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Committee on the medical effects of air pollutantsMinutes of the meeting held on Friday 18th February 2005 in Room 140B, Department of Health, Skipton House, 80 London Road, London SE1 6LH.
ITEM 1. OPENING REMARKS, APOLOGIES FOR ABSENCE AND ANNOUNCEMENTS 1. Apologies for absence were received from Prof. Philip Poole-Wilson, Mr Ben Armstrong, Prof. Dafydd Walters, Prof. Stephen Holgate, Mr Fintan Hurley, Dr Paul Harrison, Ms Alice Lambert, Prof. Tony Frew, Mr Ronnie Alexander (Welsh Assembly), Mr Nigel McMahon (Northern Ireland). 2. The Chairman welcomed Jackie Maud, Human Health Science advisor from the Environment Agency who will attend COMEAP as an observer. 3. The Chairman asked Members to declare any interests on the item to be discussed at today's meeting. No interests were declared. 4. The Chairman reminded Members to submit their expenses claims forms. Blank forms had been tabled. ITEM 2. MINUTES OF THE MEETING HELD ON 26th November 2004 5. The Chairman took Members through the Minutes of the last meeting page by page. Two changes were requested:
Action: Secretariat 6. Members agreed that once the above-mentioned changes had been made, the minutes were agreed as an accurate record of the meeting. ITEM 3. MATTERS ARISING Annual Air Pollution Meeting - Leicester 7. Members were informed that the Secretariat for this meeting had not been overwhelmed by applications and were reminded that they were obliged to attend the 3rd and 4th day of this meeting. 8. One Member reminded the Committee that this meeting fell back to back with the HEI annual meeting in Boston, an event to which he had alerted the Secretariat prior to dates for the meeting in Leicester being confirmed. Experts attending the HEI meeting might be unwilling to attend both meetings, so contributing to the reduction in applicant numbers. 9. Another member informed the Committee that the NSCA spring workshop (21-22 April 05) also clashed with the meeting in Leicester which may also have contributed to the reduction in applicant numbers. ITEM 4: CARDIOVASCULAR DISEASE AND AIR POLLUTION REPORT COMEAP/2005/1 Overview 10. The Chairman informed Members that a substantial amount of work had been carried out on the report since the last meeting, although the occupational section had still to be completed. 11. The Chairman stated that once Members' comments from this meeting had been incorporated, and Members had approved a copy for comment, the report would be published on the web for general comments for six weeks. Following final amendments, the report would be published on the web and a limited number of hard copies printed for Members and the sub-group. 12. Figures and tables had now been included and the appendices completed. 13. The Chairman confirmed that a presentation of the main topics within the report would be presented at the British Cardiac Society's annual scientific meeting in late May 2005. 14. Only the more substantial amendments discussed are mentioned below. General Comments 15. It was felt there was variation in the depth of detail between Chapters 1 and 2 and Chapters 3 and 4, the latter of which presented more of an overview. It was also noted that Chapters 1 and 2 covered all pollutants, but 3 and 4 focussed mainly on particles. It was agreed that an explanation of this unevenness was required in the introduction. Action: Secretariat 16. Written comments had been received from absent Members of both the Committee and the sub-group. It was confirmed that major comments would be discussed at this meeting so that all could comment on the issues raised. The comments would then be incorporated into the report as appropriate. Executive Summary 17. It was noted that it was important for there to be no contradiction between what was stated in this section and other sections of the report, in particular the conclusions chapter. Action: Secretariat Chapter 1 Introduction 18. Paragraph 1.2 was discussed. The paragraph described the London smog of 1952 and commented that the final death toll may have significantly exceeded 4000 due to the persistence of health effects from the smog. It was felt that this wording could be altered to emphasise the point that this was recognised at the time. Action: Prof. Anderson 19. Sections 2.1 - 2.4 were discussed. Members noted that the studies considered fell into two main sections, temporal and spatial and it was agreed that it would be better to organise the section around these two divisions and to rearrange the sections in this way. Action: Secretariat 20. It was noted that the number of forest plots provided in the report was helpful, as was the explanatory diagram on page 62. 21. Members discussed the definition of "combined estimate" and it was highlighted that there was a lack of consistency in the use of some terminology throughout the report. For example, the diagram on page 62 used 'result of random effects model', page 63 line 198 used 'random effects meta-analytic estimate' and page 64 line 22 used 'combined estimate'. Some members preferred "summary estimate". It was agreed that the Secretariat would standardise the use of such terminology throughout the report. Action: Secretariat 22. Paragraph 2.47, page 65 was discussed. It was agreed to change the sentence "The consistency of positive associations is remarkable.." to read "The vast majority of these studies have produced positive associations..". Action: Secretariat 23. There was some debate over the title of the section before paragraph 2.98. Two members agreed to providing a title which would be passed to the Secretariat. Action: Members 24. Paragraph 2.104 was discussed. It was felt that there were too few studies on myocardial infarction and ventricular arrhythmia to enable firm conclusions to be drawn, although it was pointed out that the panel studies and case-crossover studies described had less statistical power than the time series studies. Paragraph 2.106 did not currently take the conclusions from paragraph 2.104 into account. Action: Secretariat 25. There followed some discussion about the use of the word "convincing" (first used in paragraph 2.106) and the need to make clear what Members meant through the use of this word. In the context of the report, "convincing" did not just refer to statistical significance but also to consistency across studies in different areas. The Secretariat agreed to highlight this interpretation of the word 'convincing' early on in the report. Action: Secretariat 26. The recent paper on traffic and the onset of myocardial infarction (Peters et al) was discussed. It was agreed that this paper would not be included within the report, as it did not specifically mention air pollution. 27. Members discussed the fact that PM10 associations were not very robust when NO2 was included in the model and also the theory that NO2 was a better indicator for fresh traffic exhaust than PM10. Members pointed out that the latter point was not made clear in paragraph 2.106. It was agreed that the role of this chapter was to describe associations and that interpretation of these associations came later in the report. It was agreed to refer to the later discussion on page 258 paragraph 5.11 which made this point. Action: Secretariat 28. There then followed some discussion over whether NOx was a better marker of traffic fumes than NO2. The chapter author stated that there were too few studies available to enable a confident conclusion to be drawn. This was compounded by the fact that NO2 was believed to be the more active pollutant. Members did agree that as an indicator, NOx was better and that studies on this pollutant should be included in the research recommendations. Action: Secretariat 29. The heterogeneity p values used in table 10 on page 111 were discussed and their interpretation clarified. It was agreed that a footnote to the table was required to explain the heterogeneity p values column. Action: Secretariat Effects of long-term exposure 30. Members discussed the fact that the cohort studies measured relatively recent air pollutant concentrations but the population of the cities would have experienced higher pollutant concentrations in the past. This could result in greater mortality from the higher past pollutant concentrations in the most polluted cities being allocated to the smaller, more recent range of pollutant concentrations. Thus, the coefficient could be overestimated as illustrated in the figure in the report on page 152. 31. It was noted that it was also possible that the coefficient could
be underestimated due to measurement error. In addition, the composition
of the pollution mixture had changed over time, which might over or underestimate
the coefficient. It was noted that these issues were less important if
there was a relatively short lag between exposure and the change in mortality
as was suggested by the study in Dublin. It was agreed that paragraph
2.168 or 2.169 would be amended to take these points into account. It
was also agreed to add an indication of the length of the timescale and
to widen the difference between the two lines in the figure. Action: Secretariat 32. The recent study in Los Angeles was discussed. This was important because it suggested that the associations found in the ACS study were not an artefact of unknown differences between cities. This was because the Los Angeles study found the same associations within an urban area rather than across cities. It was agreed that text making this point would be provided for the report. It was also noted that the pollution mixture was dominated by traffic pollution in Los Angeles, a situation which differed from the change in coal smoke pollution studied in Dublin and the change in sulphur dioxide and sulphate studied in Hong Kong. Action: Prof. Anderson 33. It was noted that there was a positive association between long-term exposure to coarse particles and mortality. Although this association was not statistically significant, this association should be remembered as it might be confirmed by further studies in the future. It was agreed to add some text on coarse particles. Action: Secretariat 34. Regarding the section on lead and blood pressure, the Committee commented that lead in air made a relatively minor contribution to blood lead levels, compared with other sources of lead exposure. 35. It was emphasised that the Hong Kong study was not just about particles but that there had been a drop in sulphur dioxide as well as in sulphate particles. It was agreed to amend paragraph 2.205 accordingly to make this clear. There was also discussion of whether the change to low sulphur fuel in Hong Kong could change the composition of the particles emitted. 36. It was noted that the evidence on the effects of long term exposure was convincing for different reasons to those regarding the evidence on short term exposure. There was one study with a large number of cities which had been subject to exhaustive analysis with adjustment for many risk factors. There were also a few smaller studies. It was agreed that paragraph 2.206 would be amended to make this clear. 37. There was discussion of the degree to which the results from the
US cohort studies were transferable to Europe. It was agreed to make clear
that the text in paragraph 2.206 refer to studies in the US and to expand
the discussion of transferability in paragraph 2.207. Chapter 3: Potential mechanisms underlying the cardiovascular effects of air pollutants. Introduction and the clotting hypothesis 38. The Secretariat introduced this chapter, informing Members that the reference section had still to be completed and that diagrams and illustrations which had been referenced in the text had yet to be incorporated. 39. At the last meeting of COMEAP, the Secretariat reminded Members that
it had been suggested that the term 'clot' should be replaced with the
term 'thrombus'. However, after some consideration, it had been decided
that the word 'clot' read more easily and was satisfactory. 41. One Member reiterated a comment stated earlier in the meeting which noted that the style of this chapter differed from the previous chapter and read more like a review and that it focussed more heavily on particles. Once it was explained that this was due to the majority of data relating to particulates, it was suggested that it would therefore be useful to add an introduction or a lay summary to this chapter providing an explanation of why the style differed and why there was an emphasis on particles. Action: Secretariat 42. It was noted that a conclusions section to this chapter had been omitted, although conclusions from this chapter had been provided in the Discussion, Conclusions and Recommendations chapter. It was agreed that this would be added. Action: Secretariat 43. It was noted that the sentence in paragraph 3.30, (particles which appeared to be associated with cardiac effects were composed largely of carbon, ammonium sulphate and nitrate) was ambiguous. The epidemiological chapter only described evidence on PM2.5, not its constituents. It was suggested that it was made clear that it was PM2.5 which was associated with cardiac effects. A detailed study of particle composition and cardiac effects had not been undertaken. Members suggested that a note should be added about the importance of the surface area of particles and an alternative phrase found for the term 'simple chemistry'. Action: Secretariat 44. It was agreed that figure 32 would be re-drawn and sent to the Secretariat for inclusion at the end of both this chapter and chapter 4. Action: Dr Stone & Prof. Donaldson 45. It was noted in paragraph 3.50 that the possible link between the destabilisation of atheromatous plaques and ozone should be removed (this referred to endogenous ozone production). Action: Secretariat 46. It was noted that the section on human studies starting on page 201 did not contain any description of chamber studies. It was pointed out that most of these were on respiratory rather than cardiovascular endpoints. There were some chamber studies on carbon monoxide and angina. It was agreed to add text on these. Action: Secretariat Chapter 4 - Potential mechanisms underlying the cardiovascular effects of air pollutants : the neural hypothesis 47. A member asked whether it was possible to say which particular pollutants were involved in causing changes in HRV and that, if a variety of pollutants were involved, whether it would be sensible to label the top of Figure 32 'Air Pollutants'. Members were informed that sulphur dioxide did have an effect, as did particles, although sulphuric acid did not. The Chairman informed the Committee that challenge studies had not been carried out for effects on HRV using NO2, O3, or CO. CO had been studied for the onset of angina and ST segment changes. Action: Dr Stone & Prof. Donaldson 48. It was also requested that an explanatory paragraph be added on how NF-?B works. Action: Dr Stone 49. In the summary section of this chapter, it was noted that it was hard to actually prove mechanisms in toxicology and that the wording in paragraph 4.34 should be changed to 'a crucial piece of evidence lacking'. Action: Secretariat 50. A query was raised about whether the reference to the Peters et al 2000 study in paragraph 4.17 correctly matched the discussion in the text on the Boston ICD pilot study. It was agreed that the reference would be checked and changed if necessary. It was also agreed that 'strong evidence' would be amended to 'some evidence' in the 5th line. Action: Secretariat Chapter 5 - Discussion, conclusions and recommendations 51. Chapter 5 was renamed Discussion, Conclusions and Recommendations. 52. Members were asked to read this chapter closely as it had been carefully re-drafted in light of Members' recommendations. 53. It was proposed that 'and is increasing' was deleted from the end of the first sentence in paragraph 5.2. It was also requested that 'impaired blood flow to the heart' be amended to 'impaired blood flow to the heart muscle'. It was thought that a diagram of the heart and its circulation would be helpful. 54. It was suggested that 'coronary heart disease' was amended to 'cardiovascular
disease' in paragraph 5.3 and that the paragraph was split into two sentences
at the dash. There was discussion of the relative amounts of time-series
evidence on cardiovascular disease and on coronary heart disease. It was
noted that the evidence from time series studies on stroke was rather
unclear. It was pointed out that, since patients could die of stroke some
time after first being admitted to hospital, time series studies using
a lag of only a day or two might miss an effect. It was agreed to rewrite
these paragraphs to take these points into account. Action: Secretariat 55. It was agreed to split paragraph 5.5 into more than one paragraph. It was also pointed out that the current text might be taken to imply that clotting of the blood led to instability of atherosclerotic plaques. In fact, instability of atherosclerotic plaques could lead to clotting, although clotting could occur independently as well. In the 7th line 'humoral factors' was suggested as an alternative to 'biochemical factors' and it was noted that these factors could come from the liver not just from the pulmonary epithelium. It was agreed that this paragraph would be rewritten accordingly. Action: Dr Stone 56. 'Convincing' evidence was considered to result from statistically significant associations, from consistency across studies and from a public health impact of reasonable magnitude. It was suggested that the terms 'convincing' and 'important' should be used in paragraph 5.7, deleting 'and convincing' from the end of the sentence. In addition, the last sentence of paragraph 5.8 would be amended to 'A number of questions need addressing.' And paragraph 5.9a) would refer to 'a formal meta-analysis'. Action: Secretariat 57. Paragraph 5.9b) would be rewritten to incorporate more comments on transferability from the US to Europe and to refer to COMEAP's 2001 report. It was suggested that the first line of 5.9c) would be amended to 'generally refer to a 10 µg/m3 change' (carbon monoxide associations referred to a 10 mg/m3 change). It was also queried whether black smoke levels were as high as 10,000 µg/m3 in the 1952 smog. It was explained that the filters became overloaded but this point would be checked. A '+' would be added to Table 25 against cardiac admissions and black smoke. Action: Secretariat 58. There was some discussion of specificity as one of the contributing guidelines for judging causality. It was agreed to amend the start of the paragraph on specificity on page 251 to 'Specificity is often taken…' Action: Secretariat 59. There was also some discussion of two pollutant models. It was proposed that the sentence in paragraph 5.11 starting 'It was noted…' should be deleted and that the last part of the paragraph would be redrafted. It was suggested that the redrafting of the last part of the paragraph should include a reference to the fact that some indication of the importance of different pollutants could be gained from studies of the heterogeneity of time series coefficients across different geographical locations. Other pollutants could be examined as possible effect modifiers contributing to this heterogeneity. Action: Mr Armstrong 60. It was agreed to look at all of the paragraphs 5.12 (i), (ii), (iii) in terms of the balance between evidence on particles and evidence on gaseous pollutants. It was suggested that a table be produced providing a qualitative overview of the evidence across the various types of studies in the report for both particle metrics and gaseous pollutants. Action: Secretariat 61. Members suggested that the text at the end of paragraph 5.15 should be amended to make clear that the annual average figure of 18 µg/m3 referred to London (levels in the UK were about 7-10 µg/m3). Action: Secretariat 62. There was a long discussion about the section on advice to patients. It was agreed in the end to make some minor changes and then circulate with a letter to Members seeking their further views. Members were also asked to check the Executive Summary was in line with the Conclusions chapter and to write in with suggestions for research recommendations. Action: Secretariat, Members Appendices 63. It was agreed that further information on the two pollutant estimates would be included in the appropriate appendix. Action: Prof. Anderson Secretariat
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