Conflict of interest

Bilimsel Danışma Kurulu, Kongre/toplantı sponsorluğu, konuşmacı veya bilimsel araştırma desteği sağlanan kuruluşlar(Harf sırasına göre sıralanmışlardır)

AstraZenecaBoehringer-Ingelheim

ChiesiGSK

NovartisNycomedTÜBİTAK

Conflict of interest

Nonsmoking risk factors in COPDEnvironmental and occupational exposure

Dr. Mehmet Polatlı

Smoking is the most important risk factor in COPD. But not the only one.

COPD due to smoking “Population attributable fraction,PAF” is usually < % 80

COPD prevalance in never smokers % 3-15 (BOLD, PLATINO)

PAF is lower in young adults, women and lower developed economics

OTHER RISK FACTORS?

RISK FACTORS EXCEPT SMOKING

Genetics Chronic asthma Air pollution and passive smoking Occupational exposure Biomass Diet

Factors effecting lung function and COPD development

Speizer and Tager

Cellular inflammation in COPD

Lung and ambient air 400 L oxygen/day 10.000 L air inhalation/day İndoor and outdoor air pollution

Primary pollutants: SO2, NO2, CO, CO2, UOB, PM, NH3, Pb, etc

Secondary pollutants: Ozon (O3) ve NO2 Particulate matter (PM) suspended particles in the air

(diesel exhaust, energy sources)▪ < 10 µm PM10 2.5-10 µm course PM; ▪ <2.5 µm PM2.5 fine PM; < 100nm ultrafine PM

Proposed levels of pollutants for clean air

150 400 100 300 150 300 240Türkiye Hava Kalitesinin korunması yönetmeliği 1986

Increased populationUrbanizationIndustrilizationVarious consumptionConsumption fossil fuelVehicle trafficTopographic characteristics of the

landGeografical reasons

Ambient air pollution factors

Acute effects of air polllution

Increase in symptoms Decrease in lung function Increase in seeking medical advice Increase in emergency consult Hastaneye admission Mortality

Sunyer J, Eur Respir J 2001, Review conclusion

The effects of ambient air pollution on inflammation Increase in ROS and inflammation Direct toxic effects of the particulates İnflux of inflammatory cells in the airways Macrophages stimulation Intertitial stimulation Decrease in mucociliary clearance Increase in epitelial permeability Pulmonary vasculature

MacNee, Donaldson, Review in Eur Respir J, 2002 Ling SH el al. International Journal of COPD 2009:4

Is there chronic effects of air pollution?

When do the effects of the polutants begin?

How do the symptoms and pulmonary function change?

Does it effect on PFT after going away from the pollution area ?

Does the mortality increase?

The factors effecting lung function and development

Speizer and Tager

Air pollution and COPDSunyer J. ERJ 2001

Air pollution and COPD Sunyer J. ERJ 2001 …conclusion

CB and emphysema increase in NHANES and AHSMOG studies

Dyspnea and mucus hypersecretion in SAPALDIA

Lower PFT values in cross-sectional studies

air pollution is related to an increased prevalance in COPD.

The effects of air pollution begins antenatal period

Latzin P et al. Air pollution during pregnancy and lung function in newborns: a birth cohort study. ERJ 2009

The effects of air pollution begins antenatal period

> 200 chemical and pollutants’ presence in umblical cord suggests that placenta is not have a role in barrier agaşnst these substances

Low birth weight,, preterms and increased perinatal mortality

Sudden baby death syndrome commonLatzin P et al. ERJ 2009

Neonatal and childhood period

Neonatal period significant association between O3, CO, SO2, NO2 and respiratory problems

The most significant association is between NO2 and O3

Lung Function Growth in Children with Long-Term Exposure to Air Pollutants in Mexico City. AJRCCM 2007

3170 children, 3 years follow, 7 PFT measurement

Deficits in FVC and FEV1 growth over the 3-year follow-up period were significantly associated with exposure to O3, PM10

and NO2 increase in mean O3 concentration

was associated with an annual deficit in FEV1 of 12 ml in girls and 4 ml in boys

Chronic bronchitis symptoms are associated with COPD risk

11 years follow up Aged: 18-60 years COPD OR 1.23 after adjusted for age, sex,

education, smoking, asthma, wheezing

Probst-Hensch N et al. Swiss SAPALDIA Study, Thorax 2010;65:150-156

Asthma, CB and emphysema in the parents increase the effects of air pollution

20 years follow up in nonsmokers. PM, Sulfates, SO2 and O3 effects on PFT.

1391 nonsmokers. In case of asthma, bronchitis and empysema

history in family PM10>100g/m3 increase (54 days/year) FEV1

decrease associate with % 7.2 Mean 8 hours O3 23 ppb increase FEV1 decrease

% 6.3 Males SO4 density 1.6g/m3 increase FEV1 decrease

% 1.5 AM J RESPIR CRIT CARE MED 1998;158:289–298.

Improvements in PM10 Exposure and Reduced Rates of Respiratory Symptoms in a Cohort of Swiss Adults (SAPALDIA)

SAPALDIA 1991, 9651 adults SAPALDIA 2002, 7019/8047 adults PM10 decrease effect on symptoms. PM10 mean decrease level 6.2 µg/m3 Improvements in PM10 Exposure Reduced Rates

of Respiratory Symptoms in a Cohort of Swiss Adults

▪ Schindler et al. 179 (7): 579. (2009)

Respiratory Research 2005, 6:152

Seventh Day Adventist StudyAbbey DE et al. Environmental Health Perspectives

6102 adults follow up; obstructive airway disease and doctor diagnosed COPD

obstructive airway disease and chronic bronchitis total particulates >200 µg/m3 and exposure duration>1000 hours/year risk 1.36 ve 1.33.

European Prospective Study into Cancer and Nutrition (EPIC) Study

EPIC, 3904 adults in Atina 168 healthy control (mean FEV1/FVC:% 102) 168 COPD symptomatology(+) PFT and

examination 84 CB, empysema or COPD KOAH NO2 and black smoke index in the last 5 years Eposure ¼ increase, disease risk increase % 37

When most of the subjects exposed are

considered vs. all others, there is a twofold increase in disease risk

Karakatsani et al. J Epidemiol 2003;18(1):45-53

Naess et al . Relation between Concentration of Air Pollution and Cause-Specific Mortality: Four-Year Exposures to Nitrogen Dioxide and Particulate Matter Pollutants in 470 Neighborhoods in Oslo, Norway. Am J Epi 2007 143.842 aduts; 51-70 ve

70-90 years NO, PM10, PM2.5 effects Air pollution associated

with mortality NO2 > 40g/m3 significant chronic obstructive

pulmonary disease and the elderly seem to be susceptible to air pollution at lower levels than the general population

persons discharged alive with chronic obstructive pulmonary disease

PM10’da 10µg/m3 increase mortality % 22

Environmental Health 2008, 7:48

Strong evidence of association outdoor pollution and decreased lung growth in adolescence and childhood

Few study with spirometry but suggestive evidence with air pollution and COPD

The likelihood of the role of air pollution with COPD is high because of PFT results

PM ve FEV1, COPD

Sean H Ling, Stephan F van Eeden. International J COPD 2009.

PM ve COPD PM inhaled from cigarette smoke or ambient air

pollution particles from other sources both have been associated with the development and progressionof COPD

With the rapid urbanization of the population, a better understanding of the importance is necessary for educational and preventative measuresSean H Ling, Stephan F van Eeden. International J COPD 2009.

Environmental tobacco smoke

Ventilation decreases the cigarette smoke indoors but doesn’t decrease health risks

TC Sağlık Bakanlığı. Türkiye Kronik Hava Yolu Hastalıklarını Önleme ve Kontrol Programı.Kasım 2010

Environmental tobacco smoke and CB (SAPALDIA) ETS (+) and (-) 4.197 nonsmoker (18-60 yaş) Cross-sectional analysis

CB OR 1.65 (1.26-2.14) Dispnea OR 1.43 (1.18-1.74)

Leuenberger et al. AJRCCM 1994

Environmental tobacco smoke and COPD 2.113 adults , 55-75 aged; telephoned

ETS history Prenatal, home and work place Doctor diagnosed CB, Empysema, COPD

OR 1.55 (CI 1.09-2.21) PAF home ETS % 11, work % 7

public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure.Eisner MD et al. Environmental Health: A Global Access Science Source 2005, 4:7

Passive smoking exposure and risk of COPD among adults in China

Yin et al. Passive smoking exposure and risk of COPD among adults in China: the Guangzhou Biobank Cohort Study.Lancet 2007; 370: 751–57.

ETS and COPD risk

Exposure level ETS in home and work

Outcomes Chronic respiratory symptoms COPD (FEV1/FVC < % 70)

Exposure densitySmokers in homeSmokers in work

Exposure duration

Hours/weekExposure

duration (yıl)

Exposure burdenLow<2 yıl;40

s/hfMod 2-5 yıl; 40

s/hfHigh>5 yıl; 40

s/hf

Yin et al. Passive smoking exposure and risk of COPD among adults in China: the Guangzhou Biobank Cohort Study.Lancet 2007; 370: 751–57.

ETS and COPD

Yin et al. Passive smoking exposure and risk of COPD among adults in China: the Guangzhou Biobank Cohort Study.Lancet 2007; 370: 751–57.

ETS and Symptoms

Lancet 2007; 370: 751–57

ATS statementETS and COPD

American Thoracic Society Documents: An Official American Thoracic Society Public Policy Statement: Novel Risk Factors and the Global Burden of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med Vol 182. pp 693–718, 2010

ETS and COPD in Sivas

74 COPD females and 74 healthy controles Biomass > 30 years OR 6.61 (%95 CI 2.17-

20.18) ETS> 30 years OR 4.96 (% 95 CI 1.65-

14.86)

ETS in South East Turkey

> 40 years of age males, 63/348 COPD (% 18.1)

Cafe for regularly OR 5.37 Cafe visit/week OR 2.72 Cafe visit/month OR 2.33

Turk J Med Sci 2010; 40 (3): 349-355

PAR %11

PAR % 7

Environmental Tobacco Exposure Are Enhanced by Bronchial Hyperreactivity(SAPALDIA 1991-2002)

Am J Respir Crit Care Med Vol 174. pp 1125–1131, 2006

Occupational dust and chemicals

Organic and inorganic dusts and chemicals, gases

Some agents in experimental studies CBendotoxin, mineral dust, SO2, vanadium) emphysema Kadmium, coal, endotoxin, silica

An Official American Thoracic Society Public Policy Statement: Novel Risk Factors and the Global Burden of Chronic Obstructive Pulmonary Disease 2010

Multifactorial (host, others) Differantiation is difficult from the disease

caused by other agents Most workers are smokers and/or irritants in work Healthy workers effect Follow up difficulties after leaving work There is no subgroup like occupational asthma.

Chronic, slow progression Irreversibl after leaving work

Difficulties in the assessment occupational and COPD association

Kuempel ED et al. Contributions of Dust Exposure and Cigarette Smoking to Emphysema Severity in Coal Miners in the United States. AJRCCM 2009

Sigara içmeyen grup Sigara içen grup

Kauffmann, F. J Epidemiol 1979

Additif effects

Only occupational exposure OR 1.4 Only smoking OR 2.8 Smoking and occupational exposure

OR 6.2

▪ Trupin et al. ERJ 2003

median PAR % 19

median PAR % 15

KOAH Median PAR % 15

Occupational exposure and PAF

ATS statement 2010: median PAF % 15-20

GOLD 2009 Hnizdo 2002, NHANES III Study Occupational PAF % 19.2 but in nosmokers % 31.1.

Conclusion Classical example for interactive relation

of gene and environment.Toxic gasses and particules effect the lung additively.

Defining risk factors other than smoking and taking measures is important

ETS and ambient air pollution contribute COPD.

Occupational exposure should be taken into account.