Tobacco Smoking andEnvironmental Risk Factors forChronic Obstructive PulmonaryDisease

Sundeep Salvi, MD, DNB, PhD

KEYWORDS

� Chronic obstructive pulmonary disease � Risk factors � Environmental � Tobacco smoking� Biomass smoke

KEY POINTS

� A better understanding of the risk factors associated with chronic obstructive pulmonary disease(COPD) is important to help prevent the development and progression of COPD.

� Tobacco smoking is an established risk factor for COPD. Tobacco can be smoked in different formsapart from cigarettes, many of which are more harmful. Exposure to second-hand smoke is also arisk factor for COPD.

� However, many other risk factors associated with COPD remain underappreciated or neglected.More than 50% of cases of COPD can be attributed to nonsmoking risk factors.

� Exposure to indoor air pollution resulting from the burning of biomass fuels is a major risk factor forCOPD, especially in developing countries.

� Other indoor air pollutants and outdoor air pollutants also contribute to the risk of COPD.

� Occupational causes contribute to up to 30% of COPD cases, but very little is known about this riskfactor. Farming is a neglected risk factor for COPD.

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INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is achronic progressivedisease of the airways and lungparenchyma that is associatedwith exposure to to-bacco smoke and other environmental insults ingenetically susceptible individuals. The damagedlungs in COPD are difficult to revert back to normal.Current management is therefore aimed atreducing the symptoms and rapid decline in lungfunction, and preventing acute exacerbations. Theeconomic burden associated with COPD is huge.Preventing the development of COPD, therefore,seems to be the only cost-effective public healthintervention strategy that can reduce the globalburden. Understanding the risk factors associatedwith the development of COPD is important so

Chest Research Foundation, Marigold Complex, KalyaninE-mail address: ssalvi@crfindia.com

Clin Chest Med 35 (2014) 17–27http://dx.doi.org/10.1016/j.ccm.2013.09.0110272-5231/14/$ – see front matter � 2014 Elsevier Inc. All

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that primary, secondary, and even tertiary preven-tive strategies can be developed.

The development of COPD is multifactorial, andthe risk factors include both genetic and environ-mental factors. The association between tobaccosmoking and chronic bronchitis was first high-lighted in 1955 by Oswald and Medvei.1 However,the landmark study that established the associa-tion between tobacco smoking and COPD wasthe 8-year prospective study of 792 British menby Feltcher and Peto,2 which observed that sus-ceptible smokers showed a sharp and progressivedecline in lung function that was the hallmark ofthis disease. The larger and longer Framinghamstudy from the United States has confirmed theseearlier reports.3 For the last 5 decades, tobaccosmoking has remained the most important risk

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factor associated with COPD across the world. Infact, the term COPD is used synonymously withsmoking-induced lung disease.As early as 1958, Fairbairn and Reid4 reported

that outdoor air pollution was an important riskfactor for COPD, and in 1963 Phillips5 reportedthat risk factors other than tobacco smokingwere associated with COPD. However, the over-whelming interest in smoking as the main risk fac-tor for COPD overshadowed these nonsmokingcauses. In 2003, Lundback and colleagues6 fromSweden and Mannino and colleagues7 from theUnited States reported that the population-attributable risk of tobacco smoking for COPDwas 45% and 44%, respectively, indicating thatmore than half of the cases of COPD were due tononsmoking causes. In the same year, Ezatti andLopez8 published global mortality rates attribut-able to smoking from all causes in The Lancet,and reported that 47% of COPD deaths in menand 78% of COPD deaths in women were notattributable to tobacco smoking (Fig. 1). In 2009,Salvi and Barnes9 reviewed the global literatureon the prevalence of COPD among never-smokers, and reported that between 25% and45% of patients with COPD across the globe hadnever smoked; highlighting the fact that COPD innever-smokers is much more common than waspreviously believed. A recent study on COPD prev-alence from 14 countries, defined by postbroncho-dilator spirometry values, reported that 23.3% ofthe COPD subjects were never-smokers.10

This article describes the role of tobacco smok-ing and the various environmental risk factorsassociated with the development of COPD. Otherrisk factors for COPD such as poorly treatedchronic severe asthma, status post pulmonarytuberculosis, poor socioeconomic status, andnutritional factors are not covered herein, and for

a discussion of these factors the reader is referredto the review by Salvi and Barnes.9

TOBACCO SMOKING

The cigarette looks deceptively simple, but it isone of the most effectively engineered inhaler de-vices that delivers a steady dose of nicotine to thehuman body. Nicotine is present in the tobaccoleaf, and its concentration varies depending onthe variety of tobacco leaf. For example, the brightvariety, which was originally grown in Virginia,United States, contains 2.5% to 3% nicotine,whereas the burley type of tobacco contains3.5% to 4% nicotine and the oriental tobaccotype contains less than 2% nicotine.Nicotine is an alkaloid that is an extremely

powerful drug. It stimulates the central nervoussystem and also increases the heart rate andblood pressure. Nicotine causes addiction similarto that of heroin and cocaine,11 and is containedin the moisture of the tobacco leaf. When the ciga-rette is lit it evaporates, attaching itself to minutedroplets in the tobacco smoke inhaled by thesmoker. After being deposited in the lung, nicotineis absorbed very quickly and reaches the brainwithin 10 to 19 seconds. The damage that occursin the lungs of tobacco smokers is mainly medi-ated by the tar present in the smoke, whereasthe nicotine is relatively harmless.Tar is the sticky brown substance that stains

smokers’ fingers and teeth yellow-brown. All ciga-rettes produce tar, but different brands producedifferent amounts. Earlier cigarettes (1950s) con-tained 30 mg tar per cigarette, but because ofstrict legislation modern cigarettes have tar levelslower than 11 mg per cigarette. According to theEuropean Union directives, upper limits of tar,nicotine, and carbon monoxide have been set at

Fig. 1. Global mortality attributableto smoking: 47% of male COPDdeaths and 78% of female COPDdeaths are not attributable to to-bacco smoking. (Data from Ezatti M,Lopez AD. Estimates of global mortal-ity attributable to smoking in 2000.Lancet 2003;362(9387):847–52.)

Smoking and Environmental Risk Factors for COPD 19

10 mg, 1 mg, and 10 mg, respectively. The type ofpaper used in the cigarette determines the amountof tar and nicotine that will be delivered into thelungs. Using more porous paper will let more airinto the cigarette, diluting the smoke and reducingthe amount of tar and nicotine entering into thelungs. Filters are made of cellulose acetate, andtrap some of the tar and smoke particles fromthe inhaled smoke. Filters also cool the smokeslightly, making it easier to breathe.

Apart from the dried tobacco leaf, the cigarettealso contains fillers made from the stems andother bits of tobacco, which are otherwise wasteproducts. These fillers are mixed with water andvarious flavorings and additives. Additives areused to make the tobacco products more accept-able to the smoker, and include humectants (mois-turizers) to prolong shelf life, and sugars to makethe smoke milder and easier to inhale. A total of600 such additives have been permitted by theDepartment of Health in the United States.Although many of these additives may seem quiteharmless on their own, they may be toxic in theircombination with other substances. Tobaccosmoke contains 4000 chemicals, at least 20 ofwhich are known to be carcinogenic.

Tobacco is inhaled in various other forms also.In India and other Asian countries, tobacco isrolled in dried tendu leaves (Diospyros melanoxy-lon), called bidi, and smoked (Fig. 2). Seventypercent of people in India smoke bidis mainlybecause they are cheap and easily available.Compared with cigarettes, bidis contain lesseramounts of nicotine (one-fourth of that in a ciga-rette) but produce 3 to 5 times the amount of tar,making it more harmful than cigarettes. Moreover,bidi smoking requires the person to smoke contin-uously and deeper to keep the bidi lit, which furtherincreases the tar deposition in the lungs. Otherforms of tobacco smoking include the hookah or

Fig. 2. Bidi: Tobacco wrapped in dried tendu leaf.(From Shutterstock, with permission. Available at:www.shutterstock.com.)

water-pipe and the chillum, which also containother additives apart from tobacco leaf. Theseforms of smoking have been shown to be moreharmful than cigarette smoke.12 Water-pipe smok-ing, which is common in the Middle East and Asia(Fig. 3), is perceived to be safer than cigarettesbecause the smoke passes through water, butstudies have shown that this smoke is as harmfulas cigarette smoke.13

Associations between tobacco smoking andCOPD have been shown in a large number ofstudies.14 It was earlier reported that 15% ofsmokers develop COPD, indicating a strong ge-netic basis, because a significant proportion ofsmokers do not develop COPD. However, Lund-back and colleagues6 have reported that up to50% of smokers can develop COPD, indicatingthat tobacco smoking poses a substantial risk forCOPD in the general population.

SECOND-HAND SMOKE OR ENVIRONMENTALTOBACCO SMOKE

The sidestream smoke from the burning ofcigarettes is called second-hand smoke or

Fig. 3. Water-pipe smoker or hookah. (From Shutter-stock, with permission. Available at: www.shutterstock.com.)

Fig. 4. Different types of biomass fuels (animal dung,wood, crop residues). (From Shutterstock, withpermission. Available at: www.shutterstock.com.)

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environmental tobacco smoke, which mainlycomes from the burning tip of the cigarette.Many toxins are present in higher concentrationsin the sidestream smoke than in the mainstreamsmoke.15 Typically, 85% of smoke in a room isdue to sidestream smoke. Woodruff and col-leagues16 and, more recently, Goldklang and col-leagues17 studied the mechanisms by whichsecond-hand smoke causes emphysema in ani-mal experiments. Apart from cellular and mediatorinflammation triggered by second-hand smoke,they report evidence of recruitment and activationof alveolar macrophages along with generation ofreactive oxygen species, which together triggerthe development of alveolar wall destruction.Exposure to second-hand smoke in human sub-jects has been shown to cause degradation ofbody elastin and possible injury to lung structure,thereby indicating a mechanism by whichsecond-hand smoke can lead to the developmentof emphysema.18

Earlier observational studies reported an associ-ation between exposure to second-hand tobaccosmoke and the risk of COPD.19–21 A case-controlstudy conducted by Kalandidi and colleagues19

reported that women married to smokers andexposed to 1 pack per day or less were at a2.5-times greater risk of having COPD than thosemarried to nonsmokers. Sandler and colleagues20

followed 14,783 healthy subjects exposed tosecond-hand smoke for 12 years and reportedthat the estimated relative risk of death fromCOPD was 5.65. Female spouses of smokersfrom Italy were reported to be at a 2.24-foldgreater risk of developing obstructive lung diseasethan those married to nonsmokers.21

A cross-sectional study from China reported anassociation between self-reported exposure topassive smoking at home and work and the riskof COPD.22 An average exposure of 40 hours perweek for more than 5 years was associated witha 48% increased odds of contracting COPD. Asimilar cross-sectional study from the UnitedStates involving 2113 adults between the ages of55 and 75 years reported that exposure tosecond-hand smoke was associated with a 36%greater odds of contracting COPD.23 Morerecently, a study from Taiwan reported thatwomen exposed to second-hand smoke had a3.65-fold greater risk of being diagnosed withCOPD, and that the duration of exposure tosecond-hand smoke correlated positively withthe severity of COPD. The population-attributablerisk for COPD from exposure to second-handsmoke was 47.3%.24 Because the prevalence ofcigarette smoking among Taiwanese men is high(55%–60%) and is low in women (3%–4%), a large

number of Taiwanese nonsmoking womenexposed to second-hand smoke seem to be at agreater risk of developing COPD. A recent pro-spective study conducted in 910 Chinese menand women for a period of 17 years reported thatexposure to second-hand tobacco smoke wasassociated with a dose-dependent and 2.3-foldgreater risk of COPD.25

However, not all studies have shown a positiveassociation between second-hand tobaccosmoke exposure and the risk of developingCOPD.26 More work needs to be done to studythe true impact of second-hand smoke on COPD.

EXPOSURE TO INDOOR BIOMASS FUELSMOKE

An estimated 50% of the world’s population and90% of the rural population of Africa and Asiause biomass fuels for cooking and heating pur-poses, accounting for more than 3 billion personsexposed to biomass smoke.27 Biomass fuelsinclude wood, animal dung, crop residues, driedtwigs, dried grass, and fossil coal (Fig. 4). Thesefuels are cheap and easily available in rural set-tings, and are therefore widely used by poor peo-ple. Even modern homes in many developedcountries are shifting their fuels from electricityand gas to biomass because of the increasingcost of cleaner fuels.28

Biomass fuels are inefficient because they notonly produce less heat but also burn incompletelyto release many noncombustible air pollutants.Crop residues are the least efficient, followed byanimal dung and wood. Burning of biomass fuelsproduces more than 200 known chemical com-pounds, more than 90% of which can penetratedeep into the lungs.29 These pollutants are classi-fied into gaseous pollutants (carbon monoxide,sulfur dioxide, nitrogen dioxide) and particulatepollutants (PM10 and PM2.5, which are particles

Fig. 5. A mosquito coil produces particulate matterequivalent to around 100 cigarettes. (From Shutter-stock, with permission. Available at: www.shutterstock.com.)

Smoking and Environmental Risk Factors for COPD 21

with a mass median aerodynamic diameter of10 mm and 2.5 mm, respectively). These tiny parti-cles are made up of black carbon, polyaromatichydrocarbons, chlorinated dioxins, arsenic, lead,and transition metals such as nickel and vana-dium. The indoor levels of PM10 in homes thatuse biomass fuel for cooking are often 5 to 50times above the safety limits prescribed by theWorld Health Organization.30 As many as 14 carci-nogenic compounds, 6 cilia-toxic compounds andmucus-coagulating agents, and 4 cocarcinogenicor cancer-promoting agents have been identifiedin biomass fuel smoke.31

Women are typically exposed to high levels ofbiomass smoke pollutants for between 3 and7 hours each day during cooking, often in poorlyventilated homes. On average, women spend60,000 hours during their lifetime cooking nearthe biomass stove, during which period they inhalemore than 25 million liters of highly polluted air.32

Two large meta-analyses investigated the asso-ciation between exposure to biomass smoke andthe risk of developing COPD. Hu and colleagues33

analyzed 15 published studies and concluded thatpeople exposed to biomass smoke had a 2.44-foldincreased risk of COPD compared with those notexposed. Po and colleagues34 analyzed 25studies, and also reported a 2.4-fold increasedodds of COPD amongwomen exposed to biomasssmoke. Of note, these odds are similar to thoseobserved in chronic smokers who developCOPD. Compared with 1.1 billion smokers world-wide, 3 billion people are exposed to biomasssmoke. It has therefore been argued that exposureto biomass smoke is probably a bigger risk factorfor COPD than tobacco smoking from a globalperspective.32 The association between exposureto biomass smoke andCOPD is seen in both devel-oping and developed countries. Sood and col-leagues28 reported that exposure to wood smokewas associated with a 70% greater prevalence ofCOPD in New Mexico County in the United States.The reader is referred to the article by Sood andcolleagues28 for more information on the impactof biomass smoke on COPD.

Preliminary work from the author’s laboratory in-dicates that subjects exposed to biomass smokewho develop COPD have a cellular and mediatorinflammatory profile in the airways similar to thatof tobacco smoke–induced COPD as evaluatedby induced sputum.35 Apart from greater small-airway obstruction in biomass smoke–inducedCOPD, the extent of physiologic impairment issimilar to that of tobacco smoke–inducedCOPD.36 More recently, the author compared thequality of life of patients with COPD caused bybiomass smoke exposure and those with tobacco

smoke–induced COPD using the St George ques-tionnaire, and observed that subjects with COPDfrom biomass smoke had the same degree ofimpairment in quality of life (unpublished observa-tions by the author, September 2013). Dutta andcolleagues37 have recently demonstrated thatbiomass users showed greater amounts of inflam-matory cells, cytokines (eg, interleukin-6, inter-leukin-8, tumor necrosis factor a), and oxidativestress in the induced sputum in comparison withwomen who use cleaner fuels.

Exposure to biomass smoke is now recog-nized as an important risk factor for COPD. Severalinterventional studies examining the impact ofimproved cooking stoves (reducing biomasssmoke) have reported improvements in lung func-tion, symptoms, and the prevalence of COPD.38–40

However, more work is needed to better under-stand the impact of different interventions thatreduce indoor biomass smoke on the burden ofCOPD.

OTHER INDOOR AIR POLLUTANTS

The other indoor air pollutant that could pose a sig-nificant risk for COPD in tropical countries is smokefrommosquito coils (Fig. 5). It has been shown thatburning one mosquito coil over a period of 8 hoursemits as much particulate matter and formalde-hyde as that equivalent to 100 cigarettes and 51cigarettes, respectively.41 Smoke from the burningof mosquito coils may therefore pose a significantrisk for the development of COPD, as these arewidely used in many African and Asian countriesto drive mosquitos away during sleeping hours.Moreover, mosquito-coil smoke has been shownto contain other harmful air pollutants, such as car-bon monoxide, isoprene and benzene, and heavy

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metals such as lead, nickel, chromium, and tin.Smoke from mosquito coils has been shown tobe a risk factor for lung cancer in Taiwan.42 Animalsexposed to mosquito-coil smoke have beenshown to have significant histopathologic changesin the lung, such as loss of cilia, emphysema,metaplasia of epithelial cells, and morphologic al-terations in alveolar macrophages.43 Despite theconcern over the risk of developing COPD frommosquito-coil smoke, very little research hasbeen done on this aspect, even in countries wherethe use of these coils is common.Other indoor air pollutants that are of poten-

tial risk in the development of COPD includecooking-oil smoke, kerosene smoke, incensesmoke, pesticides, and volatile organic com-pounds from furnishings. However, there is very lit-tle information on these pollutants as potential riskfactors for COPD.

OCCUPATIONAL COPD

Studies from developed countries indicate that thepopulation-attributable fraction for COPD associ-ated with occupational exposure varies between9% and 31%.44 A study from the United Statesestimated the population-attributable risk forCOPD due to occupation to be 43%.45 A prospec-tive cohort study among Swiss workers reportedthat the population-attributable risk of COPDwas 31% among smokers and 50% among non-smokers in workers exposed to biological dusts.46

The prevalence of occupational COPD is likely tobe greater in developing countries because ofthe lack of stringent regulations at workplacesand the lack of adequate protective gear.Several occupations are associated with an

increased risk for COPD, and these are listed inBox 1.

Box 1Occupations associated with COPD

� Dust exposures: coal mining, hard rock min-ing, concrete manufacturing, construction,tunneling, brick manufacturing, iron andsteel founding, gold mining

� Animal farming: organic dust, ammonia,hydrogen sulfide, bacteria

� Crop farming: organic and inorganic dust

� Chemical exposure: plastic, textiles, rubber in-dustry, leather manufacturing

� Diesel exhaust: trucking, transportation,automotive repair

� Road dust: sweeping

Farming

Farming is one of themost common and neglectedoccupations associated with an increased risk ofCOPD. Studies in crop farmers from Canada47,48

and the United States49 have reported higher prev-alence of chronic bronchitis and lower lung func-tion compared with controls. Lamprecht andcolleagues50 reported that 30.2% of the farmersin rural Austria showed evidence of poorly revers-ible mild airway obstruction and that 7.7% hadmoderate to severe COPD based on spirometry.Similar observations have been reported fromSpain,51 and more recently from the Philippines52

and China.53 In the Philippines, farming for morethan 40 years was found to be associated with a2.5-fold greater risk of COPD and was similar tothe risk associated with smoking tobacco formore than 20 pack-years.52 In China, the preva-lence of COPD was found to be 24.3%, 20.8%.17.9%, and 12.6% among fungus greenhousefarmers, poultry greenhouse farmers, flowergreenhouse farmers, and vegetable greenhousefarmers, respectively,53 although it is not knownwhether smoking was a major confounder in thisstudy.Several cross-sectional studies have shown that

animal farming is also associatedwith a greater riskof COPD. Poultry farming,54 pig farming,55 anddairy farming56 have been shown to be stronglyassociated with COPD. Poultry-farm workers(Fig. 6) are often exposed to total inhalable dustlevels exceeding 10 mg/m3 during most activ-ities.57 The composition of dust in animal farmsranges from wood dust to a complex mixture oforganic material derived from feed, litter, fecal ma-terial, dander, feather, andmicroorganisms. A Nor-wegian study reported that livestock farmers had a40% greater risk of COPD than crop farmers, andthis was strongly associated with ambient levelsof ammonia, hydrogen sulfide, and organicdusts.58 Farmers rearing more than one type oflivestock, for example, sheep, goats, and poultry,had a significantly higher risk of COPD than thoserearing only 1 type. Multiple etiologic factorsare linked to the risk of developing COPD at farmlocations, including organic dusts, endotoxins,peptidoglycans, and gases. Feeding operations insituations of large animal confinement also containa wide diversity of microbes such as gram-positivebacteria and archaebacteria.59 It has been sug-gested that chronic exposure to these inhalantshas a significant impact on local and systemicinflammatory responses that may underlie thedevelopment of chronic disease of the airways.60

Apart from organic dust, farmers are alsoexposed to significant amounts of inorganic soil

Fig. 6. Animal farming is an important occupationassociated with COPD. (From Shutterstock, withpermission. Available at: www.shutterstock.com.)

Smoking and Environmental Risk Factors for COPD 23

dust (Fig. 7). The highest dust exposures occurduring soil 5 preparation activities (eg, plowing,disking, and planting). Tractors pulling soil-preparation equipment generate large dust clouds,with particle concentrations reaching levels of upto 20 mg/m3, and sometimes even 100 mg/m3.61

Total respirable dust concentrations in tractorcans reach levels between 1 and 5 mg/m3. It has

Fig. 7. Dust exposure during farming, both organicand inorganic, is a risk factor associated with COPD.(From Shutterstock, with permission. Available at:www.shutterstock.com.)

been shown that respirable quartz exposures inagriculture commonly exceed industrial standards.Silicates are the predominant inorganic fractionfound in most soils, but in arid locations soil con-tent is dominated by calcium carbonate and othersoluble salts, whereas in warm humid climatessoil dust is made up of oxides and hydroxides ofiron and aluminum.62

Farming-induced COPD is poorly recognizedacross the world. Clinicians and policy makersneed to be made aware of this association, sothat early diagnosis and appropriate preventivestrategies can be instituted. Farming-inducedCOPD can be prevented by controlling harmfulexposures to organic dust, toxic gases, andchemicals on farms through improvements inanimal-rearing techniques, ventilation of animalaccommodation, careful drying and storage ofanimal feedstuffs, crops, and other products, anduse of personal protective equipment.63

Other Occupations Associated with COPD

Mining and quarrying were the first occupationsassociated with significant reductions in lung func-tion and the development of irreversible airflowobstruction. Coal mining has been shown to beassociated with the risk of developing emphy-sema, 6 times more so than in nonminers.64,65

Other mining activities that are generally charac-terized by silica exposure, such as gold, iron,and copper mining, and quarrying industriessuch as talc, potash, slate, and kaolin quarrying,have been reported to carry an increased risk ofCOPD.66

Petrochemical, mining, and steel industries areassociated with chronic exposures to metals thatare associated with an increased risk of COPD. ADanish study reported that cement and concreteworkers have a higher risk of being hospitalizedwith COPD in comparison with gainfully employedmen.67 Occupations associated with exposure todiesel exhaust, such as transportation, trucking,construction, and vehicle mechanics, have beenshown to be associated with an increased risk ofCOPD, but the evidence is weak.68

More recently, road sweepers from Pakistanhave been shown to have a higher prevalence ofCOPD, which was proportional to the duration ofexposure to road dust.69

In comparison with occupational asthma there isvery little literature on the management and pre-vention of occupational COPD, and there are nopublished guidelines. The diagnosis of occupa-tional COPD is infrequently made in clinical prac-tice, and the clinician must therefore be attentiveto all potential occupational causes in patients

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who have poorly reversible airway obstruction,especially among never-smokers.70 Effectivemanagement should necessarily focus on medicaltreatment of already prevalent COPD and efforts toprevent and/or limit ongoing further damage viareduction of exposure.70 The reader is referred toa review on this topic recently published in Clinicsin Chest Medicine.70

OUTDOOR AIR POLLUTION

Outdoor air pollution, mainly from motor vehicularand industrial emissions, has been shown to beassociated with various respiratory adverse ef-fects, especially lung development in childrenaged 10 to 18 years.71 The effects on adults arenot clear, but women seem to be more affectedthan men.72 In one of the largest published studieson the impact of traffic exposure on lung functionin the United States, heavier traffic density wasassociated with greater decrements in lung func-tion as evaluated by spirometry; when the distancefrom the main road was used as a parameter, thecloser was the residence from the main road, thelower was the lung function.72 Several biologicalmechanisms have been proposed to explain theharmful effects of ambient air pollutants, namely,increase in bronchial hyperresponsiveness, oxida-tive stress, airway inflammation, amplification ofviral infections, and damage to ciliary activity ofthe airways.73

Few studies have investigated the effects ofambient air pollution on the risk of COPD preva-lence. A German study of 4757 women living inthe Rhine-Ruhr Basin reported that ambientPM10 levels were significantly associated withthe risk of COPD. A 7-mg/m3 increase in 5-yearmeans of PM10 was associated with a 33%increased odds of contracting COPD. Moreover,women living within 100 m from the main roadhad 79% greater odds of presenting with COPDthan those who lived more than 100 m away.74

When the same cohort was followed up after10 years, the prevalence of COPD had reducedas the levels of PM10 reduced.75 A large cross-sectional study from Denmark showed a strongassociation between 35-year mean NO2 levelsand the risk of being hospitalized for COPD.76

A recent longitudinal cohort study from Vancou-ver, Canada, which examined the long-term expo-sure to elevated traffic-related air pollution with therisk of COPD hospitalization and mortality, re-ported that even a small increase in ambient blackcarbon air pollutants was associated with an in-crease in COPD hospitalizations and an increasein COPD mortality after adjustment for covari-ates.77 A study from Rome, Italy reported that

patients with COPD had 5 times greater mortalityassociated with ambient PM10 and NO2 levels incomparison with normal subjects. Moreover, pre-existing heart-conduction disorders and cerebro-vascular diseases were found to have strongereffects in older men with COPD.78

Despite all the evidence, it remains unclearwhether ambient air pollution may lead to a declinein lung function and subsequent development ofCOPD. Because few studies have confirmedCOPD by spirometry and the published data areconflicting, a causal relationship between outdoorair pollution and COPD cannot be drawn at thisstage.73 A study from Nottingham, UnitedKingdom did not report any association betweenambient levels of air pollutants and COPD.79 Arecent meta-analysis of 8 morbidity and 6 mortalitystudies reported that the evidence of chroniceffects of air pollution on the prevalence and inci-dence of COPD among adults was suggestive butnot conclusive, despite plausible biological mech-anisms and good evidence that air pollutionaffects lung development in childhood and triggersexacerbations in COPD patients. The investigatorsrecommend that larger studies with longer follow-up periods, specific definitions of COPD pheno-types, and more refined and source-specificexposure assessments are needed before anyconclusive statement can be made.80

SUMMARY

Tobacco smoking is an important and preventablerisk factor for the development and progression ofCOPD. Apart from the cigarette, several otherdevices are used to inhale tobacco smoke, manyof which are in fact more harmful than cigarettes.However, tobacco smoking is not the only riskfactor associated with COPD. Second-hand expo-sure to tobacco smoke has also been shown to beassociated with the risk of COPD, although morerobust evidence needs to be generated. Exposureto biomass smoke occurs in 50% of the world’spopulation, especially in Africa and Asia, and is amajor risk factor for COPD that is often neglected.Other indoor air pollutants are also important.Occupational causes contribute to up to 30% ofCOPD, and several occupations are associatedwith a greater risk of developing COPD. Farmingis an important and neglected occupation associ-ated with COPD. Cross-sectional studies haveshown as association between outdoor air pollu-tion and COPD, but more robust evidence isrequired.A better understanding of the risk factors and

their relative contribution to the development ofCOPD will help guide policy makers and health

Smoking and Environmental Risk Factors for COPD 25

care providers to take appropriate interventionalmeasures for primary as well as secondary pre-vention. Only then will the global burden ofCOPD be reduced.

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