Bronchial mucus properties in lung cancer: relationship with site of lesion.

OBJECTIVE: To compare the biophysical properties of mucus from the left and right mainstem bronchi in patients undergoing diagnostic bronchoscopy because of a unilateral radiological abnormality. It was hypothesized that abnormalities in the properties of mucus would be greater on the side with the lesion and that this would be most obvious in patients with unilateral lung cancer. PATIENTS AND METHODS: Bilateral paired samples of bronchial mucus were taken from 38 nonatopic patients (aged 59.8+/-12.6 years) including 16 nonsmokers, 14 current smokers and eight exsmokers (more than one year). Twenty of the 38 patients had a radiologically defined unilateral abnormality. Eight of these 20, including one nonsmoker, had lung cancer. The viscoelastic properties of the collected mucus were determined by magnetic microrheometry, and the analysis was carried out without knowledge of the histological diagnosis or source. RESULTS: The rheological properties of mucus strongly suggested which was the abnormal side. Within the group of 20 patients with a unilateral radiological abnormality, mucus from the side of the lesion had a lower value of the loss tangent, tan d100 (P=0.004), indicating greater mucus recoil. This is consistent with poor mucus cough clearability on the lesion side. All eight cancer patients fit this mucus rheological pattern with a lower value of tan d100 on the affected side (P=0.007). Four of the five other patients with a similar mucus abnormality were categorized as high cancer risk by other criteria, while six of seven patients with mucus that did not have this abnormality were considered to be lower risk. Based on the mucus analysis done at the time of the bronchoscopy, two of the 'noncancer' patients initially designated as high risk had cancer detected after several months of follow- up. Only two of the 18 patients without a defined unilateral lesion fit the mucus 'cancer pattern'. CONCLUSIONS: These findings are consistent with the hypothesis that either abnormalities in mucus properties may represent a risk factor for the development of lung cancer or that bronchial mucus abnormalities may be associated with products secreted by the tumours that, in turn, may suppress mucus clearance.

Amiloride inhalation therapy in cystic fibrosis. Influence on ion content, hydration, and rheology of sputum.

Amiloride inhalation as treatment for cystic fibrosis (CF) lung disease has been shown in independent studies to increase mucus clearance by ciliary and/or cough action and to retard the decline in lung function. It is hypothesized that amiloride therapy decreases the excess sodium and water absorption that is a characteristic of CF airway epithelium and that it leads to an improvement in the rheologic properties of mucus favoring airway mucus clearance. The aim of this study was to investigate whether amiloride treatment (5 x 10(-3) M amiloride in one-third normal saline four times a day) would change sputum electrolyte composition in patients with CF after 25 wk of therapy as compared with placebo (one-third normal saline), and whether appropriate changes in sputum water content and rheologic properties would accompany any changes in electrolyte composition. Sputum samples were obtained from six patients with CF undergoing amiloride therapy, using the dental cotton protection technique to avoid salivary contamination. The samples were stored at -80 degrees C until analyzed. For electrolyte analyses an aliquot of the sputum (minimum, 30 mg) was analyzed with ion-selective electrodes for sodium and potassium, and a chloride meter was used to measure chloride content. Chronic (25-wk) amiloride therapy increased significantly the sputum sodium (94.8 +/- 16.4 to 121.4 +/- 15.4 mmol/L, p = 0.001) and chloride (64.4 +/- 11.8 to 77.2 +/- 8.0 mmol/L, p = 0.10) content when compared with 25 wk of saline treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Rheology of mucus and transepithelial potential difference: small airways versus trachea.

The transfer of water across the airway epithelium is closely related to the transepithelial potential difference (PD). Thus, PD should be directly involved in the regulation of airway intraluminal water content and, by extension, mucus rheology. Experiments by Boucher and co-workers (J Appl Physiol, 1980; 48: 169; and 1981; 51: 706) indicated that the values of PD in the small airways of dogs were considerably lower than in the trachea or mainstem bronchus. This fact suggests that water is increasingly removed from the airway lumen in the cephalad direction, and provides a possible mechanism whereby airway flooding is avoided as the total airway cross-section diminishes mouthward. We investigated this possibility by collecting and analysing mucus from the small airways and trachea of anaesthetized dogs and comparing our findings with measurements of PD. Mucus was collected on a cytology brush placed against the wall of the airway. Tracheal samples were taken from the lower lateral or anterior trachea, while small airway samples were taken from a 6th or 7th generation bronchus, chosen at random from either side. Measurements of PD were made at comparable sites. The mucus was analysed for its viscoelastic properties using the magnetic microrheometer technique. PD in the 6th-7th generation bronchus was significantly less than in the lower trachea (4.1 +/- 1.3 vs 17.2 +/- 7.1 mV). The rigidity of mucus collected from the small airways (log mechanical impedance (G*) at 100 rad.s-1) was significantly less than in the trachea (2.81 +/- 0.22 vs 3.01 +/- 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory mucus from asymptomatic smokers is better hydrated and more easily cleared by mucociliary action.

We compared the physical and transport properties of tracheal mucus collected from 16 asymptomatic smokers and from 18 nonsmokers. The smokers produced a larger volume of mucus (wet weight 18.6 versus 11.2 mg; p = 0.04) with a lower solids content (11.5 versus 16.3%; p = 0.02) and a lower modulus of rigidity (log G* 2.37 versus 2.62; p = 0.04). Although the smokers mucus had a 40% faster mucociliary transport rate on the frog palate (p = 0.04), the cough clearability was nearly identical to the mucus from nonsmokers. The differences are similar to those observed in rats or dogs chronically exposed to cigarette smoke. These data suggest both a quantitative and a qualitative difference in the composition of mucus from asymptomatic smokers. The increased volume of a watery mucus with increased mucociliary clearability may help to protect the airways from the injurious effects of inhaled smoke.

Tracheal mucus rheology in patients undergoing diagnostic bronchoscopy. Interrelations with smoking and cancer.

We examined the differences in tracheal mucus rheology between nonsmokers and smokers, and between smokers with and without lung cancer. Mucus was collected from patients undergoing diagnostic bronchoscopy without atropine by holding a cytology brush in contact with the tracheal mucosa for 10 to 15 s. Samples were obtained from 43 patients 24 to 79 yr of age: nine nonsmokers, 18 current smokers, and 16 exsmokers (greater than 6 months); 12 patients (nine smokers, three exsmokers) had lung cancer. Pulmonary function testing showed that the nonsmoker patients had significant restrictive lung disease, and the patients with cancer had significant irreversible airway obstruction. The viscoelastic properties of the mucus samples were determined by magnetic microrheometry. Two parameters are reported: G* (modulus of rigidity) and tan delta (loss tangent), each measured at 1 and 100 rad/s. G* is an index of overall deformability (elastic and viscous), and tan delta is the ratio of viscous to elastic deformability. For nonsmoker patients, the viscoelastic parameters were virtually identical to those found previously for normal volunteers. For smokers without cancer, the mucus had a lower value of tan delta 1 rad/s and therefore was predicted to be more easily transportable by ciliary action; for exsmokers without cancer, ciliary transportability as calculated from viscoelasticity was even higher because of both low tan delta and low G*. Mucus from patients with cancer was not significantly different from that of nonsmokers; however, the mucus was predicted to be less easily clearable by ciliary action than was that from smokers and exsmokers without cancer, mainly because of a higher tan delta at 1 rad/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Collection and analysis of respiratory mucus from subjects without lung disease.

We collected the respiratory mucus coating the endotracheal tubes used during short surgical procedures in 27 patients with no clinical evidence of respiratory disease. Twelve were male and 15 were female, and they ranged from 1 to 64 yr of age (mean, 28.7 yr). The viscoelastic properties, frog palate transport rate, and percent solid composition were in the normal range reported for both canine and human mucus collected using the bronchoscopy brush technique. There were no significant differences noted between male and female patients, and there were no changes in mucus or transport properties seen with aging. Mucus was also collected separately from the inside of the tube exposed to constant gas flow (13 patients), and from the outside of the endotracheal tubes in 25 patients. Although there were no significant differences in viscoelastic properties between inside and outside mucus, there was a greater thread formation (filance, 45 versus 26 mm; p less than 0.005) and a higher percentage of solids in mucus from the inside of the endotracheal tube (15.9 versus 11.4%; p less than 0.05), which is compatible with reduced hydration. The duration of anesthesia ranged from 25 to 195 min (mean, 85 min). There was no effect of duration of anesthesia on any of the measured mucus properties. This technique for mucus collection allows us to study alterations in mucus properties in patients with and without pulmonary disease at the time of incidental surgery.(ABSTRACT TRUNCATED AT 250 WORDS)