Affiliations: Tokyo Women’s Medical University School of Medicine
Correspondence to: Jun Tamaoki, MD, FCCP, Tokyo Women’s Medical University School of Medicine, 8–1 Kawada-Cho, Shinjuku, Tokyo 162-8666, Japan; e-mail: firstname.lastname@example.org
In patients with bronchioloalveolar carcinoma, airway
obstruction by a copious amount of sputum provides a risk for
respiratory failure and even death.1Homma et al
(CHEST; May 1999)2 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.3 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.
The 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.
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