRHS I)
3.5 –
3.0 –
3.7%
participants 2.5 –
(20 to 44 years).
2.0 –
Reevaluated 1.5 –
9 years later.
1.0 –
Serum IgE level 0.5 -
≥0.35 kU/L.
0.0


6292 European RR for new onset
Community Respiratory cat sensitization
Health Survey I 2.0 –
(ECRHS I)
participants 1.5 – 1.85
(20 to 44 years).
1.0 –
Reevaluated
9 years later. 0.5 -

Serum IgE level 0.0
Cat acquisition during follow-up when
≥0.35 kU/L. compared with those without a cat
at both surveys.


Conclusion
Acquiring a cat in adulthood nearly doubles the risk
of developing cat sensitization.
Hence, cat avoidance should be considered in adults, especially
in those sensitized to other allergens and reporting a history
of allergic diseases.

Effect of prenatal indoor pet exposure on the trajectory
of total IgE levels in early childhood
Havstad JACI 2011;128:880

Background
The presence of pets in a home
during the prenatal period and during early infancy has been associated with a lower
prevalence of allergic sensitization and total IgE levels in middle childhood.
No studies have examined the effect of pet exposure in a population-based cohort by
using multiple early-life measures
of serum total IgE.
Objectives
We sought to examine within-individual longitudinal trends
in total IgE levels during early childhood
and assess the effect of indoor prenatal pet exposure
on those trends.

Log-transformed IgE values
by age.

 Birth cohort.
 1187 infants.
 1 to 4 measurements of total
IgE collected from birth to 2
yrs of age.

Log-transformed IgE values
by age.


The trajectory
Birth cohort.
of IgE levels was
 1187 infants.
nonlinear, with an
accelerated
yrs increase before
of age.

6 months.


 Birth cohort.
 1187 infants.
yrs of age.


Total IgE levels
were lower across
 Birth entire early-life period
the cohort.
 1187 infants. there was
when
prenatal indoor
pet exposure
yrs of age. 0.001).
(p<


% reduction in total IgE due to pet exposure and
type of delivery.

0 –
 Birth cohort. vaginal Cesarean
 1187 infants.
-10 –
-16% section
 1 to 4 measurements of total -20 – p<0.06
yrs of age.
-30 –

-40 - -43%
p<0.001
-50 –


% reduction in total IgE due to pet exposure and
type of delivery.

0 –
 Birth cohort. vaginal Cesarean
Pet exposure and
 1187 infants.
delivery mode
-10 –
-16% section
 1 to 4 measurements of total -20 – p<0.06
might be markers
yrs infant exposure
of of age. -30 –
to distinct
microbes. -40 - -43%
p<0.001
-50 –

High environmental relative moldiness index during
infancy as a predictor of asthma at 7 years of age
Reponen Ann Allergy Asthma Immunol 2011;107:120

% children asthmatic
at the age 7 yrs
20 –
 A high-risk birth cohort
from infancy to 7 years
of age.
15 – 18%
10 –
 Mold assessed by a
DNA-based analysis for
05 –
the 36 molds.

00

High environmental relative moldiness index during
infancy as a predictor of asthma at 7 years of age
Reponen Ann Allergy Asthma Immunol 2011;107:120
aORs (95% CIs) for Asthma Diagnosis at 7 Years of Age by
Predictor Variables of the 176 Study Children

Abbreviations: aOR, adjusted odds ratio; CI, confidence interval;
ERMI, Environmental Relative Moldiness Index.
These variables remained statistically significant (P <0.05) in a full multivariate model.

Asthma related to Alternaria sensitization:
an analysis of skin-test and serum-specific IgE
efficiency based on the bronchial provocation test
Fernández CEA 2011;41:649

% pts with a (+) specific
challenge
70 –
 74 asthmatic 60 –
patients sensitized
to Alternaria .
50 – 61%
40 –
 Specific bronchial 30 –
challenge with this
20 –
mould.
10 –

.0


Skin prick testing challenge
almost perfectly 70 –
 74 asthmatic outcome
predicted the 60 –
of bronchoprovocation
patients sensitized
to Alternaria .
tests.
50 – 61%
40 –
Weals around 5.5 mm
 Specific bronchial 90%
in diameter had 30 –
challenge with this a
probability of 20 –
mould.
positive challenge.
10 –

.0


A CAP value 70 –
challenge
 74 asthmatickUA/L
≥ 16
60 –
predicted a positive
patients sensitized
tobronchial challenge
Alternaria .
50 – 61%
40 –
result with 99%
 Specific bronchial
accuracy, 30 –
challenge with this
20 –
mould.
10 –

.0

Meta-analysis of mould and dampness exposure on
asthma and allergy in eight European birth cohorts:
an ENRIECO initiative Tischer, Allergy 2011;66:1570

OR for early asthma symptoms
0,3 –

 31 742 children from 8
ongoing European birth 0.2 –
cohorts.
 Reported mould or 1.39
dampness exposure in 0.1 –
early life.
 Development of allergic 0.0 –
disorders in children. Exposure to visible mould and/or
dampness during first 2 yrs of life

Meta-analysis of mould and dampness exposure on
asthma and allergy in eight European birth cohorts:
an ENRIECO initiative Tischer, Allergy 2011;66:1570

A moudly home OR for early asthma symptoms
enviroment in early life 0,3 –
is associated with an
 31 742 children from 8
increased risk of
ongoing European birth 0.2 –
asthma particulary in
cohorts.
young children and
 Reported mould or
allergic rhinitis 1.39
dampness exposure in
symptoms in 0.1 –
early life.
school-age children
 Development of allergic 0.0 –
disorders in children. Exposure to visible mould and/or
dampness during first 2 yrs of life

Lung function decline in relation to mould and
dampness in the home: the longitudinal European
Community Respiratory Health Survey ECRHS II
Norbäck Thorax 2011;66:396
% of houses with

 Participants in the 50 –
European Respiratory 50.1%
Health Survey initially
examined aged 20-45 yrs
40 –
41.3%
and 9 yrs later (n=6443). 30 –

 Dampness (water damage 20 –
or damp spots) and
indoor mould, ever and in 10 –
the last 12 months.
0
Any dampness Indoor mould

Additional decline in FEV1 ml/year
0
 Participants in the
European Respiratory -2.25
and 9 yrs later (n=6443). -5

 Dampness (water damage -7.43
or damp spots) and
indoor mould, ever and in
the last 12 months. -10
Women with In women with
dampness observed damp spots
at home in the bedroom

Additional decline in FEV1 ml/year
0
 Participants in the
Dampness and
Europeanmould growth
indoor Respiratory -2.25
is common in
dwellings, and the
andpresence of(n=6443).
9 yrs later damp -5
is a risk factor for
 Dampness (water damage
lung function decline,
-7.43
orespecially in women.
damp spots) and
indoor mould, ever and in
the last 12 months. -10
Women with In women with
dampness observed damp spots
at home in the bedroom


1) The additional mean lung function
decline, -2.25 ml/year for self-
reported dampness and -7.43 ml/year for
observed dampness in the bedroom, is of the same
order of magnitude as estimated for moderate
tobacco smoking in the same ECRHS cohort.

2) The reason for the sex difference in effect remains
unclear, but could be due to either higher susceptibility
or a longer exposure time in the dwelling for women.

School absenteeism among children living with smokers
Levy Pediatrics 2011;128:650
More days absent from school per
years than children living with 0
smokers in the home.

2 –
 Health and
absenteeism among
school children aged
1 –
1.54
6 to 11 yrs.
1.06
0
1 ≥2
Adults who smoked in
the home


Living with ≥2 adults who smoked
in the home OR for
3 –

 Health and
absenteeism among
2 – 2.65
6 to 11 yrs. 1 –
1.77
00
≥3 ear infections Having a chest
in the previous 12 cold in the 2
months weeks before
interview


Living with ≥2 adults who smoked
in the home OR for
3 –

Tobacco smoke
 Health and
exposure has
absenteeism among
significant
2 – 2.65
consequences for
6children and families
to 11 yrs. 1 –
1.77
above and beyond child
morbidity, including
academic disadvantage 00
and financial burden. ≥3 ear infections Having a chest
in the previous 12 cold in the 2
months weeks before
interview

Secondhand Smoke Exposure and Neurobehavioral
Disorders Among Children in the United States
Kabir, Pediatrics 2011;128:263

% children exposed to SHS
in the home
 Children ≤12 yrs 7 –
in the United States. 6 –

 Excess neurobehavioral 5 – 6%
disorders attributable to
4 –
secondhand smoke (SHS)
exposure in the home. 3 –

2 –

1 –

0

Kabir, Pediatrics 2011;128:263
PREVALENCE OF (exposed vs nonexposed)
20 –
18 –
16 –
14 – 15.1%
12 – 13.0%
10 –
08 – 8.7%
06 – 7.2%
04 – 5.5% 2.8%
02 –
0
LEARNING ATTENTION- BEHAVIORAL AND
DISABILITIES DEFICIT/HYPERACTIVITY CONDUCT
DISORDER DISORDERS

Children exposed to SHS at home had a
50% increased odds of2011;128:263
Kabir, Pediatrics having ≥2 childhood
neurobehavioral disorders
PREVALENCE OF (exposed vs nonexposed)
20 – compared with children who were
18 – not exposed to SHS.
16 –
14 – 15.1%
12 – 13.0%
10 –
08 – 8.7%
06 – 7.2%
04 – 5.5% 2.8%
02 –
0
LEARNING ATTENTION- BEHAVIORAL AND
DISABILITIES DEFICIT/HYPERACTIVITY CONDUCT
DISORDER DISORDERS

Parental Smoking and Vascular Damage
in Their 5-year-old Children
Geerts, Pediatrics 2012;129;45
Video still from the carotid
artery intima-media thickness
 Birth cohort. (CIMT) measurement.

 Smoking of parents during
pregnancy.
 259 participating children
5 years of age.
 Children‟s carotid artery
intima-media thickness
(CIMT) and arterial wall
distensibility were measured
by using ultrasonography.

Video still from the carotid
artery intima-media thickness
 Birth cohort. (CIMT) measurement.

pregnancy.
5 years of age.
 Children‟s carotid artery Diameter and intima-
intima-media thickness media thickness on the
(CIMT) and arterial wall far wall
is automatically
distensibility were measured detected
by using ultrasonography. and measured.


Children of mothers who had
 Birth cohort. smoked throughout pregnancy
had 18.8 µm thicker CIMT
(P=0.04) and 15% lower
pregnancy.
distensibility (P =0.02) after
 259 participating children adjustment for child‟s age,
5 years of age. maternal age, gender, and
breastfeeding.


Children of mothers who had
 Birth cohort. smoked throughout pregnancy
The associations had 18.8 µm thicker CIMT
were not found (P=0.04) and 15% lower
pregnancy.
in children of distensibility (P =0.02) after
mothers who had not
 259 participating children adjustment for child‟s age,
smoked of age.
5 years in pregnancy maternal age, gender, and
breastfeeding.
but had smoked
thereafter.


If both parents had smoked
 Birth cohort. during pregnancy,
with 27.7 mm thicker
CIMT (95%) and
pregnancy.
21% lower distensibility.
5 years of age.


Difference in CIMT (A) and distensibility (B) in children by
smoking habits of mother in pregnancy and current smoking


Dose of tobacco smoke exposure in pregnancy and difference
in CIMT (A) and distensibility (B) in the children


Paternal and maternal smoking during pregnancy
and vascular outcome in their children.

Parental Smoking and the Risk of Middle Ear Disease
in Children. Jones L, APAM 2012;166:18
OR for middle ear disease
in children
2 –

 Systematic review 1.62
and meta-analysis.
1 –
1.37
 Association between
secondhand tobacco
smoke and
middle ear disease 0
in children. maternal any household
member smoking
living with a smoker


Risk for surgery

2 –

1.86 1.83
 Systematic review
and meta-analysis.
1 –
secondhand tobacco
smoke and
middle ear disease 0
in children. maternal paternal



Risk for surgery

Exposure to 2 –
SHTS, particularly to
smoking by the 1.86 1.83
 Systematic review
mother, significantly
and meta-analysis. of
increases the risk 1 –
Middle Ear Disease
in childhood; this risk
secondhand tobacco
is particularly strong
smoke and requiring
for MED
middle ear disease
surgery 0
in children. maternal paternal


Secondhand Smoke Exposure in Cars Among Middle and
High School Students—United States, 2000–2009
King, Pediatrics 2012;129;446

% children exposed to
secondhand smoke in car
100 –

Students in grades 90 –
p<0.001
6 to 12. 80 –
82.3%
70 –
75.3%
60 –
Trends in 50 –
secondhand smoke 40 –

(SHS) exposure in 30 –

a car. 20 –
10 –
0
2000 2009

Secondhand Smoke Exposure in Cars Among Middle and
High School Students—United States, 2000–2009
King, Pediatrics 2012;129;446

% children exposed to
SHS exposure in cars secondhand smoke in car
100 –
decreased significantly
Students in grades
among US middle and 90 –
p<0.001
6 to 12.
high school students 80 –
82.3%
from 2000 to 2009. 70 –
75.3%
60 –
Nevertheless, in 2009,
Trends in 50 –
over 1/5 of
secondhand smoke 40 –
nonsmoking students
(SHS) exposure in 30 –

a car. exposed to
were 20 –
SHS in cars. 10 –
0
2000 2009

Exposure to parental and sibling smoking and the risk
of smoking uptake in childhood and adolescence:
a systematic review and meta-analysis
Leonardi-Bee Thorax 2011;66:847
OR of uptake of smoking in children
3 –

2.19
2 –
Meta-analyses 1.72
of 58 studies. 1.66

1 –
At least one Smoking Smoking

3 –
2.73
2.3
2 –
Meta-analyses
of 58 studies.

1 –
Both parents Smoking by


It is estimated that, 3 –
in England and Wales, 2.73
around 17000 young
people take up smoking
2.3
by the age of 15 each 2 –
Meta-analyses
year as a consequence
of 58of exposure
studies.
to household smoking.
1 –
Both parents Smoking by

Promoting Tobacco to Women of Reproductive Age
Harms Fetuses. Farber H, Chest 2012;141:839

 In utero tobacco smoke exposure has been repeatedly found to
be associated with increased risk for premature birth,
low birth weight, and sudden infant death syndrome.

 In utero tobacco smoke exposure only, in utero and postnatal
smoke exposure, and postnatal smoke exposure all associated
with increased risk of wheezing in the offspring compared with
those of nonsmoking mothers.


 Smoking cessation either before pregnancy or early in gestation
among women who are tobacco dependent can minimize the harm
to their offspring.

 Tobacco-dependence treatment medications are preferable to
continued in utero smoke exposure, which has well-defined harms
to the fetus.


to their offspring. and young women do not take up
When girls
smoking, their future offspring will be
protected from these harms.
continued in utero smoke exposure,tobacco-dependenceharms
When physicians offer which has well-defined
to the fetus.
treatment to women before they get
pregnant or early in their pregnancy,
harm can be reduced


to their offspring.

continued in utero smoke exposure, which has well-defined harms
to the fetus.

Reduction of smoking in women of
reproductive age needs to be a
public health priority.

Fetal Exposure to Maternal and Paternal Smoking and
the Risks of Wheezing in Preschool Children
Duijts L, Chest 2012;141:876

Background: Previous studies have suggested that
fetal smoke exposure is associated with increased risks of
wheezing during childhood.
We examined the associations of parental smoking during
pregnancy with wheezing in preschool children and whether
these associations are explained by postnatal smoke exposure
or small for gestational age at birth.

Fetal Exposure to Maternal and Paternal Smoking and
the Risks of Wheezing in Preschool Children
Duijts L, Chest 2012;141:876

OR for frequent wheezing at age
3 –
 Parental smoking
prospectively assessed
by questionnaires. 2 – 2.19
1 –
1.64 1.64
 Wheezing reported
at 1 to 4 years.
00
 4,574 subjects. age 1 age 2 age 3
In children exposed to continued
maternal smoking in pregnancy

What 2012 atopy risk protective factor

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What 2012 atopy risk protective factor