- Email: [email protected]
Fluticasone and asthma
CORRESPONDENCE
biopsy underwent treatment with interferon alfa-2b (3 MU three times weekly) plus ribavirin (1 g daily) for 12 months. Before the start of treatment, she had no diarrhoea and no biological signs of malabsorption. After 1 month of treatment, the patient started to develop diarrhoea, which persisted under symptomatic treatment. After 2 months of treatment, we admitted her to hospital because of persisting diarrhoea, hypokalaemia, and weight loss. Serum alanine aminotransferase was normal and HCV RNA was negative on RT-PCR. Ribavarin was maintained and interferon alpha-2b was stopped. Upper-gastrointestinal endoscopy showed a flat duodenal mucosa. Distal duodenal histology resulted in total villous atrophy. Positive antibodies to endomysium and the response to gluten-free diet enabled us to make a diagnosis of coeliac disease. The archival serum samples obtained before interferon and ribavarin treatment were positive for antibodies to endomysium. 10 days after she started a gluten-free diet, diarrhoea disappeared, the patient gained weight, and hydroelectroytic disorders were corrected, and we were able to renew interferon treatment. In September, 1997, we assessed a woman aged 31 years with coeliac disease for antiendomysium positivity, total villous atrophy on distal duodenal histology, and healing of intestinal architecture after 1 year of gluten withdrawal, underwent 1 year of treatment with interferon alfa-2b (3 MU three times weekly) for chronic active hepatitis C on liver biopsy. No effects from interferon were seen with the gluten-free diet. The patient was non-responder and from November, 1999, to October, 2000, she underwent a second treatment with interferon alpha-2b (6 MU three times weekly for 24 weeks, then 3 MU three times weekly for 24 weeks) plus ribavarin 1 g daily. Again, she had no adverse effects. We agree with Cammarota and colleagues that patients with chronic hepatitis C must be screened for endomysium before interferon treatment given the high prevalence of the disease in the general population (one per 200).3 Interferon treatment is possible in conjunction with a strict gluten-free diet. *Marc Bourlière, Valérie Oulés, Hervé Perrier, Cécile Mengotti Department of Hepato-Gastroenterology, Hôpital Saint Joseph, 13008, Marseille, France (e-mail: [email protected])
804
1
2
3
Cammarota G, Cuoco L, Cianci R, Pandolfi F, Gasbarrini G. Onset of coeliac disease during treatment with interferon for chronic hepatitis C. Lancet 2000; 356: 1494–95. Bardella MT, Marino R, Meroni PL. Celiac disease during interferon treatment. Ann Intern Med 1999; 131: 157–58. Maki M, Collin P. Coeliac disease. Lancet 1977; 349: 1755–59
Fluticasone and asthma Sir—We would like to comment on the statement made by Woodstock and colleagues (Nov 11, p 1682).1 They claim that the determination of volume of distribution in a study by Thorsson and colleagues2 is incorrect. Woodstock and colleagues’ reasoning is based on the low dose used by those investigators, which does not permit adequate detection. The statement is not, however, valid, since Thorsson and colleagues used tritiumlabelled compound, which increased assay sensitivity seven-fold compared with the assay used in the study by Martin Brutsche and colleagues3 of inhaled fluticasone propionate in patients with asthma and healthy volunteers, on which Woodstock and colleagues comment. The two assays allowed accurate measurement of fluticasone in plasma for 10–12 h. Surprisingly, Brutsche and colleagues did not take full advantage of their use of the high dose of fluticasone, which, according to our estimates, would allow measurement of the half-life of the drug from samples up to 48 h. In Thorsson and colleagues’ and Brutsche and colleagues’ studies sampling was stopped at 12 h, which is a shortcoming of each because of possible underestimation of half-life and inaccurate measurement of volume of distribution. To overcome this inadequate estimation, single dose inhalation data, with plasma concentrations for up to 48 h, were fitted simultaneously with the intravenous data to a model that gave a more reliable estimate of the half-life and the volume of distribution in the study by Thorsson and colleagues. The long half-life, the large volume of distribution, and the plasma accumulation of fluticasone seen with repeated dosing are indeed atypical when compared with other inhaled corticosteroids, and are most likely related to the high lipophilicity of the drug. Staffan Edsbäcker, Lars Thorsson Experimental Medicine, AstraZeneca R&D Lund, s-221 87 Lund, Sweden (e-mail: [email protected])
1
2
3
Woodcock A, Daley-Yates PT. Fluticasone propionate bioavailability in asthma. Lancet 2000; 356: 1682. Thorsson L, Dahlström K, Edsbäcker S, Kallén A, Paulson J, Wirén J-E. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1997; 43: 155–61. Brutsche MH, Brutsche IC, Munawar M, et al. Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study. Lancet 2000; 356: 556–61.
Discomfort with fineneedle aspiration cytology of the breast Sir—In their Nov 18 Commentary, Sutini Ngadiman1 and colleagues discuss keeping to a minimum discomfort during fine-needle aspiration (FNA) cytology of the breast. As they comment, I Daltrey and colleagues2 report use of blue-hub 23G needles without local anaesthesia as the choice for breast FNA. Bluehub needles give as good a cytological yield as a 21G needle.3 In our practice, we found that infiltration of local anaesthetic lateral to the incision site provided effective postoperative analgesia after surgical excision of breast lumps (unpublished data). We therefore did a prospective study to investigate whether a similar technique of anaesthetic infiltration lateral to the breast lump before FNA decreased pain scores. We studied 50 consecutive patients who underwent two diagnostic FNAs as part of investigation of benign breast lumps to assess degree of pain experienced and quality of prepared smears, with and without local anaesthesia. Our practice has a surgeon and cytopathologist in attendance at each breast clinic, and the cytopathologist (NA) does all aspirations. FNAs were done without local anaesthesia on the first visit. On the second visit, 5 mL 0·5% bupivocaine was injected lateral to the breast lump and FNA was done 20–30 min later. The patients were instructed to score the pain experienced at the first FNA as 10 on a horizontal linear visual analogue scale ranging from 0 to 10, and each patient scored the second procedure relative to that score. 43 (86%) of 50 patients had significantly improved pain scores: median pain score 3 (range 0–10). The quality of the FNA smears prepared was the same, with and without local anaesthetic. The beneficial action of local
THE LANCET • Vol 357 • March 10, 2001
For personal use only. Reproduce with permission from The Lancet Publishing Group.
biopsy underwent treatment with interferon alfa-2b (3 MU three times weekly) plus ribavirin (1 g daily) for 12 months. Before the start of treatment, she had no diarrhoea and no biological signs of malabsorption. After 1 month of treatment, the patient started to develop diarrhoea, which persisted under symptomatic treatment. After 2 months of treatment, we admitted her to hospital because of persisting diarrhoea, hypokalaemia, and weight loss. Serum alanine aminotransferase was normal and HCV RNA was negative on RT-PCR. Ribavarin was maintained and interferon alpha-2b was stopped. Upper-gastrointestinal endoscopy showed a flat duodenal mucosa. Distal duodenal histology resulted in total villous atrophy. Positive antibodies to endomysium and the response to gluten-free diet enabled us to make a diagnosis of coeliac disease. The archival serum samples obtained before interferon and ribavarin treatment were positive for antibodies to endomysium. 10 days after she started a gluten-free diet, diarrhoea disappeared, the patient gained weight, and hydroelectroytic disorders were corrected, and we were able to renew interferon treatment. In September, 1997, we assessed a woman aged 31 years with coeliac disease for antiendomysium positivity, total villous atrophy on distal duodenal histology, and healing of intestinal architecture after 1 year of gluten withdrawal, underwent 1 year of treatment with interferon alfa-2b (3 MU three times weekly) for chronic active hepatitis C on liver biopsy. No effects from interferon were seen with the gluten-free diet. The patient was non-responder and from November, 1999, to October, 2000, she underwent a second treatment with interferon alpha-2b (6 MU three times weekly for 24 weeks, then 3 MU three times weekly for 24 weeks) plus ribavarin 1 g daily. Again, she had no adverse effects. We agree with Cammarota and colleagues that patients with chronic hepatitis C must be screened for endomysium before interferon treatment given the high prevalence of the disease in the general population (one per 200).3 Interferon treatment is possible in conjunction with a strict gluten-free diet. *Marc Bourlière, Valérie Oulés, Hervé Perrier, Cécile Mengotti Department of Hepato-Gastroenterology, Hôpital Saint Joseph, 13008, Marseille, France (e-mail: [email protected])
804
1
2
3
Cammarota G, Cuoco L, Cianci R, Pandolfi F, Gasbarrini G. Onset of coeliac disease during treatment with interferon for chronic hepatitis C. Lancet 2000; 356: 1494–95. Bardella MT, Marino R, Meroni PL. Celiac disease during interferon treatment. Ann Intern Med 1999; 131: 157–58. Maki M, Collin P. Coeliac disease. Lancet 1977; 349: 1755–59
Fluticasone and asthma Sir—We would like to comment on the statement made by Woodstock and colleagues (Nov 11, p 1682).1 They claim that the determination of volume of distribution in a study by Thorsson and colleagues2 is incorrect. Woodstock and colleagues’ reasoning is based on the low dose used by those investigators, which does not permit adequate detection. The statement is not, however, valid, since Thorsson and colleagues used tritiumlabelled compound, which increased assay sensitivity seven-fold compared with the assay used in the study by Martin Brutsche and colleagues3 of inhaled fluticasone propionate in patients with asthma and healthy volunteers, on which Woodstock and colleagues comment. The two assays allowed accurate measurement of fluticasone in plasma for 10–12 h. Surprisingly, Brutsche and colleagues did not take full advantage of their use of the high dose of fluticasone, which, according to our estimates, would allow measurement of the half-life of the drug from samples up to 48 h. In Thorsson and colleagues’ and Brutsche and colleagues’ studies sampling was stopped at 12 h, which is a shortcoming of each because of possible underestimation of half-life and inaccurate measurement of volume of distribution. To overcome this inadequate estimation, single dose inhalation data, with plasma concentrations for up to 48 h, were fitted simultaneously with the intravenous data to a model that gave a more reliable estimate of the half-life and the volume of distribution in the study by Thorsson and colleagues. The long half-life, the large volume of distribution, and the plasma accumulation of fluticasone seen with repeated dosing are indeed atypical when compared with other inhaled corticosteroids, and are most likely related to the high lipophilicity of the drug. Staffan Edsbäcker, Lars Thorsson Experimental Medicine, AstraZeneca R&D Lund, s-221 87 Lund, Sweden (e-mail: [email protected])
1
2
3
Woodcock A, Daley-Yates PT. Fluticasone propionate bioavailability in asthma. Lancet 2000; 356: 1682. Thorsson L, Dahlström K, Edsbäcker S, Kallén A, Paulson J, Wirén J-E. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1997; 43: 155–61. Brutsche MH, Brutsche IC, Munawar M, et al. Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study. Lancet 2000; 356: 556–61.
Discomfort with fineneedle aspiration cytology of the breast Sir—In their Nov 18 Commentary, Sutini Ngadiman1 and colleagues discuss keeping to a minimum discomfort during fine-needle aspiration (FNA) cytology of the breast. As they comment, I Daltrey and colleagues2 report use of blue-hub 23G needles without local anaesthesia as the choice for breast FNA. Bluehub needles give as good a cytological yield as a 21G needle.3 In our practice, we found that infiltration of local anaesthetic lateral to the incision site provided effective postoperative analgesia after surgical excision of breast lumps (unpublished data). We therefore did a prospective study to investigate whether a similar technique of anaesthetic infiltration lateral to the breast lump before FNA decreased pain scores. We studied 50 consecutive patients who underwent two diagnostic FNAs as part of investigation of benign breast lumps to assess degree of pain experienced and quality of prepared smears, with and without local anaesthesia. Our practice has a surgeon and cytopathologist in attendance at each breast clinic, and the cytopathologist (NA) does all aspirations. FNAs were done without local anaesthesia on the first visit. On the second visit, 5 mL 0·5% bupivocaine was injected lateral to the breast lump and FNA was done 20–30 min later. The patients were instructed to score the pain experienced at the first FNA as 10 on a horizontal linear visual analogue scale ranging from 0 to 10, and each patient scored the second procedure relative to that score. 43 (86%) of 50 patients had significantly improved pain scores: median pain score 3 (range 0–10). The quality of the FNA smears prepared was the same, with and without local anaesthetic. The beneficial action of local
THE LANCET • Vol 357 • March 10, 2001
For personal use only. Reproduce with permission from The Lancet Publishing Group.