I fattori ambientali
nell’iperreattività
bronchiale
Luciana Indinnimeo
Dipartimento di Pediatria e NPI
1
ESPOSIZIONE: contatto degli inquinanti ambientali con il
sistema respiratorio.
E’ determinata da due parametri fondamentali:
concentrazione degli inquinanti
durata dell’esposizione
Dalla seconda metà degli anni 1980 numerosi studi hanno
valutato gli effetti dell’ inquinamento sulla salute respiratoria.
Principali fattori di rischio ambientali
Epidemiol Prev 2009; 33(6) suppl 2: 1-72
Marion Hulin Eur Respir J 2012; 40: 1033-1045
WHO air quality guideline (AQG)
WHO last revised its AQG values for PM in 2005, as follows:
PM2.5: 10 μg/m³ for the annual average
25 μg/m³ for the 24-hour mean (not to be exceeded for
more than 3 days/year);
PM10: 20 μg/m³ for the annual average
50 μg/m³ for the 24-hour mean.
Exposure to air pollution (particulate matter) in outdoor air.
Copenhagen, WHO Regional Office for Europe, 2011 (ENHIS Factsheet 3.3)
(http://www.euro.who.int/__data/assets/pdf_file/0018/97002/ENHIS_Factsheet_3.3_July
_2011.pdf, accessed 28 October 2012).
Exposure to air pollution (particulate matter) in outdoor air.
Copenhagen, WHO Regional Office for Europe, 2011 (ENHIS Factsheet 3.3)
(http://www.euro.who.int/__data/assets/pdf_file/0018/97002/ENHIS_Factsheet_3.3_July
_2011.pdf, accessed 28 October 2012).
Meccanismi?
• airway inflammation (O3,NO2,PM <2,5 μm)
• airway hyper-responsiveness (O3,NO2)
• oxidative stress (O3,NO2,PM <2,5 μm)
21/12/2015
Mechanistic framework for air pollution effects in asthma
increased deposition of allergen in the airways due to carriage by particles
increased epithelial permeability due to oxidative injury,
increased antigenicity of proteins from chemical modification,
Suppression of Treg function: epigenetic mechanism, hypermethylation of
CpG islands in Foxp3 (Nadeau K.2010, Brunst KJ.2013)
Allergic inflammation with Th2 and Th17 phenotypic differentiation (van Voorhis M. 2013)
Guarnieri M. Lancet 2014
During childhood, urban air pollution has been associated with:
respiratory symptoms
changes in lung function
respiratory tract infections
croup
persistent cough
healthcare use
Fattori ambientali outdoor
11
• 214 children
• personal prenatal PM2.5 exposure
• occurrence of acute bronchitis and pneumonia diagnosed by a physician
from birth over the seven-year follow-up
• incidence of recurrent broncho-pulmonary infections (five or more spells
of bronchitis and/or pneumonia) in the follow-up significantly correlated
in a dose-response manner with the prenatal PM2.5 level
(OR = 2.44, 95%CI: 1.12–5.36).
Predicted probability of recurrent broncho-pulmonary infections (five or
more episodes treated by physician in the follow-up) related to prenatal
exposure (ln-transformed PM2.5 μg/m 3 ).
Wiesław A. Jedrychowski , International Journal of Hygiene and Environmental Health, Volume 216, Issue 4, 2013, 395 - 401
January 2014 Pediatric Pulmonology
• 1.263 mother-child pairs enrolled during the first trimester of
pregnancy in Project Viva during 1999–2002.
• distance from home to nearest major roadway and traffic
density in a 100m buffer around the home were calculated.
• doctor-diagnosed pneumonia, bronchiolitis, croup, or other
respiratory infection from birth until the early childhood visit
(median age 3.3).
Distance to Major Roadway at Enrollment Home Address
Distance to major roadway and relative risk of respiratory
symptoms
Am J Respir Crit Care Med Vol 187, Iss. 12, pp 1341–1348, Jun 15, 2013
birth cohort of 366 infants of unselected mothers,
respiratory health was assessed weekly by telephone interviews
during the first year of life
daily mean levels of PM10, NO2 and O3 were obtained from
local monitoring stations
significant association between air pollution and respiratory
symptoms (risk ratio, 1.13 [1.02–1.24] per 10 mcg/m3 PM10 levels)
during times of elevated PM10 (>33.3 mcg/m3), duration of
respiratory tract infections increased by 20%.
Air pollution concentrations, mean respiratory symptom scores, and mean
respiratory tract infections
Laura Perez, et al. Am J Public Health. 2009;99:S622–S628.
burden of childhood asthma associated with air pollution in the
southern California communities of Long Beach and Riverside.
reductions in traffic-related nitrogen dioxide and ozone would
reduce bronchitic episodes in asthmatics by 36–70%.
Am J Respir Crit Care Med Vol 186, Iss. 12, pp 1286–1291, Dec 15, 2012
1,900 children in the Swedish birth cohort were followed with
questionnaires, spirometry, and IgE measurements until 8 years
of age
Outdoor concentrations of particulate PM10 from road traffic
were estimated
Early life exposure to traffic related air pollution seems to have
long-term respiratory consequences in susceptible groups,
such as children with atopy.
Exposure during the first year of life
was associated with a reduced FEV1
at 8 years of age.
The negative association was
particularly pronounced in children
concomitantly sensitized to common
inhalant or food allergens
Lung function measurements in relation to traffic PM10 exposure
during different time periods of life:
black, first year of life exposure;
white, first to fourth year exposure;
gray, fourth to eighth year exposure
Environmental Health Perspectives • volume 122-number 1-January 2014
Conclusion
Our meta-analysis of 10 European birth cohorts (N-Total = 16.059)
within the The European Study of Cohorts for Air Pollution Effects
(ESCAPE 2009) project found consistent evidence for an
association between air pollution and pneumonia in early
childhood.
NO2
PM2.5
Traffic intensity on nearest street
PM10
Fattori ambientali indoor
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The mean indoor PM2.5 and PM10 concentrations were
39.5±34.5 μg/m3 and 56.2±44.8 μg/m3, compared to the
ambient PM2.5 and PM10 (15.6±6.9 and 21.8±9.53 μg/m3, respectively).
Common household activities, especially smoking and sweeping,
contributed significantly to higher indoor PM.
Indoor PM Concentrations in Inner-City Baltimore Homes.
In-home PM concentrations were significantly higher than ambient PM concentrations
(p<0.01).
Over 75% of homes exceeded the Environmental Protection Agency (EPA) annual limit
for ambient PM2.5 , 47% of homes exceeded the annual limit for PM10.
Open windows were associated with significantly lower indoor PM
Il PM è significativamente associato a sintomi
respiratori e all’uso di farmaci al bisogno
McCormack MC, et al. Environ Health Perspect 117:294–298 (2009)
EHP 2008;116:1428–1432.
150 bambini(2–6 anni) con asma diagnosticata dal
medico
Concentrazione media di NO2 in casa:
30.0 ± 33.7 ppb.
La maggiore concentrazione di
NO2 indoor è significativamente
associata all’aumento dei sintomi
respiratori in bambini asmatici di
età prescolare.
Study on Health Effects of School Environment (HESE)
PM10
Standard by
US-EPA (24hr)
Standard by
US-EPA (annual)
Schoolchildren exposed to PM10 >50 µg/m³ were 78%
CO₂
Schoolchildren exposed CO2 >1.000 ppm were 66%,
Ventilation rate
A poor ventilation rate was significantly more frequent in naturally
ventilated classrooms (67%) than in those with mechanical ventilation
(97% versus 13%, p=0.001).
APRIRE LE FINESTRE!!!
Prevalence of recent respiratory disorders by indoor exposure level of
PM10 and CO2,
associations of respiratory disorders with exposure levels
Current asthma and respiratory symptoms among pupils in
Shanghai, China: influence of building ventilation, nitrogen
dioxide, ozone, and formaldehyde in classrooms.
1414 pupils: 8.9% had doctors' diagnosed asthma, 3.1% wheeze,
23.0% daytime breathlessness, 2.4% current asthma, and 2.3% asthma medication
OR
CO2
NO2
p
Current asthma
1.18
< 0.01
Asthma medications
1.15
< 0.05
Current asthma
1.51
< 0.01
1.45
< 0.01
Asthma medications
Multiple logistic regression model
Mi YH et al.,Indoor Air 2006 Dec;16(6):454-64.
401 randomly chosen classrooms in 108 primary schools attended by
6590 children (mean age 10.4 years) in the French 6 Cities Study
An increased prevalence of past year asthma was found in the classrooms with
high levels of NO2, PM2.5 and acrolein.
Am J Respir Crit Care Med 2006; Vol 173: 1255–1263
The impact of pre- and postnatal passive smoking on respiratory functions
20.000 children (aged 6–12 yr) from 9 countries in Europe and North
America
Smoking during pregnancy, 19.7%
Smoking exposure during first 2 yr, 54.3%
Current ETS exposure, 55,6%
Effect estimates of smoking during pregnancy
Am: North America
De: Germania
Nl: Olanda
Pl: Polonia
Hu: Ungheria
Cz: Repubblica Ceca
Sk: Slovenia
Moshammer et al,
Am J Respir Crit Care Med 2006
Public Health Reports / May–June 2010; 125: 478-487
In Europe, exposure to environmental tobacco smoke (ETS) caused an
estimated 24% to 32% of sudden infant death syndrome cases and
increased the number of asthma episodes by 7% to 11% in children
younger than 14 years of age.
The major source of exposure to ETS among children is
smoking by parents and other household members.
IL FUMO DI “TERZA MANO”
è l’involontaria esposizione (inalazione,
ingestione o assorbimento dermico) a residui
della combustione del tabacco che
• rimangono sulle superfici, nella polvere e
sui vestiti
• vengono ri-emessi in fase gassosa
• reagiscono nell’ambiente con ossidanti e
formano inquinanti (nitrosamine-cancerogene)
Winckoff Pediatrics 2009
Matt et al Envir Health Persp 2011
 Strategie volte a ridurre l’esposizione ad inquinanti indoor:
- curare l’igiene domestica,
- allontanare il bambino durante le pulizie di casa,
- rimuovere le sorgenti di VOC e formaldeide
- migliorare la ventilazione (compresa l’apertura delle finestre),
- adeguata manutenzione delle caldaie,
- mantenere l’umidità relativa tra 45–50%,
- utilizzare aspirapolvere con filtri HEPA,
- evitare l’uso di umidificatori,
- divieto assoluto di fumo in casa.
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Centro Nazionale per la Prevenzione ed il Controllo delle Malattie
Progetti CCM 2010
PROGETTO
Esposizione ad inquinanti indoor:
linee guida per la valutazione dei fattori di rischio
in ambiente scolastico e definizione
delle misure per la tutela della salute respiratoria degli
scolari e degli adolescenti (Indoor-School)