Asthma exacerbations

Asthma exacerbations Sir—Helen Reddel and colleagues (Jan 30, p 364)1 report of the differences in diurnal variability of peak expiratory flow (PEF) between poor asthma control and exacerbations while on inhaled corticosteroids, raises questions about the type of inflammation present on the two occasions. This question was not examined in the study, but it is relevant to the interpretation of the results. Studies of induced sputum for inflammatory indices indicate that there are different types of airway inflammation. So a reasonable assumption would be that when there was poor asthma control, the inflammation was eosinophilic because it responded to corticosteroid treatment. Exacerbations can also be eosinophilic2 and associated with increased diurnal PEF variability,3 but in the study by Reddel the exacerbations might have been different and non-eosinophilic. These exacerbations were preceded by symptoms of respiratory infection and were judged to be of viral cause, however, the pathogens were not identified. In Pizzichini and colleagues’ study of confirmed natural viral infections,4 exacerbations of asthma were associated with an absolute sputum neutrophilia without an increase in the proportion of eosinophils. Hence, the exacerbations in Reddel’s study may have been the same. A striking difference between eosinophilic exacerbations of asthma and viral exacerbations is the presence of a substantial increase in fibrinogen in the latter which may be associated with oedema.2,4 Airway oedema and the effects of such mediators as histamine and leukotrienes on ␤2-receptor function5 may differ in the different types of inflammation and may be responsible for the difference in diurnal variability of PEF. To interpret mechanisms of clinical abnormalities and the effects of treatment, it will be necessary in future to measure indices of airway inflammation, for example, by use of induced sputum. *K Parameswaran, G S Berlyne, F E Hargreave Asthma Research Group, St Joseph’s Hospital and McMaster University, Hamilton, ON, Canada L8N 4A6 1

Reddel H, Ware S, Marks G, Salome C, Jenkins C, Woolcock A. Differences between asthma exacerbations and poor asthma control. Lancet 1999; 353: 361–69. 2 Pizzichini MMM, Pizzichini E, Clelland L, et al. Sputum in severe exacerbations of

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asthma: kinetics of inflammatory indices after prednisone treatment. Am J Respir Crit Care Med 1997; 155: 1501–08. 3 Gibson PG, Wong BJ, Hepperle MJE, et al. A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid. Clin Exp Allergy 1992; 22: 525–32. 4 Pizzichini MMM, Pizzichini E, Efthimiadis A, et al. Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility study. Am J Respir Crit Care Med 1998; 158: 1178–84. 5 Sauz ML, de la Cuesta CG, Oehling A. Modulation of ␤2 adrenoreceptors in human lymphocytes by in-vitro stimulation with mediators. J Invest Allergol Clin Immunol 1994; 4: 116–21.

Comparison of radiation side-effects in prostate cancer Sir—David Dearnaley and colleagues (Jan 23, p 267)1 report significantly reduced late rectal toxicity after conformal radiotherapy in patients with prostate cancer. The investigators concluded that dose escalation of external beam irradiation of the prostate is feasible, and a randomised phase III trial is planned to test this hypothesis. However, some caution is warranted. The Radiation Therapy and Oncology Group (RTOG) system is based on physicians’ assessment of subjective morbidity. Quality-of-life research has clearly shown that substantial discrepancies exist between patient-perceived and physician-reported subjective sideeffects.2,3 Conformal radiotherapy of prostate cancer probably reduces proctitis symptoms of minor to moderate severity assessed by the RTOG compared with conventional radiotherapy. Nevertheless, patients should be told about the risk of rectal bleeding and mucus discharge, even though modern radiotherapy techniques are applied. This risk is particularly real if large extraprostatic tumours are irradiated. In such a case, radiation fields include all or part of the seminal vesicles. Consequently, organs at risk, such as bladder and rectum, will partly be included in the target volume. However, these structures can be shielded by blocks or simply by reducing the margins of the target volume. High-dose irradiation of the prostate gland will always include parts of the anterior rectal wall. Clinical data from our hospital show that moderate, patient-perceived late rectal side-effects are less dependent on the irradiated volume than more severe endpoints,1 and can best be

predicted by high-dose measures of the dose-volume histogram. This finding accords with the finding of Dearnaley and colleagues 2 in which no significant difference in rectal pain (grade I) was seen between the conventional and the conformal groups, whereas a significant reduction in rectal bleeding (grade II) was obtained after conformal irradiation compared with conventional treatment. If these findings of patient-perceived late sideeffects are confirmed, only moderate dose escalation may be feasible with conformal radiotherapy. Radical radiotherapy can be regarded as a curative treatment option for patients with prostate cancer. Treatment-related morbidity should be avoided. We share the concern that rectal bleeding and other late adverse toxic effects will allow only cautious increase of dose to the rectum. *Wolfgang Lilleby, Dag Rune Olsen, Sophie D Fosså Norwegian Radium Hospital, Department of Oncology and Radiotherapy, N-0310 Oslo, Norway 1

Dearnaley D, Khoo VS, Norman AR, et al. Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. Lancet 1999; 3 5 3 : 267–72. 2 Watkins-Bruner D, Scott C, Lawton C, et al. RTOG’s first quality of life study: RTOG 90–20. Int J Radiat Oncol Biol Phys 1995; 1 1 : 901–06. 3 Lilleby W, Fosså SD. Long-term morbidity and quality of life in patients with localised prostate cancer undergoing definitive radiotherapy or radical prostatectomy. Int J Radiat Oncol Biol Phys (in press). 4 Dale E, Olsen DR, Fosså SD. Normal tissue complication probabilities correlated with the late effects in the rectum after prostate conformal radiotherapy. Int J Radiat Oncol Biol Phys 1999; 43: 385–91.

Xenotransplantation deserves better Sir—In his Feb 6 news item (p 476),1 Denis Durand de Bousingen reports that the parliamentary assembly of the Council of Europe supports the idea of a worldwide moratorium on animal transplants. The proposal was made by the French geneticist and member of parliament Jean-François Mattei, and was based on a memorandum drafted by Swiss physicist Gian-Reto Plattner,2 who was absent from the proceedings. Plattner emphasised the unacceptibility of the risk of transmission of animal viruses to man. However, the main arguments of the report discussed by the assembly hinged on the following dubious statements.

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