We investigated lung cancer in 99 patients with idiopathic pulmonary fibrosis (IPF). Lung cancer was found in 31 (31.3%) of 99 patients with IPF. Most (87.9%) tumors, including squamous cell carcinoma, were observed in the peripheral region of the lung, whereas the distribution of histologic types of cancers was similar to that seen in ordinary lung cancer. Peripheral tumors were frequently seen in the lower lobe, where fibrotic shadow was prominent. However, the severity of fibrosis was not related with the prevalence or histologic type of lung cancer. Two-thirds of IPF patients having a smoking history of over 40 years developed lung cancer. When compared with nonsmoking IPF control subjects, the relative risk of smoking in IPF patients was 3.5, identical with that reported for smokers in the general population. We suggest that smoking in patients with IPF is an additive risk factor for the development of lung cancer. We also speculate that the high prevalence of peripheral squamous cell carcinoma might be associated with cigarette smoking. lung cancer ; smoking ; idiopathic pulmonary fibrosis
To determine possible contribution of nitric oxide (NO) to the stimulatory action of beta-adrenoceptor agonist on ciliary motility, we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelial cells by photoelectric method and NO release by specific amperometric sensors for this molecule in vitro. Salbutamol increased CBF, an effect that was potentiated by superoxide dismutase. Pretreatment of cells with NG-nitro-L-arginine methyl ester (L-NAME) attenuated the salbutamol-induced increase in CBF, causing a rightward displacement of the concentration-response curve by 2-2.5 log units, whereas NG-nitro-D-arginine methyl ester had no effect. The inhibitory effect of L-NAME was reversed by L-arginine but not by D-arginine. Immersion of the NO-selective electrode in the medium containing epithelial cells detected baseline current of 4.6-14.5 pA, which was abolished by L-NAME. Salbutamol dose-dependently increased the concentration of NO in the medium, the maximal increase being 56.2 +/- 5.3 nM (mean +/- SE; P < 0.001). These results suggest that NO is spontaneously released by airway epithelium and that the enhanced release of this molecule may play a role in the beta-adrenoceptor-mediated stimulation of ciliary motility.
Excessive production of sputum is one of the major symptoms in patients with chronic airway diseases. Because endogenous prostaglandins may play a role in the regulation of airway secretions, blockade of cyclooxygenase pathway with indomethacin could decrease respiratory tract fluid and mucus by inhibiting Cl secretion and glandular secretion and by enhancing Na absorption across airway mucosa. To test this hypothesis, we studied the effect of inhaled indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, and bronchiectasis in a double-blind, placebo-controlled fashion. Patients who inhaled 2 ml of indomethacin (1.2 micrograms/ml) three times a day for 14 days showed a decrease in the amount of sputum, from 189 +/- 19 to 95 +/- 21 g/day (p less than 0.001) and an increase in the solid component of sputum without alterations in parameters of systemic inflammatory responses. Although pulmonary function remained unchanged, perceived dyspnea was improved so that Borg's ratio scale was decreased from 7.1 +/- 0.5 to 4.5 +/- 0.4 (p less than 0.01). Adverse effects, including hypotension and bronchoconstriction, were not observed. The reduction of sputum was accompanied by a significant decrease in the concentrations of prostaglandin (PG)E2, PGF2 alpha, thromboxane B2, and 6-oxo-PGF1 alpha in the sputum. Thus, indomethacin inhalation may be of value in reducing bronchorrhea sputum, probably through the inhibition of PG-dependent airway secretions.
We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro. Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect. The rank order potency of macrolide was roxithromycin > erythromycin >> clarithromycin. The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin. Roxithromycin increased intracellular cAMP concentrations. These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.
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