Inhaled Indomethacin in Bronchorrhea in Bronchioloalveolar Carcinoma
2000; Elsevier BV; Volume: 117; Issue: 4 Linguagem: Inglês
10.1378/chest.117.4.1213
ISSN1931-3543
AutoresJun Tamaoki, K. Kohri, Kazuo Isono, Atsushi Nagai,
Tópico(s)Lung Cancer Treatments and Mutations
ResumoTo the Editor:In patients with bronchioloalveolar carcinoma, airway obstruction by a copious amount of sputum provides a risk for respiratory failure and even death.1Hidaka N Nagao K Bronchioloalveolar carcinoma accompanied by severe bronchorrhea.Chest. 1996; : 281-282Abstract Full Text Full Text PDF Scopus (22) Google Scholar Homma et al (CHEST; May 1999)2Homma S Kawabata M Kishi K et al.Successful treatment of refractory bronchorrhea by inhaled indomethacin in two patients with bronchioloalveolar carcinoma.Chest. 1999; 115: 1465-1468Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar have shown that inhaled indomethacin reduces refractory bronchorrhea in bronchioloalveolar carcinoma, suggesting a role of cyclooxygenase in airway hypersecretion in this disease.We thus studied the effect of inhaled indomethacin on sputum production and the expression of cyclooxygenase-2 (COX-2) messenger RNA (mRNA) in seven patients with bronchioloalveolar carcinoma having bronchorrhea. A transbronchial lung biopsy was taken from the most affected area, and the gene expression was assessed by Northern blotting. The COX-2 primers were 5′-GTCTGATGATGTATGCCACAATCTG-3′ (sense) and 5′-GATGCCAGTGATAGAGGGTGTTAAA-3′ (antisense), giving rise to a 276-base pair polymerase chain reaction product.3Eberhart CE Coffey RJ Radhika A et al.Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas.Gastroenterology. 1994; 107: 1183-1188Abstract Full Text PDF PubMed Scopus (2340) Google Scholar Then, each patient received inhaled indomethacin, 75 mg/d, for 4 weeks, while the sputum expectorated was collected and weighed daily, and the values were reduced to weekly averages. A comparison between two groups, one showing positive for COX-2 mRNA expression and another negative, was made by analysis of variance and Scheffé's test.The expression of COX-2 mRNA was detected in four patients. During the baseline period, a mean sputum production was greater in the COX-2 messenger RNA-positive group (570 g/d) than in the COX-2 mRNA-negative group (165 g/d, p = 0.033; Fig 1). After the 4-week treatment, daily production of sputum decreased in the COX-2 mRNA-positive group by a mean ± SD of 49 ± 17% (p = 0.025), but it remained unchanged in the COX-2 mRNA-negative group. With respect to the change from baseline value, there was a significant difference between the two groups (p = 0.029). Therefore, upregulation of COX-2 in carcinoma cells and the resultant synthesis of cyclooxygenase products of arachidonic acid may be involved in the pathogenesis of bronchorrhea in bronchioloalveolar carcinoma, and blockade of COX-2 seems effective in the treatment of this condition. To the Editor:In patients with bronchioloalveolar carcinoma, airway obstruction by a copious amount of sputum provides a risk for respiratory failure and even death.1Hidaka N Nagao K Bronchioloalveolar carcinoma accompanied by severe bronchorrhea.Chest. 1996; : 281-282Abstract Full Text Full Text PDF Scopus (22) Google Scholar Homma et al (CHEST; May 1999)2Homma S Kawabata M Kishi K et al.Successful treatment of refractory bronchorrhea by inhaled indomethacin in two patients with bronchioloalveolar carcinoma.Chest. 1999; 115: 1465-1468Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar have shown that inhaled indomethacin reduces refractory bronchorrhea in bronchioloalveolar carcinoma, suggesting a role of cyclooxygenase in airway hypersecretion in this disease.We thus studied the effect of inhaled indomethacin on sputum production and the expression of cyclooxygenase-2 (COX-2) messenger RNA (mRNA) in seven patients with bronchioloalveolar carcinoma having bronchorrhea. A transbronchial lung biopsy was taken from the most affected area, and the gene expression was assessed by Northern blotting. The COX-2 primers were 5′-GTCTGATGATGTATGCCACAATCTG-3′ (sense) and 5′-GATGCCAGTGATAGAGGGTGTTAAA-3′ (antisense), giving rise to a 276-base pair polymerase chain reaction product.3Eberhart CE Coffey RJ Radhika A et al.Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas.Gastroenterology. 1994; 107: 1183-1188Abstract Full Text PDF PubMed Scopus (2340) Google Scholar Then, each patient received inhaled indomethacin, 75 mg/d, for 4 weeks, while the sputum expectorated was collected and weighed daily, and the values were reduced to weekly averages. A comparison between two groups, one showing positive for COX-2 mRNA expression and another negative, was made by analysis of variance and Scheffé's test.The expression of COX-2 mRNA was detected in four patients. During the baseline period, a mean sputum production was greater in the COX-2 messenger RNA-positive group (570 g/d) than in the COX-2 mRNA-negative group (165 g/d, p = 0.033; Fig 1). After the 4-week treatment, daily production of sputum decreased in the COX-2 mRNA-positive group by a mean ± SD of 49 ± 17% (p = 0.025), but it remained unchanged in the COX-2 mRNA-negative group. With respect to the change from baseline value, there was a significant difference between the two groups (p = 0.029). Therefore, upregulation of COX-2 in carcinoma cells and the resultant synthesis of cyclooxygenase products of arachidonic acid may be involved in the pathogenesis of bronchorrhea in bronchioloalveolar carcinoma, and blockade of COX-2 seems effective in the treatment of this condition. In patients with bronchioloalveolar carcinoma, airway obstruction by a copious amount of sputum provides a risk for respiratory failure and even death.1Hidaka N Nagao K Bronchioloalveolar carcinoma accompanied by severe bronchorrhea.Chest. 1996; : 281-282Abstract Full Text Full Text PDF Scopus (22) Google Scholar Homma et al (CHEST; May 1999)2Homma S Kawabata M Kishi K et al.Successful treatment of refractory bronchorrhea by inhaled indomethacin in two patients with bronchioloalveolar carcinoma.Chest. 1999; 115: 1465-1468Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar have shown that inhaled indomethacin reduces refractory bronchorrhea in bronchioloalveolar carcinoma, suggesting a role of cyclooxygenase in airway hypersecretion in this disease. We thus studied the effect of inhaled indomethacin on sputum production and the expression of cyclooxygenase-2 (COX-2) messenger RNA (mRNA) in seven patients with bronchioloalveolar carcinoma having bronchorrhea. A transbronchial lung biopsy was taken from the most affected area, and the gene expression was assessed by Northern blotting. The COX-2 primers were 5′-GTCTGATGATGTATGCCACAATCTG-3′ (sense) and 5′-GATGCCAGTGATAGAGGGTGTTAAA-3′ (antisense), giving rise to a 276-base pair polymerase chain reaction product.3Eberhart CE Coffey RJ Radhika A et al.Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas.Gastroenterology. 1994; 107: 1183-1188Abstract Full Text PDF PubMed Scopus (2340) Google Scholar Then, each patient received inhaled indomethacin, 75 mg/d, for 4 weeks, while the sputum expectorated was collected and weighed daily, and the values were reduced to weekly averages. A comparison between two groups, one showing positive for COX-2 mRNA expression and another negative, was made by analysis of variance and Scheffé's test. The expression of COX-2 mRNA was detected in four patients. During the baseline period, a mean sputum production was greater in the COX-2 messenger RNA-positive group (570 g/d) than in the COX-2 mRNA-negative group (165 g/d, p = 0.033; Fig 1). After the 4-week treatment, daily production of sputum decreased in the COX-2 mRNA-positive group by a mean ± SD of 49 ± 17% (p = 0.025), but it remained unchanged in the COX-2 mRNA-negative group. With respect to the change from baseline value, there was a significant difference between the two groups (p = 0.029). Therefore, upregulation of COX-2 in carcinoma cells and the resultant synthesis of cyclooxygenase products of arachidonic acid may be involved in the pathogenesis of bronchorrhea in bronchioloalveolar carcinoma, and blockade of COX-2 seems effective in the treatment of this condition. Inhaled Indomethacin in Bronchorrhea in Bronchioloalveolar Carcinoma: Role of CyclooxygenaseCHESTVol. 117Issue 4PreviewThe comments by Tamaoki and coworkers on our article (CHEST; May 1999)1 show the importance of the expression of COX-2 messenger RNA in carcinoma cells. The results are very useful in establishing treatment with inhaled indomethacin for bronchorrhea in patients with bronchioloalveolar carcinoma. Tamaoki and colleagues demonstrated the theoretical reason why there are two groups of bronchioloalveolar carcinoma patients: one group that is responsive to inhaled indomethacin and the other group that is not responsive. Full-Text PDF
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