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© 2007 The Union

Historical statistics support a hypothesis linking

tuberculosis and air pollution caused by coal

G. A. Tremblay
Phoresia Biotechnology Inc., Laval, Québec, Canada


Tuberculosis (TB) is generally considered to be linked to TB disease in Canada, USA and China are correlated.
industrialisation and urbanisation. Peaking in the 1800s A hypothesis linking TB and air pollution is developed
and receding slowly after, the disease declined sharply in in the context of industrialisation. A model is proposed
the West after World War II. TB has made a comeback in whereby triggering of the interleukin-10 (IL-10) cascade
the last 20 years in developing countries such as China by carbon monoxide in lung macrophages promotes the
and India. Because socio-economic conditions alone can- reactivation of Mycobacterium tuberculosis.
not explain the connection between industrialisation and K E Y W O R D S : tuberculosis; coal; air pollution; carbon
TB, factors remain to be determined in the aetiology of monoxide; IL-10
the disease. Historical statistics on coal consumption and

THE INVENTION of the blast furnace and the steam ditions. Improvements in living conditions are there-
engine were key developments that led to industriali- fore likely to affect TB incidence.
sation. From that point on, fossil fuel has driven the There is general agreement that the TB epidemic
evolution of the world as we know it today; with increased dramatically in Europe in the eighteenth
progress and technical innovations, changes in life- and nineteenth centuries and began to decline there-
style ensued promptly. However, as humans unlocked after.3 TB is intrinsically linked to industrialisation.
their creative potential in mechanics, they may also For example, both industrialisation and TB occurred
have unleashed the avatar of progress. later in Japan.4 As there is no obvious reason to be-
A century-old belief blamed foul air or miasmas lieve that there was less poverty before industrialisa-
for diseases such as tuberculosis (TB), malaria, rheu- tion, and considering that overcrowding is relevant to
matism and cholera. A number of scientists, including all communicable diseases, one is forced to question
Florence Nightingale and William Farr, supported the why industrialisation and TB go together.
theory. Nevertheless, miasmas fell into disgrace when Another unresolved issue concerns the decline of
Louis Pasteur discarded spontaneous generation and TB in the West. For example, between 1850 and 1910,
it became clear that micro-organisms were largely re- TB death rates declined in England and Wales much
sponsible for mankind’s ills. faster than indicators of social deprivation.5 It seems
Mycobacterium tuberculosis, the agent responsible therefore that social factors alone cannot explain the
for TB—also called phthisis or consumption—was decline in TB incidence.
identified in 1882 by the German physician Robert There may in fact have been some degree of confu-
Koch. At the time, TB claimed about one death in six sion between social and environmental factors. For
in Europe. example, in a 1911 study,6 Marie-Davy compared TB
TB has made a comeback in the last 20 years, mostly mortality and the average number of windows per
in parts of the developing world. In 2004, 9 million household (Figure 1) in Paris arrondissements (urban
new TB cases were diagnosed and approximately 2 districts) between 1858 and 1902. Scientists of the
million persons died of TB around the world. More time were aware that inadequate aeration of houses
than 80% of all TB patients live in sub-Saharan Africa was related to the development of TB in residents;
and Asia. People infected with the human immunode- Figure 1 may also indicate high levels of indoor air
ficiency virus (HIV) are more susceptible to TB.1 In Af- pollution in urban households.
rica, for example, HIV is said to drive the TB epidemic.2 In recent years, air pollution has been identified as
TB has been termed a ‘social disease’ because it is a risk factor for TB. Mishra et al. linked biomass
linked to poverty, overcrowding and unsanitary con- cooking fuels and TB:7 based on a 1992–1993 survey

Correspondence to: Guy A Tremblay, 3126, 5ième Rue, Laval, Québec H7V 1M1, Canada. Tel: (1) 514 436 9272. e-mail:
Article submitted 24 September 2006. Final version accepted 26 January 2007.
Air pollution caused by coal impacts on tuberculosis 723

cascade is discussed. The observations shed new light

on TB biology and epidemiology and emphasise the
importance of environmental health.

Historical statistics of disease in Canada, as incidence
per 100 000 population, are gathered from Statistics
Canada Historical Statistics on ‘Annual rates of notifi-
able diseases, Canada, 1926 to 1975’ (series B517–
525).12 For electricity production, ‘Electric utilities—
number of customers by class, 1920 to 1975’ (series
Q97–101) is used.12 Electricity production is ex-
Figure 1 TB mortality rate as related to the average number of pressed as percentage of maximum customers over the
windows per household in Paris urban districts or arrondisse- period interval. ‘Principal statistics of the Canadian coal
ments between 1858 and 1902. pop  population. mining industry, 1918 to 1976’ (series Q137–142) is
used for the numbers of employees in the coal indus-
try.12 Number of coal employees is expressed as per-
on 90 000 households, the study provides evidence centage of maximum over the period. Bacille Calmette-
that women in biomass-using households are three Guérin (BCG) vaccination in Canada, expressed as total
times more likely to report TB than those in households number of vaccine shots, was compiled by Malissard.13
using cleaner fuels. Another Indian study found that US Department of Energy Official Energy Statistics
households using wood or dung cakes as fuel had 2.5 provides historical statistics on coal consumption by
times more clinically confirmed TB.8 Cigarette smoking sector in million short tons from 1949 to 2005,14 and
is now recognised as a risk factor for TB infection.9 the Centers for Disease Control and Prevention (CDC)
Miners in coal and gold mines are also prone to TB, al- Division on Tuberculosis Elimination Statistics data
though it is considered an effect of silicosis.10,11 on historical TB in the US (incidence/100 000 between
Based on the observation that industrialisation and 1953 and 2005).15
TB coincide, and on the assumption that a determi- Data on coal consumption (exajoules) in China are
nant factor remains to be identified in the TB epi- taken from the China Statistical Yearbook 2003,16
demic, historical statistics of disease and energy were and TB notification rate (/100 000) from the WHO TB
compared to assess the impact of environmental fac- report 2005.17 The poverty headcount index repre-
tors on TB. sents the percentage of the population living in house-
The present hypothesis suggests that pollution holds with income per person below the poverty line.
caused by combustion of coal and possibly town gas The headcount index is provided by the World Bank
during industrialisation aggravated the historical TB Policy Research Working Paper Series.18
epidemic in the West and the present epidemic in de- Pearson correlation coefficients, R2 and P number
veloping parts of the world. The possibility that car- were calculated using Microsoft Excel mathematical
bon monoxide (CO) and particulate matter (PM) ac- functions. Pearson correlation is carried out with data
tivate the interleukin-10 (IL-10) anti-inflammatory from the corresponding figure for the given time period

Table Pearson partial correlation coefficients relating disease incidence or notification rate
(China), electrification and indicators of coal consumption in Canada, USA and China

Canada USA China

Employees in Electricity, Residential coal Total coal
Disease incidence the coal total number consumption, consumption
per 100 000 industry of customers million short tons in exajoules
population (1940–1975) (1940–1975) (1953–1990) (1982–2002)
TB 0.97 0.95 0.99* 0.95†
Typhoid fever 0.87 0.86
Whooping cough 0.85 0.87
Diphtheria 0.77 0.76
Scarlet fever 0.55 0.55
Poliomyelitis‡ 0.31 0.21

* Correlation in the US for residential coal is done with TB incidence/100 000 population. When using TB death rate/
100 000 in the US, the correlation was also 0.99.
† In China, TB notification rate/100 000 is used.
‡ Correlations for the period 1940–1964.

TB  tuberculosis.
724 The International Journal of Tuberculosis and Lung Disease

in the Table. Steel industry numbers, population data RESULTS

and electric drive figures for Norway are from Statis-
tike Centralbyrå,19,20 whereas TB mortality figures TB decline in twentieth century North America
(/100 000) are taken from Wood.21 The progress of Figure 2 shows the incidence of notified diseases and
urban gas lighting (total number of gas lights installed) BCG vaccination in Canada between 1926 and 1975.
in Paris is from Bouteville,22 whereas TB mortality There was a global downward trend of all diseases over
figures (/1000) in Paris are derived from Barnes.23 the period. TB incidence rose after 1930 (Figure 2A),
Waldron provides the number of notified workplace increased further with the advent of WWII to peak in
accidents during World War II,24 and TB historical 1944, and declined steadily after the war. In contrast,
statistics (total number of cases) for England and whooping cough increased around 1935, but not at
Wales are from the United Kingdom’s Statutory Noti- the onset of the war (Figure 2C). Scarlet fever shows
fications of Infectious Diseases (NOID).25 cyclic behaviour every 8 years or so (Figure 2D). An

Figure 2 Incidence of notified disease (A, C–F) in Canada during the twentieth century. Vertical dotted
lines highlight WW II. In B, BCG vaccination in the province of Quebec (solid line), in the province of New-
foundland (dotted line) and in the rest of Canada (dashed line) are shown. pop  population.
Air pollution caused by coal impacts on tuberculosis 725

outbreak of typhoid fever occurred in 1927; it de-

clined sharply then steadily afterwards, to almost dis-
appear (Figure 2E). Diphtheria also decreased after
1930, came back to some extent before WWII and
virtually disappeared after the war, presumably as a
consequence of vaccination (Figure 2F).
Of all the diseases shown in Figure 2, TB is perhaps
the disease most closely associated with WWII. This
can be explained by the arrival of the mass workforce
in manufactures involved in the war effort, considering
that factory and construction labourers were the prime
targets of TB in the 1930s.26 The cyclic behaviour of
scarlet fever was somewhat altered by the war, and
the increase in diphtheria may also have something to
do with living and working conditions during the war.
The number of BCG vaccine shots administered in
the province of Quebec, Newfoundland and the rest of
Canada are shown in Figure 2B. It is likely that BCG
vaccination had only a limited impact on the decline of
pulmonary TB in Canada and elsewhere after WWII.
First, TB decreased in countries where BCG was not ad-
ministered, such as the USA and the Netherlands. Sec-
ond, in Canada, the vaccine was mostly administered in
Quebec and Newfoundland (Figure 2B), and only ex-
ceptionally in the rest of Canada, whereas no bound-
aries were observed in TB incidence. Finally, BCG is a Figure 3 A. TB incidence (solid line), total number of coal
employees in the coal industry (dashed line) and electric utility
controversial vaccine, with an efficacy that has been re- customers (dotted line) in Canada between 1940 and 1975.
ported to vary between 0 and 80%.27 In addition, three B. Historical US domestic coal consumption (dashed line) and TB
meta-analyses carried out in the mid-1990s have shown incidence (solid line) between 1953 and 2003. pop  population.
a protective overall effect of 50%,28–30 with greater ef-
ficacy for disseminated forms and meningitis but lesser
efficacy in the case of pulmonary TB. was not administered (Figure 3B). Data for residential
As regards anti-tuberculosis drugs, streptomycin coal consumption in the USA are available. TB de-
(SM) did not become available before 1948, and resis- clines in the US again coincide with a reduction in res-
tance soon developed. Introduced in 1952, isoniazid idential coal consumption. A peak in TB incidence in
reduced resistance when used in combination with 1977 is visible and the increase in TB due to the HIV
SM.31 However, the decline in TB incidence in 1952 is epidemic between 1990 and 1997 can be seen. As for
not sharper than before, as could have been expected residential coal, its use has almost completely disap-
if the anti-tuberculosis drugs had had 100% effect peared by 1980.
(Figure 2A), and if it was administered systematically.
Figure 3A shows the number of coal workers, the Modern-day TB epidemic in China
number of customers of electric utilities and TB rates Overall coal consumption in China,16 when com-
in Canada after WWII, based on data obtained from pared to TB notification rates,17 shows an apparent
Statistics Canada.32 One important advance of the post- close relationship between global increases in coal con-
war era was the electrification of homes. In Canada, sumption and TB disease notification rates (Figure 4A).
gasoline and electricity replaced coal as the principle TB incidence and coal use have increased in a similar
means of heating households. The relative number of fashion in the last 20 years, with simultaneous peaks
coal workers during that period is used to illustrate around 1986, 1990 and 1996, and a corresponding
the decline of the coal industry in Canada, mainly due drop around 2000. In sharp contrast to trends in TB
to the loss of the residential market. In Canada, TB notifications and coal consumption in China, Figure
declined to levels below 20/100 000. This drop pre- 4B shows that overall poverty for rural and urban
cedes that of coal employees, which may reflect a de- areas decreased during the same period in China.18
lay in the lay off of the workforce relative to the evo- Social deprivation cannot, therefore, explain the in-
lution of the coal market. Nonetheless, the timelines crease in TB notifications (Figure 4A).
of TB decline and the indicators of residential coal China is the largest consumer and producer of coal in
consumption do coincide. the world. Today, coal is widely used in China as a
A similar pattern of TB decline is observed be- source of energy for both electricity production and
tween 1953 and 1975 in the United States, where BCG household use.33 Coal largely dominates the energy
726 The International Journal of Tuberculosis and Lung Disease

incidence between 1953 and 1990. The correlation of

0.95 between total coal consumption and TB notifi-
cation rate in China is also high.
The strong correlations in Canada, USA and China
between coal consumption and TB disease therefore
highlight the possibility that coal consumption directly
impacts on TB disease.

Coal and industrialisation

Before industrialisation in Europe, wood became scarce
and expensive, while coal became affordable. Char-
coal and coal combustion yield more energy than
wood; inventions and innovations led to the blast fur-
nace and the steam engine.
One key feature of industrialisation is the develop-
ment of the steel industry. The advent of this industry
may be considered a consequence of innovations in
the process of iron smelting. The blast furnace is a
metallurgical furnace used for smelting, notably iron
ore. Charcoal or coke, limestone and iron ore are fed
into the blast furnace while air is blasted at the bot-
tom. Iron is reduced to metal by charcoal, which
yields oxides of carbon as products of combustion.
Beginning in the UK in 1709, the use of coke (baked
Figure 4 A. Tuberculosis notification rates (solid line) and total bituminous coal) instead of charcoal (baked wood) in
coal consumption (dashed line) in China between 1980 and 2002. blast furnaces was of paramount importance in the
B. Poverty in China as a whole, in urban and rural areas: percent- advent of the industrial revolution, as it enabled the pro-
age of the population living in households with income per person
below the poverty line between 1981 and 2001. pop  population.
duction of iron that was cheaper and less brittle. In turn,
the availability of coal on the market spurred the use of
and technological innovations on the steam engine, as
landscape of the country;16 estimates suggest that 330 well as the development of heavy industry. This serves to
million people use coal for domestic purposes.34 Ac- illustrate how industrialisation boils down to coal.
cording to Finkelman et al., coal stoves and small coal
boilers provide more than 50% of the energy for urban TB and industrialisation
households, and 22% of rural households rely on coal.33
There is some agreement that TB incidence peaked
Low-grade coal is often burned in cheap, poorly vented
around 1800 in Western Europe.35 TB accounted for
or even unvented stoves, resulting in various illnesses.33
25% of deaths in New York city between 1810 and
1815.36 However, according to Barnes,23 TB in Paris
Correlation between energy and disease peaked around 1865, whereas in Norway it peaked
The Table correlates notified disease, coal employees around 1900.21 Therefore, based on the present hy-
and electrification in Canada between 1940 and 1975, pothesis, the peak in TB disease depends on the extent
and coal consumption and TB disease indicators in of air pollution and industrialisation in an area; in
China and the USA. The Pearson correlations are de- China, for example, industrialisation may be consid-
rived from the data used in Figures 2 and 3. ered to be occurring now.
In Canada, although the onset of TB precedes indi- TB numbers before the 1900s are difficult to find.
cators of residential coal consumption, the Pearson In Norway21 and Japan,4 for example, industrialisa-
partial correlation coefficient of 0.97 is strongest com- tion occurred later than in the rest of Europe, as did
pared to other notified diseases for the same period. It the rise in TB incidence.
is interesting to note that the negative correlation for Figure 5 shows TB incidence between 1855 and 1945
electricity of 0.95 is strongest for TB compared to in Norway. Beginning slowly around 1840, Norway in-
other diseases, as is the case for coal. Also, the corre- dustrialised its pulp and paper industry and introduced
lations for electric utility customers are similar in ab- steel works. The number of steel workers jumped from
solute value to those of coal employees for notified dis- 1608 to 7161 employees and from 9.3% to 22.8% of
ease in Canada, indirectly indicating that the electricity the total workforce between 1860 and 1870.19 The
market develops at the expense of the coal market. late onset of industrialisation, exemplified by the emer-
In the US, again, a very strong correlation of 0.99 gence of the steel industry in Norway (Figure 5), co-
is found linking residential coal consumption and TB incides with a delayed increase in TB incidence.
Air pollution caused by coal impacts on tuberculosis 727

and mainly composed of (vol%) H2 27–30%, CO 35–

45%, carbon dioxide (CO2) 10–15%, H2O 15–25%,
hydrogen sulphide (H2S) 0.2–1.2% and hydrogen
chloride (HCl) 50–500 ppm.40
A passage in the book by Flora Tristan describes a
scene at the coal gasification factory, the Gas Light
and Coke Company’s Horseferry Road Works, in
London in the 1830s:
Two rows of furnaces on each side were fired up [. . .]
The foreman told me that stokers were selected from
among the strongest, but that nevertheless they all
became consumptive after seven or eight years of toil
Figure 5 Mortality due to TB in Norway between 1855 and
and died of pulmonary consumption.41
1945 (solid line) with indicators of industrial development Town gas was first used for lighting streets and homes
shown on the timeline (diamonds). Electric motor drive in the
manufacturing industry between 1900 and 1938 in Norway
using the gaslight or ‘bec de gaz’. The first gaslights
(dashed line). pop  population. had a notoriously bad reputation: they were very in-
efficient and leaked large amounts of unburned gas
that added to the coal fumes in urban areas. An ac-
Another idiosyncrasy of Norway in regard to in- count by Lecouturier depicts industrialised Paris around
dustrialisation is the early electrification of the country, the 1850s:
early in the twentieth century, due to the abundance If you contemplate from the summit of Montmartre
of large water basins; the capacity of water plants the congestion of houses piled up at every point of a
jumped from 10 MW in 1907 to 1250 MW in 1920 vast horizon, what do you observe? . . . One is tempted
and to 2250 MW in 1939.37 to wonder whether this is Paris; and, seized with a
The TB epidemic receded earlier in Norway than sudden fear, one is reluctant to venture into this vast
in other industrialised countries such as the UK, Can- maze, in which a million beings jostle one another,
ada or the US. As illustrated in Figure 5, early electri- where the air, vitiated by unhealthy effluvia, rising in
a poisonous cloud, almost obscures the sun.23
fication, as exemplified by the use of electric motor
drive in the manufacturing industry between 1900 Figure 6A depicts the progress of urban gas lighting
and 1938, may explain the early decline in TB preva- in Paris—la ville lumière (the city of light)—during
lence in Norway, although the decline seemed to start the nineteenth century.22 Between 1831 and 1852, all
slightly before the onset of electrification. Neverthe- 13 000 urban lighting oil lamps of Paris were replaced
less, electrification proceeded very rapidly in Norway. by gaslights as gas pipelines were installed for urban,
Again, as was the case in Canada and the US, the industrial and domestic usage.
switch to a cleaner energy coincides with a dramatic In Paris, the TB epidemic peaked in the middle of
decrease in the prevalence of TB. the century, around 1865 (Figure 6B), and receded
In the late nineteenth century, Japan opened to the slowly thereafter.23 It may be considered that a critical
world following the Meiji restoration, and reforms factor for the acute crisis in Paris is the introduction
ensued. The silk industry financed the Meiji restora- of gaslight. As town gas allowed night shifts in manu-
tion to some extent. During the late nineteenth and early factures, it is likely that TB incidence increased among
twentieth centuries, the industrial production of silk factory labourers during the course of the nineteenth
in Japan was revolutionised by the use of steam boilers century. In defence of the thesis is the shift in sex ratio
for continuous, even heating of the reeling basins used for TB during that period: in 1830, two thirds of
to soften cocoons to be reeled into raw silk;38 coal was women suffered from TB, while in 1860 the trend re-
used to heat the steam boilers.39 TB incidence was high versed and two thirds of men suffered from TB;23 men
in the silk and spinning industry, and the young girls then constituted the majority of the labour force in
employed for spinning were the first victims. Later, a manufactures. The peak of the TB epidemic in Paris
second phase of heavy industrialisation in the 1930s around 1865 can therefore be explained by the wide-
shifted the trend, and young men became the prime spread use of town gas during that period. Thus, indi-
targets of TB (T Shimao, personal communication). rectly because of the advent of night shifts in the indus-
Back in Europe, in the early nineteenth century, try and directly due to town gas fumes, the utilisation
technical advances by the Scottish engineer William of combustible town gas is likely to have had an im-
Murdoch and others introduced town gas, also called pact on TB incidence during the nineteenth century.
synthetic gas or syngas. Town gas was produced by The decline in TB mortality towards the end of
gasification, a process whereby coal is heated in the that century may be explained by improved combus-
presence of water vapour. Syngas produced with coal tion and lighting technologies, such as the Auer lamp
in processes with water-coal slurry systems is typically invented by Dr Carl Auer von Welsbach in 1885,
728 The International Journal of Tuberculosis and Lung Disease

dents and the number of TB notifications in the UK

during WWII, showing a concomitant increase in
workplace accidents and TB in the UK during this
time. Generally speaking, there was an increase in all
types of workplace accidents. How can this be ex-
plained? According to Waldron, work was arduous in
UK factories during the war:
. . . a large and often inexperienced workforce spent
long hours in factories that were often poorly lit,
badly heated and badly maintained. The requirement
for complete blackout meant that ventilation systems
were often inadequate, and this resulted in greater
exposure than normal to some toxic substances. [. . .]
there is no question that the number of cases of spe-
cific industrial diseases increased substantially [. . .].24
It is possible that the increase in TB in the West during
WWII is due to working conditions in manufactures
involved in the war effort. In this regard, TB therefore
translates into an industrial disease, considering the
high rates of TB in construction and factory labourers
in the 1930s. It also highlights the possibility that a
specific workplace pollutant is involved in reactiva-
tion of the disease. Generally speaking, if poverty was
such an important factor in the incidence of TB, the
Figure 6 A. Total numbers of urban lighting oil lamps (grey) disease would have increased mostly in the 1930s, as
and town gas lamps (black) installed in Paris in 1831, 1848 and
poverty was rampant during the Great Depression.
1852. B. TB mortality rates in Paris during the nineteenth cen-
tury. pop  population. Considering that ventilation in the workplace was
less than satisfactory in the first half of the twentieth

whose use spread around 1890. It may be noteworthy

to mention that town gas is still used in industrialising
parts of the world today where natural gas is rare or
expensive, such as in China or South Africa.42
TB, industry and ventilation
In a 1930 occupational hazards study, construction
and factory labourers were found to be the prime tar-
get of TB, with a death rate of 227.3/100 000 com-
pared to 180.0 for waiters, 173.3 for servant classes,
165.6 for teamsters and carriage drivers, 106.0 for
coal mine operatives and 23.7 for physicians and sur-
geons,26 trends that are in sharp contrast with today’s
occupational statistics.
The prevalence of TB in industry and manufac-
tures is a recurrent theme during the nineteenth and
twentieth centuries. A 1914 paper by Hastings directly
links TB and air pollution:
Among garment workers many cases of tuberculosis
develop. This is due largely to long hours, dusty, badly
ventilated, overcrowded rooms, in which they fre-
quently use gas stoves, or gas flat irons and charcoal
stoves. Cases of chronic gas poisoning are not unusual
among these people from leaky gas stoves.43
TB made a comeback in the West during WWII. The
war effort brought masses of workers into manufac- Figure 7 Reported workplace accidents in factories and tuber-
culosis notifications between 1937 and 1946 in the UK, show-
tures. Figure 7A shows carbon monoxide, nitrous ing A) number of carbon monoxide (solid line), nitrous fumes
fumes and lead intoxications in UK manufactures, (dashed line) and lead (dotted line) poisoning notifications; and
while Figures 7A and 7B compare intoxication acci- B) total number of pulmonary TB notifications.
Air pollution caused by coal impacts on tuberculosis 729

century, it is conceivable that the high incidence of TB fied as risk factors for TB, and social factors may not
in manufactures is explained by workplace air pollut- convincingly explain the aetiology of the disease.5
ants. Electricity gradually replaced internal combus- The US Environmental Protection Agency esti-
tion engines as the source of mechanical drive, and mated US coal emissions in 2000 by fuel combustion
proper ventilation systems were installed in the indus- electric utilities for the principal pollutants: sulphur
try. These changes occurred in parallel to the shift in dioxide (SO2) 10 723 thousand short tons (tst), nitro-
household energy sources, thereby reducing the total gen oxides (NOx) 4573 tst, CO 234 tst, PM 10 m
burden of air pollution. (PM10) 242 tst, PM 2.5 m (PM2.5) 116 tst, volatile
Pertaining to the issue of ventilation, ‘open-air treat- organic compounds (VOC) 30 tst, and lead (Pb) 56
ment’ or ‘sanatorium treatment’ was introduced in short tons.49
Germany by Hermann Brehmer in Görbersdorf, Sile- The prime pollutant in coal is SO2, followed by
sia, in 1854.44 Although some variations existed be- NOx. CO is substantially less, but partial combustion
tween sanatoria (e.g., rest vs. exercise, altitude vs. sea of coal is known to produce large amounts of CO,
level), open-air treatment was essentially based on ex- and it has been suggested that US tabulated data for
posing the patient to fresh air, night and day, in a re- CO emissions may be underestimated.50 Ash from coal
mote area. In studies of sanatoria in England, it has combustion, or PM, is composed primarily of oxides
been said that patients increased in weight within the of silicon, aluminium and iron. On the whole, coal is
first week (2–6 pounds), cough was seldom heard, and considered to be a very polluting fuel.
night sweats tended to cease within days.45,46 Sanatoria Bygone coal furnace technologies are likely to have
were generally considered beneficial. Strangely enough, had an impact on indoor air pollutants and CO levels.
no comparative study on the efficacy of sanatoria was They were not nearly as efficient as they are today, and
ever carried out. Bardswell made a careful follow-up therefore resulted in partial combustion of coal, indoor
study of patients admitted to the King Edward VII build-up of CO and heavy PM emissions. Today in
sanatorium in Sussex between 1907 and 1914.47 He China, low-grade coal is often burned in cheap, poorly
found that by 1916, 751 of 1707 (44%) patients had vented or even unvented stoves, resulting in various ill-
died, making sanatoria less than a panacea. In retro- nesses.33 In addition, keeping stockpiles of moist lignite
spect, and in the light of the present hypothesis, the coal near a source of heat will result in CO leakage, a
sanatorium treatment may be regarded as a way to process reminiscent of industrial coal gasification.
keep patients away from polluted urban, industrial Considering the present hypothesis, the impact of
and domestic environments. coal on TB disease should transpose into a specific
mechanism in vivo. A closer look at the physiological
effects of CO and the biology of TB suggests a plau-
sible mechanism whereby coal fumes shut down the
The present analysis suggests that air pollution result- immune response of the host.
ing from coal combustion directly affects TB incidence. Termed the silent killer, CO is an odourless, taste-
Although the decrease in TB observed in the West can less and colourless gas with a well-known tendency to
be explained by socio-economic factors, the use of build up indoors. Identified in recent years as an intra-
anti-tuberculosis drugs and/or the BCG vaccine, the cellular signalling molecule, CO is generated endoge-
coincidence with coal consumption is nothing short nously by haeme oxygenase enzymes (HOs). The IL-10
of troubling. anti-inflammatory pathway requires the activation of
In China, HIV prevalence is low48 and therefore haeme oxygenase-1 (HO-1), which degrades the haeme
cannot explain the increase in TB in the last 20 years. of haemoglobin, yielding CO, biliverdin and iron as
The correlation may, however, reflect a direct associ- by-products.51 Anti-inflammatory action was found
ation between coal consumption and TB incidence. In to be mediated by CO, as its removal blocks the effects
the case of China, notification rate instead of TB inci- of IL-10 and HO-1.52 A major effect of CO is the down-
dence was used (Figure 4). It should be added that a regulation of tumour necrosis factor-alpha (TNF-).
better health system in a wealthier state can result in TNF- plays a central role in the formation of
increased TB notifications. granulomata and containment of TB.53,54 Inhibition
Generally speaking, the evidence presented in the of TNF- by drugs on trial has been linked to reacti-
present paper should be regarded with caution given vation of TB.55,56 In addition, macrophages are of par-
the inherent limitations of the ecological approach. amount importance in the defence against M. tuber-
The correlations are prone to the ecological fallacy, culosis. Growth inhibition is mostly mediated by
because no confounders can be tested. For example, nitrogen oxide NO species57–60 promoted by TNF-.
in Canada, the overall improvement of the health sys- Interferon-gamma (IFN-) and TNF- are central
tem after WWII, concomitant with the electrification to the process, as they induce macrophage activation,
of cities, could explain a global decrease in TB. Nev- inducible nitric oxide synthase (iNOS) expression and
ertheless, it is an hypothesis to be investigated, as bio- NO generation.60,61
mass cooking fuel7 and cigarettes9 have been identi- On the other hand, M. tuberculosis encodes trun-
730 The International Journal of Tuberculosis and Lung Disease

cated haemoglobins (trHbs) whose function remains suggested that Slc11a1 influences susceptibility to TB
unclear. TrHbs have been associated with protection by regulation of IL-10 because a polymorphism in
against nitrosative damage by virtue of their NO di- Slc11a1 was associated not only with TB, but also with
oxygenase activity, utilisation of CO as a carbon a higher endotoxin-induced production of IL-10.70 In
source, O2/NO sensing, redox reactions, O2 delivery the scope of the CO-doping model, modification of
in hypoxic conditions and long term ligand/substrate the iron pool by Slc11a1 serves to desensitise the IL-10
storage.62–66 M. tuberculosis trHb has, along its haeme pathway in lung macrophages or to capture available
group, an a-polar tunnel system through the protein iron used in trHb haeme, thereby impacting on the
matrix endowed with more than one entry/exit points anti-inflammatory activity of CO and/or the ability of
and is able to store diatomic molecules in its cavity.67 M. tuberculosis to feed macrophages with CO.
The model shown in Figure 8 details a mechanism Another issue yet to be considered is the link be-
whereby M. tuberculosis responds to macrophage ni- tween PM from coal combustion and the activation
trosative attack with the release of CO stored in trHb of the IL-10 pathway in fibrotic lungs. It is known
molecules, followed by suppression of immunity, a that miners in coal and gold mines are more prone to
model termed ‘CO-doping’. In addition to actively TB as a result of silicosis.10,11 It has been shown that,
protecting the bacilli through NO oxidation by trHb in mice, the IL-10 pathway is activated in the course
nitric dioxygenase activity, CO-doping functions to of fibrosis of the lung,71,72 but not in rats.
induce an IL-10-like response. As a result, a decline in Coal ash differs from wood ash, which could ex-
TNF- production, macrophage activation and cell- plain an enhanced activation of TB by coal as opposed
mediated immunity ensues. In either case, irrespective to wood; TB existed before industrialisation, but pre-
of the capacity of M. tuberculosis to actively trigger sumably to a lesser extent. Logically, the amount of
the IL-10 pathway, elevated ambient levels of CO re- CO produced by the combustion of coal should be
sult in lower levels of TNF- through activation of greater than that produced by the combustion of wood.
the IL-10 pathway. In combustion experiments for different fuels in a lab-
It is noteworthy to add that polymorphism in the oratory system designed to mimic the fire pit used in
slc11a1 (formerly Nramp1) gene has been identified Xuan Wei County in China, emissions of anthracite,
as a factor of resistance to TB in mice.68 slc11a1 is bituminous coal and pine wood were compared.73
thought to be an iron transporter localised to mem- These results show that the total PM emissions for bi-
branes of phagocytes in macrophages. Polymorphisms tuminous coal were 5.6-fold those of pine wood,
in IL-10 and TNF- have also been linked to pulmo- whereas there were only 1.6-fold more CO emissions
nary TB.69 The precise role of Slc11a1 in TB resis- for bituminous coal than for pine wood. However, in
tance remains to be elucidated: however, it has been China, the use of cheap grades of coal such as moist
lignite may result in worse figures for CO.33
In conclusion, coal, the workhorse of progress,
seems an inevitable step in the emergence of an indus-
trialised country. Thus, in the light of the present hy-
pothesis, the white plague will rise and vanish along
the path of entry into modernity; the disease will fluc-
tuate in the population in a complex interplay of fac-
tors: domestic and industrial use of various types of
coal, combustion technologies, the number and gender
of workers in manufactures, and the source of mechan-
ical drive. Finally, as electrification progresses and pov-
erty plummets, TB regresses to a bad memory—until
AIDS brings it back on topic. Jean and René Dubos,
in their book The White Plague, called TB a disease of
‘incomplete civilization’.74 It could also be said that
TB is a disease of incomplete industrialisation.
Although micro-organisms are causative agents of
many illnesses, environmental health factors are not
Figure 8 CO-doping model in the reactivation of latent tuber-
culosis. Release to macrophages of CO stored in trHb of M. to be underestimated in the aetiology of the disease.
tuberculosis, mimicking the IL-10 anti-inflammatory pathway, The present evidence should prompt investigators to
results in inhibition of gene transcription, TNF- production and study the effects of air pollution, notably coal, in re-
leads to reduced macrophage activation, nitric oxide produc- gard to TB. An epidemiological approach that can
tion and cell-mediated immunity. CO  carbon monoxide; LPS  take into account confounders could substantiate the
lipopolysaccharide; TLR  toll-like receptor; trHb  truncated
haemoglobins; TNF  tumour necrosis factor; NO  nitric ox- hypothesis. Furthermore, the impact of various air
ide; HO  haeme oxygenase; IL-10  interleukin-10; iNOS  pollutants on the outcome of TB should be investi-
inducible nitric oxide synthase. gated in animal models.
Air pollution caused by coal impacts on tuberculosis 731

Acknowledgements 24 Waldron H A. Occupational health during the Second World

War: hope deferred or hope abandoned? Med Hist 1997; 41:
I would like to thank Dr D Menzies for critical review of the manu-
script. I am also grateful to Dr T Shimao for information on histor-
25 Tuberculosis—respiratory and non-respiratory notifications,
ical facts pertaining to TB in Japan.
England and Wales, 1913–2004: Communicable Disease Sur-
veillance Centre (CDSC). London, UK: Health Protection
Agency, 2005.
References 26 Sepkowitz K A. Tuberculosis and the health care worker: a his-
1 Havlir D V, Barnes P F. Tuberculosis in patients with human torical perspective. Ann Intern Med 1994; 120: 71–79.
immunodeficiency virus infection. N Engl J Med 1999; 340: 27 Fine P E M. Bacille Calmette-Guérin vaccines: a rough guide.
367–373. Clin Infect Dis 1995; 20: 11–14.
2 World Health Organization. WHO report 2006. Global tuber- 28 Rodrigues L C, Diwan V K, Wheeler J G. Protective effect of
culosis control: surveillance, planning, financing. WHO/HTM/ BCG against tuberculous meningitis and miliary tuberculosis:
TB/2006.362. Geneva, Switzerland: WHO, 2006. a meta-analysis. Int J Epidemiol 1993; 22: 1154–1158.
3 Grigg E R N. The arcana of tuberculosis, with a brief epidemi- 29 Colditz G A, Berkey C S, Mosteller F, et al. The efficacy of ba-
ologic history of the disease in the USA. Am Rev Tuberc Pulm cillus Calmette-Guerin vaccination of newborns and infants in
Dis 1968; 78: 151–172. the prevention of tuberculosis: meta-analyses of the published
4 Shimao T. Mortality rate of pulmonary TB in the late 19th cen- literature. Pediatrics 1995; 96: 29–35.
tury. Kekkaku 2003; 78: 633–636. 30 Colditz G A, Brewer T F, Berkey C S, et al. Efficacy of BCG
5 Davies R P O, Tocque K, Bellis M A, Remmington T, Davies vaccine in the prevention of tuberculosis. Meta-analysis of the
P D O. Historical declines in tuberculosis in England and Wales: published literature. JAMA 1994; 271: 698–702.
improving social conditions or natural selection? Vesalius 1999; 31 Grzybowski S, Allen E A. Tuberculosis: 2. History of the dis-
5: 25–29. ease in Canada. CMAJ 1999; 160: 1025–1028.
6 Marie-Davy H. Revue d’hygiène 1911; 33: 714. 32 Landes D S. The unbound Prometheus: technological change
7 Mishra V K, Retherford R D, Smith K R. Biomass cooking fuels and industrial development in Western Europe from 1750 to the
and prevalence of tuberculosis in India. Int J Infect Dis 1999; 3: present. Cambridge, UK: Cambridge University Press, 1969.
119–129. 33 Finkelman R B, Belkin H E, Zheng B. Health impacts of do-
8 Gupta B N, Mathur N. A study of household environmental mestic coal use in China. Proc Natl Acad Sci USA 1999; 96:
risk factors pertaining to respiratory diseases. Energy Environ 3427–3431.
Monitor 1997; 13: 61–67. 34 Smith K R, Liu Y. Epidemiology of lung cancer. New York, NY,
9 Gajalakshmi V, Peto R, Kanaka T S, Jha P. Smoking and mor- USA: Marcel Dekker, 1994.
tality from tuberculosis and other diseases in India: retrospec- 35 Murray J F. A century of tuberculosis. Am J Respir Crit Care
tive study of 43 000 adult male deaths and 35 000 controls. Med 2004; 169: 1181–1186.
Lancet 2003; 352: 507–515. 36 Holmberg S D. The rise of tuberculosis in America before
10 Rockette H E. Cause-specific mortality of coal miners. J Occup 1820. Am Rev Respir Dis 1990; 142: 1228–1232.
Med 1977; 17: 795–801. 37 Venneslan C. Labour markets and recovery of the great depres-
11 Godfrey-Faussett P, Sonnenberg P, Shearer S C, et al. Tubercu- sion in Norway. XIV International Economic History Congress.
losis control and molecular epidemiology in a South African Helsinki, Finland: International Economic History Association,
gold-mining community. Lancet 2000; 356: 1066–1071. 21–25 August 2006, Session 10.
12 Statistics Canada. Historical statistics of Canada, catalog 11- 38 Ma D. Between cottage and factory: the evolution of Chinese
516-XIE. Ottawa, Canada: Statistics Canada, 1983. and Japanese silk-reeling industries in the latter half of the 19th
13 Malissard P. La longue controverse de la vaccination antituber- century. Asia Pacific Economy 2005; 10: 195–213.
culeuse au Canada : le bacille Calmette-Guérin (BCG), 1925– 39 Sugiyama S, Yamada I. The problem of fuel: an economic his-
1975. Canadian Bulletin of Medical History 1998; 15: 87–128. tory of the environment with reference to the Nagano silk reel-
14 United States Department of Energy. Annual energy review ing industry. Shakai keizai shigaku 1999; 65: 3–24. [Japanese]
2005. Washington, DC, USA: Energy Information Administra- 40 Wakker B. High temperature corrosion in gasifiers. Materials
tion, DOE, July 2006. Res 2004; 7: 53–59.
15 Centers for Disease Control and Prevention. Reported tubercu- 41 Tristan F. Promenades dans Londres, 1842, l’aristocratie et les
losis in the United States, 2005. Atlanta, GA, USA: US Depart- prolétaires anglais. Paris, France: Indigo & Côté-femmes, 2001.
ment of Health and Human Services, CDC, September 2006. 42 Winter C J, Nitch J. Hydrogen as an energy carrier. New York,
16 National Bureau of Statistics. China statistical yearbook 2003. NY, USA: Springer Verlag, 1988.
Beijing, China: National Bureau of Statistics, 2003a. 43 Hastings C. Industrial disease and industrial hygiene. Can Med
17 World Health Organization. WHO report 2005. Country pro- Assoc J 1914; 4: 782–792.
file of China. Geneva, Switzerland: WHO, 2005. 44 McCarthy O R. The key to the sanatoria. J R Soc Med 2001;
18 Ravallion M, Chen S. China’s (uneven) progress against pov- 94: 413–417.
erty. World Bank Policy Research Working Paper No. 3408. 45 Philip R W. Further experiences in the open-air treatment of
Washington, DC, USA: World Bank, 2004. phthisis. Practitioner 1899; 10: 11–21.
19 Rygg N. Statistike oversigter. Oslo, Norway: Statistik sentral- 46 Burton-Fanning F W. The open-air treatment of phthisis in
byrå, 1914. England. Lancet 1898; i: 630–633, 712–616, 854–637.
20 Norges offisielle statistikk Fjerde Række. Industristatistikk Nr. 47 Bardswell N D, Thompson J H R. Mortality after sanatorium
99–NOS X. 44 (1895–1939). Oslo, Norway: Statistik cen- treatment. Med Res Committee Spec Rep 1919; 33: 1–112.
tralbyrå, annual publications. 48 Joint United Nations Programme on HIV/AIDS. Report on the
21 Wood S R. A contribution to the history of tuberculosis and lep- global AIDS epidemic. Geneva, Switzerland: UNAIDS, 2006.
rosy in 19th century Norway. J Roy Soc Med 1991; 84: 428–431. 49 United States Environmental Protection Agency. National air
22 Bouteville R. L’éclairage public à Paris. Paris, France: Léon Ey- quality and emissions trends report. Research Triangle Park,
rolles, 1925. NC, USA: US EPA, 2004.
23 Barnes D S. The making of a social disease: tuberculosis in 50 Nicks D K J, Holloway J S, Ryerson T B, et al. Fossil-fuelled
nineteenth century France. Berkeley, CA, USA: University of power plants as a source of atmospheric carbon monoxide.
California Press, 1995. J Environ Monit 2003; 5: 35–39.
732 The International Journal of Tuberculosis and Lung Disease

51 Maines M D. The heme oxygenase system: update 2005. HbN protects Mycobacterium bovis from nitric oxide. Proc
Antioxid Redox Signal 2005; 7: 1761–1766. Natl Acad Sci USA 2002; 99: 5902–5907.
52 Otterbein L E, Bach F H, Alam J, et al. Carbon monoxide has 63 Park S W, Hwang E H, Park H, et al. Growth of mycobacteria
anti-inflammatory effects involving the mitogen-activated pro- on carbon monoxide and methanol. J Bacteriol 2003; 185:
tein kinase pathway. Nat Med 2000; 6: 422–428. 142–147.
53 Mohan V P, Scanga C A, Yu K, et al. Effects of tumour necrosis 64 Wittenberg J B, Bolognesi M, Wittenberg B A, et al. Truncated
factor alpha on host immune response in chronic persistent haemoglobins: a new family of haemoglobins widely distrib-
tuberculosis: possible role for limiting pathology. Infect Immun uted in bacteria, unicellular eukaryotes and plants. J Biol Chem
2001; 69: 1847–1855. 2002; 277: 871–874.
54 Van Deventer S J H. Transmembrane TNF-, induction of apo- 65 Gardner P R, Gardner A M, Martin L A, et al. Nitric-oxide di-
ptosis, and the efficacy of TNF-targeting therapies in Crohn’s oxygenase activity and function of flavohaemoglobins. Sensi-
disease. Gastroenterol 2001; 121: 1242–1246. tivity to nitric oxide and carbon monoxide inhibition. J Biol
55 Keane J, Gershon S, Wise R P, et al. Tuberculosis associated Chem 2000; 275: 31581–31587.
with infliximab, a tumour necrosis factor alpha-neutralizing 66 Mukai M, Mills C E, Poole R K, et al. Flavohaemoglobin, a
agent. N Engl J Med 2001; 345: 1098–1104. globin with a peroxidase-like catalytic site. J Biol Chem 2001;
56 Wagner T E, Huseby E S, Huseby J S. Exacerbation of Myco- 276: 7272–7277.
bacterium tuberculosis enteritis masquerading as Crohn’s 67 Milani M, Pesce A, Ouellet Y, et al. Heme-ligand tunneling in
disease after treatment with a tumour necrosis factor-alpha in- group I truncated haemoglobins. J Biol Chem 2004; 279: 21520–
hibitor. Am J Med 2002; 112: 67–69. 21525.
57 Ehrt S, Schnappinger D, Bekiranov S, et al. Re-programming of 68 Kramnik I, Dietrich W F, Demant P, et al. Genetic control of re-
the macrophage transcriptome in response to interferon- sistance to experimental infection with virulent Mycobacterium
gamma and Mycobacterium tuberculosis: signalling roles of ni- tuberculosis. Proc Natl Acad Sci USA 2000; 97: 8560–8565.
tric oxide synthase-2 and phagocyte oxidase. J Exp Med 2001; 69 Delgado J C, Baena A, Thim S, et al. Ethnic-specific genetic
194: 1123–1140. associations with pulmonary tuberculosis. J Infect Dis 2002;
58 MacMicking J D, North R J, LaCourse R, et al. Identification 186: 1463–1468.
of nitric oxide synthase as a protective locus against tuberculo- 70 Awomoyi A A, Marchant A, Howson J M M, et al. Interleukin-
sis. Proc Natl Acad Sci USA 1997; 94: 5243–5248. 10, polymorphism in SLC11A1 (formerly NRAMP1), and sus-
59 Chan J, Tanaka K, Carroll D, et al. Effects of nitric oxide syn- ceptibility to tuberculosis. J Infect Dis 2002; 186: 1808–1814.
thase inhibitors on murine infection with Mycobacterium 71 Barbarin V, Nihoul A, Misson P, et al. The role of pro- and
tuberculosis. Infect Immun 1995; 63: 736–740. anti-inflammatory responses in silica-induced lung fibrosis.
60 Chan J, Xing Y, Magliozzo R S, et al. Killing of virulent Myco- Respir Res 2005; 6: 1–13.
bacterium tuberculosis by reactive nitrogen intermediates pro- 72 Huaux F, Louahed J, Hudspith B, et al. Role of interleukin-10
duced by activated murine macrophages. J Exp Med 1992; 175: in the lung response to silica in mice. Am J Respiratory Cell
1111–1122. Mol Biol 1998; 31: 78–85.
61 Manca C, Tsenova L, Barry C E, et al. Mycobacterium tuber- 73 Tian L. Coal combustion emissions and lung cancer in Xuan
culosis CDC1551 induces a more vigorous host response in Wei, China. Environmental Sciences Dissertation. Berkeley,
vivo and in vitro, but is not more virulent than other clinical CA: University of California, Berkeley, 2005: p 221.
isolates. J Immunol 1999; 162: 6740–6746. 74 Dubos R, Dubos J. The white plague: tuberculosis, man, and so-
62 Ouellet H, Ouellet Y, Richard C, et al. Truncated haemoglobin ciety. New Brunwsick, NJ, USA: Rutgers University Press, 1987.


On considère généralement que la tuberculose (TB) va la maladie doivent encore être déterminés. On met en
de pair avec l’industrialisation et l’urbanisation. Avec un corrélation les statistiques historiques de consommation
pic dans les années 1800 et une lente régression ultérieure, de charbon et de maladie TB au Canada, aux USA et en
la maladie a décliné fortement en Occident après la deu- Chine. On élabore une hypothèse liant la TB et la pollu-
xième guerre mondiale. La TB fait un retour dans les 20 tion de l’air dans le contexte de l’industrialisation. Un
dernières années dans les pays en développement comme modèle est proposé dans lequel la stimulation de la cascade
la Chine et l’Inde. Comme les seules conditions socio- IL-10 par le monoxyde de carbone dans les macrophages
économiques ne peuvent pas expliquer la connexion entre pulmonaires favorise la réactivation de Mycobacterium
l’industrialisation et la TB, des facteurs étiologiques de tuberculosis.


La tuberculosis (TB) se considera generalmente vincu- tribuyen a la etiología de la enfermedad. Las estadísticas
lada con la industrialización y la urbanización. La enfer- históricas de consumo de carbón presentan una correla-
medad presentó el pico de frecuencia más alto en el siglo ción con la incidencia de tuberculosis en Canadá, los
XIX, declinó luego lentamente y mostró una dismi- Estados Unidos y China. Se plantea una hipótesis que
nución drástica después de la segunda guerra mundial, asocia la TB con la contaminación atmosférica en el
en Occidente. Durante los últimos 20 años, la TB ha sur- contexto de la industrialización. Se propone un modelo
gido de nuevo en países en desarrollo como China e según el cual la activación de la cascada de la inter-
India. Puesto que las condiciones socio-económicas por leucina 10 por el monóxido de carbono en los macrófa-
sí solas no explican la correlación entre industrialización gos del pulmón promueve la reactivación de Mycobacte-
y TB, deben determinarse los demás factores que con- rium tuberculosis.