- Email: [email protected]
Viraemia and faecal shedding of HEV in symptom-free carriers
CORRESPONDENCE
progestagens might have harmful orally effects on the breast,3 administered progestagens may have a detrimental effect on the breast,3 orally administered progestagens would not be acceptable to women taking tamoxifen to lower their chance of developing breast cancer. Direct administration of progestagen to the endometrium effectively protects it with little or no systemic effect. Although not licensed for this use, the use of a progestagen or levonorgestrelreleasing intrauteruine system might have protective effects against tamoxifen. If so, many women could continue with tamoxifen, rather than being deprived of the substantial benefits it offers against development of primary breast carcinoma.4 *M J Dickson, T Pandiarajan Department of Obstetrics and Gynaecology, Copeland Offices, Birch Hill Hospital, Rochdale, Lancashire OL12 9QB, UK 1
2
3
4
Bergman L, Beelen MLR, Gallee MPW, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Lancet 2000; 356: 881–87. Ismail SM. Pathology of endometrium treated with tamoxifen. J Clin Pathol 1994; 47: 827–33. Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000; 283: 485–91. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998; 90: 1371–88.
Sir—Liesbeth Bergman and colleagues1 use epidemiological data associated with endometrial cancer to rebut advocates for tamoxifen use in healthy women. Clinical neuropsychological testing is necessary before tamoxifen use in healthy women is recommended. Cognitive deficits are seen when formal neuropsychological testing is done on breast-cancer patients treated with chemotherapy plus tamoxifen or chemotherapy alone.2 Tamoxifen acts as a non-competitive block to the ligated serotonin channel in the central nervous system.3 Subtests that assess memory, executive function, visual perception, and motor dexterity should be highlighted. Visual performance with the starry night task test and motion discrimination using low and high velocity dot kinetogram might document the organic explanation for women’s visual blurring complaints while on tamoxifen. Pamela Kairies 3647 Cedarbrae Lane, San Diego, CA 92106, USA 1
68
Bergman L, Beelen MLR, Gallee MPW, et al. Risk and prognosis of endometrial
2
3
cancer after tamoxifen for breast cancer. Lancet 2000; 356: 881–87. Schagen S, van Dam F, Muller M, Boogerd W, Lindeboom J, Bruning P. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 1999; 85: 640–50. Allen M, Newland C, Valverde M, Hardy S. Inhibition of ligand-gated cation-selective channels by tamoxifen. Eur J Pharmacol 1998; 354: 261–69.
Sir—Liesbeth Bergman and colleagues1 show risk of endometrial cancer increases with increasing duration of tamoxifen use. More importantly, they show that women who develop endometrial cancer have a worse outlook, less favourable histology, higher stage, and later prescription than previously thought. Although tamoxifen has oestrogenantagonistic effects on breast-cancer cells, it has oestrogen-agonistic activity at other sites, including the endometrium and bone.2 Exposure to unopposed oestrogen increases the risk of endometrial hyperplasia and cancer, and a progestagen is generally added to hormone-replacement therapy to protect the endometrium. The oestrogen-agonistic activity of tamoxifen on the uterus mimics exposure of the endometrium to unopposed oestrogen, It would, therefore, seem sensible to investigate the use of progestagens to protect the endometrium in patients using tamoxifen. Whether progestogens exert a beneficial or harmful effect on the initiation or promotion of breast cancer seems unclear. Progestogens have been used in the treatment of metastatic breast cancer and response rates are similar to that of tamoxifen. However an observational study has suggested that combined oestrogen and progesterone hormone-replacement therapy seems to increase patients’ risks of developing breast cancer compared with oestrogen therapy alone.3 A prospective study on apes might shed more light on this dilemma, suggesting that oestrogenic activity is necessary for progestagens to have a harmful effect on the breast.4 Given the prevalence of breast cancer, it is not surprising that thousands of women in the UK are taking tamoxifen. The Breast Cancer Prevention Trial in the USA5 showed that women with an increased genetic risk of developing breast cancer had a 45% reduction in that risk if they took tamoxifen. If the results of that trial are substantiated, thousands more women will undoubtedly be keen to take tamoxifen. Physicians and patients need clear guidelines as to how best monitor and protect the endometrium from the
unwanted side-effects of tamoxifen, or both. At present, patients are encouraged to report symptoms of vaginal discharge or bleeding. For some this sign may be too late. The medical profession needs to look closely at the risks, benefits, and cost effectiveness of combining progestagens with tamoxifen. If progestagens are beneficial to these patients they may be better delivered to the endometrium locally (eg, the intrauterine levonorgestrel system) to avoid unwanted systemic side-effects. *Fiona Marsh, Martin Mayfield (e-mail: [email protected]) 1
2
3
4
5
Bergman L, Beerlen MLR, Gallee MPW, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Lancet 2000; 356: 881–87. Dixon M, Sainsbury R. Diseases of the Breast, 2nd edn. London: Churchill Livingstone: 147: 1998. Schairer C, Lubin J, Troisi R, et al. Menopausal oestrogen and oestrogenprogesterone replacement therapy and breast cancer risk. JAMA 2000; 238: 485–91. Cline JM, Soderqvist G, Von Shoultz, et al. Effects of conjugated oestrogens, medroxyprogesterone acetate and tamoxifen on the mammary glands of macaques. Breast Cancer Res Treat 1998; 48: 221–29. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel project P-1 study. J Natl Cancer Inst 1998; 90: 1371–88.
Viraemia and faecal shedding of HEV in symptom-free carriers Sir—Rakesh Aggarwal and colleagues (Sept 23, p 1081)1 report that hepatitis E virus (HEV) RNA is not detected in stool or serum samples beyond the phase of clinical course and biochemical hepatitis. They conclude that recovered patients are unlikely to serve as reservoirs in HEV-endemic areas. We provide complementary data that may clarify the potential human reservoir of HEV during epidemics. From August, 1999, to November, 1999, we investigated an outbreak of clinical acute hepatitis among Albanian Kosovar refugees returning home to Mitrovica after the withdrawal of the Serbs from Kosovo. This outbreak was spotted early because of the epidemiological and biological collaborations between the Institute of Public Health of Mitrovica and the French Military Health Service. With informed consent, we tested 103 Albanian Kosovars (age 2–50 years [mean 13·6]) and two French members of non-governmental
THE LANCET • Vol 357 • January 6, 2001
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE
Individual’s Geographic Clinical Sex Age IgG and HEV RNA in serum* number origin characteristics (years) IgM to HEV
⫺
⫺ (3 samples collected on days 12, 21, 45) ⫺ (1 sample collected on day 8) + (1 sample collected on day 15) ⫺ (1 sample collected on day 8) ⫺
⫺ (1 sample collected on day 30) + (1 sample collected on day 15) +
⫺ ⫺ ⫺
+ ⫺ +
NA + NA
1
Kosovar
Acute hepatitis
M
46
+
2
French
Acute hepatitis
M
28
+
3
Kosovar
Acute hepatitis
F
5
⫺
4
Kosovar
Acute hepatitis
F
11
⫺
5
Kosovar (wife of index case) Kosovar Kosovar Kosovar (twin of number 7)
Symptom-free
F
42
Symptom-free Symptom-free Symptom-free
M M F
8 10 10
6 7 8
HEV RNA in stools ⫺ (1 sample collected on day 45) NA
NA=not available. *Date of collection of samples after onset of symptoms.
2
3
4
faecal viral excretion in acute hepatitis E. Lancet 2000; 356: 1081–82. Caudill JD, Malik IA, Tsarev SA. Evidence for human hepatitis E virus (HEV) infection without acute antibody response. Am J Trop Hyg 1994; 51: 201. Clayson E, Myint KS, Snitbhan E, et al. Viraemia, fecal shedding and IgM and IgG responses in patients with hepatitis E. J Infect Dis 1995; 172: 927–33. Touze A, Enogat N, Buisson Y, Coursaget P. Baculovirus expression of chimeric hepatitis B core particles with hepatitis E epitopes and their use in a hepatitis E immunoassay. J Clin Microbiol 1999; 37: 438–41.
Public health and air pollution
Epidemiological characteristics and hepatitis E markers
organisations ([NGOs] aged 28 and 30 years) who had clinical acute hepatitis for serological hepatitis markers. We also investigated 27 symptom-free individuals (age 7–41 years [mean 13·1]) who were household or school contacts of cases. Most of the acute hepatitis cases (90 of 105), including the two NGO members, and five symptom-free contacts had antibodies to hepatitis A virus. A Kosovar aged 46 years from whom we took samples on days 12, 21, and 45 after the onset of first symptoms, and one Frenchman sampled on day 8 were strongly reactive for IgG antibodies to HEV and IgM to HEV, which confirmed the diagnosis of acute hepatitis E. HEV RNA was searched by RTPCR in all serum and in stool samples (collected for a few individuals). HEV RNA was undetectable in three sequential serum samples from the Kosovar index case and in the NGO member (table). Two children with acute hepatitis had HEV RNA in one serum sample (number 3) and in a stool sample (number 4, table) taken on day 15 after the onset of first symptoms, but tested negative for IgM and IgG to HEV. Viraemia and faecal shedding were detected in four symptom-free contacts who were seronegative for HEV antibodies. The follow-up of these contacts from day 5 to day 45 showed no clinical acute hepatitis (table). Molecular characterisation linked these isolates to the HEV genotype I (Burma prototype). HEV RNA was present in serum and stool samples of patients with acute hepatitis within 15 days of onset of symptoms. Evidence of viraemia and faecal shedding in symptom-free individuals without antibodies to HEV
THE LANCET • Vol 357 • January 6, 2001
could help our understanding of the diversity of host HEV infections. Although sequential samples were not available for these symptom-free contacts, the clinical follow-up did not detect an icteric phase. The inability of serological assays to detect antibodies to HEV derived from genetic variants different from the Mexico and Burmese strains could be discarded: molecular analysis has shown the Kosovar strains were linked to the Burmese strain. We suggest a potential role for symptom-free HEV carriers as a human reservoir. The detection of viraemia and faecal shedding with no antibody response have been previously reported in symptomatic patients and a few symptom-free individuals.2,3 Mainly transmitted by the faecal-oral route, person-to-person transmission of HEV is seldom considered, since only symptomatic cases are taken into account as possible sources of contamination.4 Faecal excretion is short-lived in symptomatic patients, up to 30 days after the onset of illness,1 but duration of faecal HEV shedding in symptomfree carriers should be explored. Nevertheless, the detection of HEV RNA among healthy seronegative carriers close to acute HEV cases suggests their potential role for HEV circulation during epidemics. *Elisabeth Nicand, Marc Grandadam, Remy Teyssou, Jean Loup Rey, Yves Buisson *Laboratoire de Biologie Clinique, Hôpital Val de Grâce, 75230 Paris cedex 05, France; and Service de Médecine des Collectivités, Hôpital Percy, Clamart (e-mail: [email protected]) 1
Aggarwal R, Kini D, Sofat S, Naik SR, Krawczynski K. Duration of viraemia and
Sir—N Künzli and colleagues (Sept 2, p 795)1 report on the public-health impact of outdoor air pollution, originating mainly from traffic. The calculus of new cases of chronic bronchitis or frequency of asthma attacks is straightforward and easy to interpret. I find the estimates of excess deaths and hospital admissions more difficult. To estimate the impact on mortality in the populations in Austria, France, and Switzerland, Künzli and colleagues used the results from two studies of long-term effects of air pollution.2 They derive a joint relative risk estimate of 1·043 per 10 g/m3 particulate matter (PM10) for all-cause mortality in adults—4·3% increase of mortality. The relative risk estimate was applied together with an averageexcess degree of exposure of slightly more than 20 g/m3 PM10, to the number of non-violent deaths in each population. Künzli and colleagues estimated that about 41 000 excess deaths occur per year from air pollution in these three countries. Although this way of quantifying the effect is simple and striking, I find it rather misleading. Excess deaths are deaths that occur earlier than expected. The important question is how much earlier? They approach an answer by stating that the mean age at death due to cardiopulmonary causes is higher than that for all other causes. Death from this cause might generally occur at advanced age, but we cannot infer that everyone who dies from air pollution is old. A reanalysis of the two original studies suggests that the relative risk from air pollution is uniform with age and might be somewhat higher at age 70 years and younger.2,3 Since the mechanisms of long-term and short-term effects from
69
For personal use only. Not to be reproduced without permission of The Lancet.
progestagens might have harmful orally effects on the breast,3 administered progestagens may have a detrimental effect on the breast,3 orally administered progestagens would not be acceptable to women taking tamoxifen to lower their chance of developing breast cancer. Direct administration of progestagen to the endometrium effectively protects it with little or no systemic effect. Although not licensed for this use, the use of a progestagen or levonorgestrelreleasing intrauteruine system might have protective effects against tamoxifen. If so, many women could continue with tamoxifen, rather than being deprived of the substantial benefits it offers against development of primary breast carcinoma.4 *M J Dickson, T Pandiarajan Department of Obstetrics and Gynaecology, Copeland Offices, Birch Hill Hospital, Rochdale, Lancashire OL12 9QB, UK 1
2
3
4
Bergman L, Beelen MLR, Gallee MPW, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Lancet 2000; 356: 881–87. Ismail SM. Pathology of endometrium treated with tamoxifen. J Clin Pathol 1994; 47: 827–33. Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000; 283: 485–91. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998; 90: 1371–88.
Sir—Liesbeth Bergman and colleagues1 use epidemiological data associated with endometrial cancer to rebut advocates for tamoxifen use in healthy women. Clinical neuropsychological testing is necessary before tamoxifen use in healthy women is recommended. Cognitive deficits are seen when formal neuropsychological testing is done on breast-cancer patients treated with chemotherapy plus tamoxifen or chemotherapy alone.2 Tamoxifen acts as a non-competitive block to the ligated serotonin channel in the central nervous system.3 Subtests that assess memory, executive function, visual perception, and motor dexterity should be highlighted. Visual performance with the starry night task test and motion discrimination using low and high velocity dot kinetogram might document the organic explanation for women’s visual blurring complaints while on tamoxifen. Pamela Kairies 3647 Cedarbrae Lane, San Diego, CA 92106, USA 1
68
Bergman L, Beelen MLR, Gallee MPW, et al. Risk and prognosis of endometrial
2
3
cancer after tamoxifen for breast cancer. Lancet 2000; 356: 881–87. Schagen S, van Dam F, Muller M, Boogerd W, Lindeboom J, Bruning P. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 1999; 85: 640–50. Allen M, Newland C, Valverde M, Hardy S. Inhibition of ligand-gated cation-selective channels by tamoxifen. Eur J Pharmacol 1998; 354: 261–69.
Sir—Liesbeth Bergman and colleagues1 show risk of endometrial cancer increases with increasing duration of tamoxifen use. More importantly, they show that women who develop endometrial cancer have a worse outlook, less favourable histology, higher stage, and later prescription than previously thought. Although tamoxifen has oestrogenantagonistic effects on breast-cancer cells, it has oestrogen-agonistic activity at other sites, including the endometrium and bone.2 Exposure to unopposed oestrogen increases the risk of endometrial hyperplasia and cancer, and a progestagen is generally added to hormone-replacement therapy to protect the endometrium. The oestrogen-agonistic activity of tamoxifen on the uterus mimics exposure of the endometrium to unopposed oestrogen, It would, therefore, seem sensible to investigate the use of progestagens to protect the endometrium in patients using tamoxifen. Whether progestogens exert a beneficial or harmful effect on the initiation or promotion of breast cancer seems unclear. Progestogens have been used in the treatment of metastatic breast cancer and response rates are similar to that of tamoxifen. However an observational study has suggested that combined oestrogen and progesterone hormone-replacement therapy seems to increase patients’ risks of developing breast cancer compared with oestrogen therapy alone.3 A prospective study on apes might shed more light on this dilemma, suggesting that oestrogenic activity is necessary for progestagens to have a harmful effect on the breast.4 Given the prevalence of breast cancer, it is not surprising that thousands of women in the UK are taking tamoxifen. The Breast Cancer Prevention Trial in the USA5 showed that women with an increased genetic risk of developing breast cancer had a 45% reduction in that risk if they took tamoxifen. If the results of that trial are substantiated, thousands more women will undoubtedly be keen to take tamoxifen. Physicians and patients need clear guidelines as to how best monitor and protect the endometrium from the
unwanted side-effects of tamoxifen, or both. At present, patients are encouraged to report symptoms of vaginal discharge or bleeding. For some this sign may be too late. The medical profession needs to look closely at the risks, benefits, and cost effectiveness of combining progestagens with tamoxifen. If progestagens are beneficial to these patients they may be better delivered to the endometrium locally (eg, the intrauterine levonorgestrel system) to avoid unwanted systemic side-effects. *Fiona Marsh, Martin Mayfield (e-mail: [email protected]) 1
2
3
4
5
Bergman L, Beerlen MLR, Gallee MPW, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Lancet 2000; 356: 881–87. Dixon M, Sainsbury R. Diseases of the Breast, 2nd edn. London: Churchill Livingstone: 147: 1998. Schairer C, Lubin J, Troisi R, et al. Menopausal oestrogen and oestrogenprogesterone replacement therapy and breast cancer risk. JAMA 2000; 238: 485–91. Cline JM, Soderqvist G, Von Shoultz, et al. Effects of conjugated oestrogens, medroxyprogesterone acetate and tamoxifen on the mammary glands of macaques. Breast Cancer Res Treat 1998; 48: 221–29. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel project P-1 study. J Natl Cancer Inst 1998; 90: 1371–88.
Viraemia and faecal shedding of HEV in symptom-free carriers Sir—Rakesh Aggarwal and colleagues (Sept 23, p 1081)1 report that hepatitis E virus (HEV) RNA is not detected in stool or serum samples beyond the phase of clinical course and biochemical hepatitis. They conclude that recovered patients are unlikely to serve as reservoirs in HEV-endemic areas. We provide complementary data that may clarify the potential human reservoir of HEV during epidemics. From August, 1999, to November, 1999, we investigated an outbreak of clinical acute hepatitis among Albanian Kosovar refugees returning home to Mitrovica after the withdrawal of the Serbs from Kosovo. This outbreak was spotted early because of the epidemiological and biological collaborations between the Institute of Public Health of Mitrovica and the French Military Health Service. With informed consent, we tested 103 Albanian Kosovars (age 2–50 years [mean 13·6]) and two French members of non-governmental
THE LANCET • Vol 357 • January 6, 2001
For personal use only. Not to be reproduced without permission of The Lancet.
CORRESPONDENCE
Individual’s Geographic Clinical Sex Age IgG and HEV RNA in serum* number origin characteristics (years) IgM to HEV
⫺
⫺ (3 samples collected on days 12, 21, 45) ⫺ (1 sample collected on day 8) + (1 sample collected on day 15) ⫺ (1 sample collected on day 8) ⫺
⫺ (1 sample collected on day 30) + (1 sample collected on day 15) +
⫺ ⫺ ⫺
+ ⫺ +
NA + NA
1
Kosovar
Acute hepatitis
M
46
+
2
French
Acute hepatitis
M
28
+
3
Kosovar
Acute hepatitis
F
5
⫺
4
Kosovar
Acute hepatitis
F
11
⫺
5
Kosovar (wife of index case) Kosovar Kosovar Kosovar (twin of number 7)
Symptom-free
F
42
Symptom-free Symptom-free Symptom-free
M M F
8 10 10
6 7 8
HEV RNA in stools ⫺ (1 sample collected on day 45) NA
NA=not available. *Date of collection of samples after onset of symptoms.
2
3
4
faecal viral excretion in acute hepatitis E. Lancet 2000; 356: 1081–82. Caudill JD, Malik IA, Tsarev SA. Evidence for human hepatitis E virus (HEV) infection without acute antibody response. Am J Trop Hyg 1994; 51: 201. Clayson E, Myint KS, Snitbhan E, et al. Viraemia, fecal shedding and IgM and IgG responses in patients with hepatitis E. J Infect Dis 1995; 172: 927–33. Touze A, Enogat N, Buisson Y, Coursaget P. Baculovirus expression of chimeric hepatitis B core particles with hepatitis E epitopes and their use in a hepatitis E immunoassay. J Clin Microbiol 1999; 37: 438–41.
Public health and air pollution
Epidemiological characteristics and hepatitis E markers
organisations ([NGOs] aged 28 and 30 years) who had clinical acute hepatitis for serological hepatitis markers. We also investigated 27 symptom-free individuals (age 7–41 years [mean 13·1]) who were household or school contacts of cases. Most of the acute hepatitis cases (90 of 105), including the two NGO members, and five symptom-free contacts had antibodies to hepatitis A virus. A Kosovar aged 46 years from whom we took samples on days 12, 21, and 45 after the onset of first symptoms, and one Frenchman sampled on day 8 were strongly reactive for IgG antibodies to HEV and IgM to HEV, which confirmed the diagnosis of acute hepatitis E. HEV RNA was searched by RTPCR in all serum and in stool samples (collected for a few individuals). HEV RNA was undetectable in three sequential serum samples from the Kosovar index case and in the NGO member (table). Two children with acute hepatitis had HEV RNA in one serum sample (number 3) and in a stool sample (number 4, table) taken on day 15 after the onset of first symptoms, but tested negative for IgM and IgG to HEV. Viraemia and faecal shedding were detected in four symptom-free contacts who were seronegative for HEV antibodies. The follow-up of these contacts from day 5 to day 45 showed no clinical acute hepatitis (table). Molecular characterisation linked these isolates to the HEV genotype I (Burma prototype). HEV RNA was present in serum and stool samples of patients with acute hepatitis within 15 days of onset of symptoms. Evidence of viraemia and faecal shedding in symptom-free individuals without antibodies to HEV
THE LANCET • Vol 357 • January 6, 2001
could help our understanding of the diversity of host HEV infections. Although sequential samples were not available for these symptom-free contacts, the clinical follow-up did not detect an icteric phase. The inability of serological assays to detect antibodies to HEV derived from genetic variants different from the Mexico and Burmese strains could be discarded: molecular analysis has shown the Kosovar strains were linked to the Burmese strain. We suggest a potential role for symptom-free HEV carriers as a human reservoir. The detection of viraemia and faecal shedding with no antibody response have been previously reported in symptomatic patients and a few symptom-free individuals.2,3 Mainly transmitted by the faecal-oral route, person-to-person transmission of HEV is seldom considered, since only symptomatic cases are taken into account as possible sources of contamination.4 Faecal excretion is short-lived in symptomatic patients, up to 30 days after the onset of illness,1 but duration of faecal HEV shedding in symptomfree carriers should be explored. Nevertheless, the detection of HEV RNA among healthy seronegative carriers close to acute HEV cases suggests their potential role for HEV circulation during epidemics. *Elisabeth Nicand, Marc Grandadam, Remy Teyssou, Jean Loup Rey, Yves Buisson *Laboratoire de Biologie Clinique, Hôpital Val de Grâce, 75230 Paris cedex 05, France; and Service de Médecine des Collectivités, Hôpital Percy, Clamart (e-mail: [email protected]) 1
Aggarwal R, Kini D, Sofat S, Naik SR, Krawczynski K. Duration of viraemia and
Sir—N Künzli and colleagues (Sept 2, p 795)1 report on the public-health impact of outdoor air pollution, originating mainly from traffic. The calculus of new cases of chronic bronchitis or frequency of asthma attacks is straightforward and easy to interpret. I find the estimates of excess deaths and hospital admissions more difficult. To estimate the impact on mortality in the populations in Austria, France, and Switzerland, Künzli and colleagues used the results from two studies of long-term effects of air pollution.2 They derive a joint relative risk estimate of 1·043 per 10 g/m3 particulate matter (PM10) for all-cause mortality in adults—4·3% increase of mortality. The relative risk estimate was applied together with an averageexcess degree of exposure of slightly more than 20 g/m3 PM10, to the number of non-violent deaths in each population. Künzli and colleagues estimated that about 41 000 excess deaths occur per year from air pollution in these three countries. Although this way of quantifying the effect is simple and striking, I find it rather misleading. Excess deaths are deaths that occur earlier than expected. The important question is how much earlier? They approach an answer by stating that the mean age at death due to cardiopulmonary causes is higher than that for all other causes. Death from this cause might generally occur at advanced age, but we cannot infer that everyone who dies from air pollution is old. A reanalysis of the two original studies suggests that the relative risk from air pollution is uniform with age and might be somewhat higher at age 70 years and younger.2,3 Since the mechanisms of long-term and short-term effects from
69
For personal use only. Not to be reproduced without permission of The Lancet.