Dear Editor

Just a casual letter from a layman here, but it would seem clear that the NOx higher levels correlating with higher lung cancer would be as a result simply of higher exposure to diesel exhaust. Looking on the Web I see worker exposure studies to older diesels show higher lung cancer rates as well. When I was in Norway visiting my wife's relatives in 1992 I was stunned by the unhealthy stench of diesel even in Bergen in places. The US, which has its own air pollution problems of course, managed through sheer luck to avoid having many diesel autos due to cheap gas and some poorly designed diesel engines which soured the US auto buyers on diesels. Perhaps Norway should tax diesel fuel at higher rate than gasoline rather than a lower rate as it does now. I would guess the health cost and human suffering from the air pollution per mile driven is higher with diesel but the fuels are currently taxed per liter used. Someday I hope to sit by the fountain in beautiful Bergen and smell only the flowers and the fountain, not diesel exhaust.

Dear Editor

The reproducibility of FEV1 and FVC and their respective agreement with a gold standard is an issue for early diagnosis and follow-up of COPD patients in general practice.[1] Schermer et al. performed a within subject comparison of FEV1 and FVC measured in 388 COPD-patients with a turbine flow spirometer.[2] The values of FEV1 and FVC measured by general practice personnel were compared with the values measured by certified laboratory personnel, using the same type of turbine spirometer, as the reference test. In spite of equivalent reproducibility the agreement between measurement of lung function in general practices and in laboratories was limited. Training of general practice staff is thought to be the key for valid spirometric measurements. From a primary care practice point of view three questions remain.

Firstly, the validity of FVC measured with a turbine spirometer compared with the real life gold standard of an FVC measured with a pneumotachometer, that is currently used in the lung function laboratory, might be questioned. Godschalk et al. found that underestimation of FVC measured with a turbine spirometer was much more excessive than the underestimation of FEV1 when compared with the respective outcomes of FVC and FEV1, measured with a pneumotachometer.[3] Inertia of the turbine spirometer explains the inaccuracy of the measurements in the very low flows at the end of the forced expiratory manoeuvre when the FVC is completed. Schermers’ choice for a ‘fairer’ comparison conceals the technical imperfection of the turbine spirometer compared with the gold standard of the pneumotachometer in the lung function laboratory. Unfortunately, flow volume curves made with turbine spirometers do not show this error and may therefore lead to wrong assumptions by the physician who uses a turbine spirometer. Systematic underestimation of FVC in primary care patients might result from the study as presented by Schermer et al. Do the authors agree with that?

Secondly, turbine spirometers are available for use in primary care settings, without and with ‘built in prompts’, ‘real time flow volume curves’, ‘patient instructions’ and ‘time indicators to monitor duration of expiratory flow’ as the authors state. However, sophisticated turbine spirometers seem to be in itself a barrier for their widespread use for measuring FEV1 and FVC in primary care patients.[4] On the other hand, most common faults can be detected by observation of the well-instructed patient during his forced expiratory manoeuvre, rather than by an observer who concentrates on the flow volume curves only. In spite of the use of the flow volume curves by the general practice personnel in the study of Schermer et al. the results of FEV1 and FVC were not estimated interchangeable with the results of the laboratories, although measured with the same type of turbine spirometer. Based on the study of Schermer et al. the flow volume loop would appear be too sophisticated for the primary care setting. Therefore it would be better to encourage GPs to measure lung function in their practices, straightforward with a simple handheld spirometer. Wouldn’t it?

Thirdly, in COPD the patients’ own base-line values provide the best reference data.[5] The study of Schermer et al. might underpin the relevance of frequent measurement of FEV1 and FVC. In order to promote lung function testing in primary medical care, could Schermer et al. provide us with some more detailed data on the limits of agreement of FEV1 and FVC measured by the practices and the lung function laboratories?

References

(1) Buist AS. Guidelines for the management of chronic obstructive pulmonary disease. Respir Med. 2002;96:S11-6.

(2) Schermer TR, Jacobs JE, Chavannes NH, Hartman J, Folgering HT, Bottema BJ, van Weel C. Validity of spirometric testing in a general practice population of patients with chronic obstructive pulmonary disease (COPD). Thorax. 2003;58:861-6.

(3) Godschalk I, Brackel JCK, Peters JCK, Bogaard JM. Assessment of accuracy and applicability of a portable electronic diary card spirometer for asthma treatment. Respir Med 1996;90:619-22.

(4) Ferguson GT, Enright PL, Buist SA, Higgins MW. Office spirometry for lung health assessment in adults: a consensus statement from the national lung health education program. Chest 2000;117:1146-61.

(5) Crapo RO. Pulmonary-Function Testing. N Eng J Med 1994;331:25-30.

Dear Editor

We read with interest the guidelines for the management of suspected acute pulmonary embolism by the British Thoracic Society.[1] However, we were somewhat concerned about the recommendation of administering a 50mg intravenous bolus of alteplase for the treatment of patients with massive PE [grade C recommendation]. We believe that this recommendation is misleading as this advice is based on a case series of just 6 patients, of whom 2 died.[2] There is also a paucity of data on the safety and efficacy of bolus dose alteplase compared to placebo and to other thrombolytic regimens.

There are only two small studies comparing bolus dose and standard infusions of alteplase,[3,4] neither of which were large enough to detect any significant difference in terms of thrombolytic efficacy or safety. There was, however, a slightly higher all cause mortality rate and death due to recurrent PE and major bleeding episodes in the bolus dose group in one study.[3]

We have reviewed the data on the safety and efficacy of bolus dose alteplase in comparison to standard alteplase infusions and have produced some worrying data on thrombolytic efficacy, safety and the Number Needed to Harm (NNH) if bolus dose alteplase is used in preference to standard infusions.

Standard alteplase infusions produce a statistically significantly greater rate of objectively measured thrombolysis compared to bolus dose regimens (67% of patients vs. 33% respectively, p=0.0007) corresponding to a NNH = 3 if practice was changed according to the BTS guidance. The resultant death rate due to the initial PE is consequently greater in patients receiving bolus dose alteplase (3.2% vs. 0.5%, p=0.01), equivalent to a NNH = 37. Bolus dose alteplase is also associated with a trend towards statistically significantly greater all cause mortality, deaths due to major bleeding events and recurrent PE and also a worse side effect profile (major bleeding episodes and recurrent PE).

The implications for practice from our review are that on the current available evidence, standard alteplase infusions are more effective and safer than bolus dose regimens. Thrombolytic treatment of massive PEs should continue to utilise the licensed alteplase infusion regimen rather than the bolus dose method recommended in the recent BTS guidance.

References

(1) British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003; 58: 470-484.

(2) Ruiz-Bailén M, Aguayo-de-Hoyos E, Seerano-Corcoles MC, et al. Thrombolysis with recombinant tissue plasminogen activator during cardiopulmonary resuscitation in fulminant pulmonary embolism: A case series. Resuscitation. 2001; 51: 97-101.

(3) Goldhaber SZ, Agnelli G, Levine MN, on behalf of the Bolus Alteplase Pulmonary Embolism Group. Reduced dose bolus alteplase versus conventional alteplase infusion for pulmonary embolism thrombolysis: An international multicenter randomized trial. Chest. 1994; 106: 718-724.

(4) Sors H, Pacouret G, Azarian R, et al. Hemodynamic effects of bolus versus 2-hr infusion of alteplase in acute massive pulmonary embolism: A randomized controlled multicenter trial. Chest. 1994; 106: 712-717.

Dear Editor

We thank Dodd et al. for their letter that reflects the concerns of many clinicians that short burst oxygen must be beneficial to patients if only we could prove it. Unfortunately the evidence collected to date for short bust therapy does not support this hope and since our own publication [1] a further very similar study has reached the same conclusion.[2]

In answer to the specific points raised in this letter we reassert that the conclusion of the study accurately reflects the results in which it is stated that "we found no increase in mean walk distance after oxygen and no improvement in mean breathlessness scores or recovery times with oxygen taken either before or after exercise" (abstract) and
"Oxygen during recovery. The two walks performed by each subject in this study were comparable; there was no significant difference between the mean distances walked degree of breathlessness or arterial oxygen saturation at the end of the walks" (results). In the discussion we state:
"The outcomes of both parts of this study are clear. At rates available from domiciliary systems in the UK, neither pre-breathing oxygen before exercise nor breathing oxygen during recovery was effective in relieving dyspnoea or usefully increasing submaximal exercise tolerance in COPD patients with exercise limitation and desaturation on air". We conclude;
"In summary. Our studies do not support a useful therapeutic role for domiciliary oxygen by cylinder in COPD patients who desaturate on exercise, whether it is used before or after exercise. We suggest that current prescribing practice for this therapy in the UK be revised. If the evidence from this and previous studies is to be followed, only patients with a demonstrable objective benefit should be considered suitable for such therapy".

The argument that 28% oxygen with a flow rate of 4 litres per minute may have reduced alveolar oxygen tensions and hence increased the work of breathing is negated by the increased arterial oxygen saturations observed in the subjects who were administered oxygen. We agree that the conclusion of this study is ’the practice of prescribing 28% oxygen at 4 litres to relieve dyspnoea following exercise is inappropriate without careful assessment’ and state in our own conclusions ‘domiciliary oxygen should in future only be prescribed for such patients if they have shown objective evidence of benefit on exercise testing’. The suggestion that such patients would benefit from higher flow rates delivered from new lightweight cylinders now appearing in the UK market is an interesting one but at present is just speculation and we could not deduce such a conclusion from the results of our study. We are sure that further research in this area will be conducted.

References

(1) Nandi K, Smith AA, Crawford A et al. Thorax 2003;58:670-3.

(2) Lewis CA, Eaton TE, Young P, Kolbe J. Eur Respir J 2003;2:584-8.