The Role of Cough in Lung Mucus Clearance

Mucus secretion, cellular debris, and any insoluble deposited particles can be cleared from the conducting airways of the human lungs by two main clearance mechanisms: mucociliary and cough clearance. These clearance mechanisms help to keep the lungs clear and free from infection and pollutants.Cough is an important defense mechanism of the lungs. It is a reserve mechanism for mucus clearance (1). Cough rarely occurs in healthy subjects ex­cept in emergency situations, following the inhalation of a foreign body or bron­chial irritants. It can come dramatically into action in airway diseases where mucociliary transport is often compromised (2) and the increased amount of se­cretions cannot be adequately removed by mucociliary clearance. RADIOAEROSOL TECHNIQUE FOR MEASURING MUCUS TRANSPORT

The radioaerosol technique is now widely used for measuring lung mucus trans­port in humans (3). This technique involves the inhalation of an insoluble aerosol firmly labeled with a gamma-emitting radioisotope. The radiation from the sub399

ject’s chest can be monitored by external scintillation counters or a gamma cam­era, and therefore the initial radioaerosol deposition in the lungs can be deter­mined. Sequential counting of the lung radioactivity shows a progressive fall due to two factors: biological clearance of the radioaerosol and physical decay of the radionuclide. Correction for the physical decay can readily be made knowing the physical half-life of the radionuclide and a lung clearance curve can be obtained for the radioactivity remaining in the lungs (as a percentage of the initial count) against time.It is conventionally accepted that the lung retention of radioaerosols 24 hours postinhalation indicates the proportion of the inhaled aerosols deposited in the alveolar region of the lungs (4). Even though this assumption may not be totally valid, the estimate of alveolar deposition so obtained when subtracted from the lung clearance curve gives a tracheobronchial clearance curve. This curve represents the amount of radioaerosol that was cleared from the conducting airways.Aerosol particles can be produced by a jet or ultrasonic nebulizer (5) or by a spinning disc generator (6). The last apparatus is capable of producing mono-disperse aerosols of any size in the range of 1-10 pm. A variety of aerosols are being used for measuring lung mucus clearance including polystyrene, iron oxide, Teflon, Lucite, and resin (7). These insoluble aerosols are labeled with several types of gamma-emitting radionuclides (5). The most widely used radioisotope for labeling aerosol particles is technetium-99m (99mTc).The radioaerosols should be administered to human subjects under con­trolled conditions to minimize variability in their initial topographical distribution and hence in the measurement of mucus clearance. The system for the generation of radioaerosols and their delivery needs to be reliable and simple so as to get the required deposition within the lungs. Deposition of inhaled particles in the lungs in inevitably affected by the physical properties and the mode of inhalation of the aerosol as well as the patency of the airways (8). WHOLE LUNG CLEARANCE

Many studies evaluating the efficacy of cough on the transport of inhaled depos­ited radioaerosol particles from the human lungs have been reported. Toigo and associates (9) suggested that cough increased the clearance of labeled carbon particles (40-70 pm in diameter) in eight healthy subjects and eight patients with chronic lung disease. They observed that after each cough the amount of radia­tion, measured over the carina, dropped sharply. However, Yeates and associates (10) studying 42 healthy nonsmoking adults reported that coughing did not greatly affect the movement of a local concentration (bolus) of microspheres in the trachea, whereas coughing was the major clearance mechanism from the tra­chea in patients with cystic fibrosis (11). These results were confirmed by Pu-

chelle and associates (12) in patients with chronic bronchitis. The mean percent­age of bronchial radioactivity cleared after one hour from inhalation by mucociliary clearance in 10 healthy subjects was 30%, which was about twice that eliminated by 27 chronic bronchitics (14%). At the end of the one-hour period, the healthy subjects and patients were asked to cough and the percentage of retained bronchial radioactivity was measured again. The chronic bronchitics eliminated a further 20% compared to the healthy subjects, who cleared only 2.5%. This study demonstrated that in the chronic bronchitics a high percentage of deposited particles was cleared by coughing, while in the healthy subjects this was not so. The effect of cough was also studied in eight patients with respiratory tract disease and six healthy subjects by Camner and associates (13). The healthy subjects did not produce any sputum and did not clear any test particles on in­structed vigorous coughing, whereas the patients who produced sputum (6 of 8) were able to clear test particles from their lungs by coughing.It thus appears that the presence of an increased amount of mucus is an essential prerequisite for cough to be effective as a clearance mechanism. We have reported that tracheobronchial clearance of deposited radioaerosol was faster in chronic bronchitic patients who produced a high volume of sputum and coughed frequently (14). We also suggested that cough may be a very important clearance mechanism in asthma (15). During the first 2 hours of the study, the asthmatic patients who coughed frequently cleared more than twice as much ra­dioaerosol as the asthmatic patients who coughed less despite a slightly higher initial radioaerosol penetration.Voluntary coughing in 12 patients with immotile-cilia syndrome was also found to be an important clearance mechanism (16); on average, 30% of the deposited particles were removed after coughing. Directed coughing was evalu­ated in 10 patients with obstruction and copious sputum by Sutton and associates (17). Each patient underwent a 30-minute treatment period in which the patients were asked to cough and another 30 minutes as a control period after inhaling radioaerosol particles. The percentage of radioactivity remaining in the lungs after the treatment period was less than the control period, during which the reduction in radioactivity was due to mucociliary clearance and spontaneous coughing.The effect of a controlled coughing maneuver (10 coughs every 10 minutes for 1 hour) compared to a control period in 12 nonsmoking healthy subjects was investigated by Bennett and associates (18). The controlled cough consisted of forceful exhalation against a closed solenoid valve, which automatically opened after a threshold airway pressure was reached. The amount of radiolabeled parti­cles retained after the coughing maneuver were significantly less than that re­tained during the control period. The same results were observed with rapid inha­lations (90 inhalations per hour) rather than exhalations (coughs) when compared to a control period in eight healthy subjects. Therefore, they postulated that the

observed enhancement of mucus clearance by controlled coughing might be due to a stimulation of the mucociliary mechanism. However, using the same proto­col, 10 young asymptomatic smokers were unable to enhance their rate of mucus clearance by coughing or rapid inhalations suggesting a change in the mucociliary transport from normal (19). REGIONAL LUNG CLEARANCE

Estimation of regional mucus clearance has been carried out by relatively few investigators. There has been general agreement that cough significantly enhances the clearance of mucus from the lungs as a whole and from the central region and that it almost fully compensates for a defective mucociliary clearance in patients with hypersecretion. However, attempts to study lung mucus clearance from the peripheral region have yielded contradictory results.Oldenburg and colleagues (20), studying eight patients with obstructive chronic bronchitis (mean % predicted FEVi was 53) and producing sputum vol­umes ranging from 10 to 120 mL/day, found that coughing produced a very significant effect on whole lung and peripheral lung mucus clearance. Using simi­lar technique, Bateman and associates (21) studied six patients (three chronic bronchitics and three bronchiectatics) who were more severely obstructed (mean % predicted FEV, was 37) and were producing larger sputum volumes (50-300 mL/day). Mucus clearance during cough was significantly increased from the whole lung and central and intermediate regions. However, no significant effect on clearance from the peripheral region was noted, and that differs from the study of Oldenburg and colleagues (20). It is possible in the Oldenburg study that the significant mucus clearance reported from the peripheral region reflected clear­ance from larger conducting airways since the proximal boundary of the periph­eral region corresponded approximately to 2-4 mm airways (i.e., in the peripheral region there must have existed large airways). Furthermore, in the study of Old­enburg the initial radioaerosol deposition was more central than in the Bateman study (21).Six patients with cystic fibrosis were studied by Rossman and associates (22). The mean % predicted FEV, was 38 and the mean sputum volume was 67 mL/day. The effect of cough on mucus clearance was similar to that reported by Oldenburg and associates study (20), where after coughing the mucus trans­ported from the peripheral region of the lungs was increased as well as from the central region.We have shown that cough is effective in clearing lung secretions from central and intermediate regions in a group of 19 patients with airways obstruction with mean % predicted FEV, of 52 and sputum wet weight of 37 mL/day (23). This is in agreement with the Bateman and colleagues study (21) but in contrast with those reported by Oldenburg and associates (20) and Rossman and col­

leagues (22). The apparent discrepancy may have arisen because of differences in the selection of regions of interest between those studies and because more of the radiotracer (20% approximately) was deposited in the outer region in the studies of Bateman and ours than in the other two studies (12.5% approximately). However, in another group of 14 patients with airways obstruction (mean % predicted FEV, was 54 and sputum production was 9 mL/day) we were able to demonstrate that cough resulted in movement of secretions proximally from all regions of the lungs (24). These findings were supported by the study of Bennett and associates (25), which also demonstrated that voluntary cough was effective in clearing lung secretions from the central as well as the peripheral regions of the lungs. The reason that cough in our study (23) did not achieve significant level in clearing lung secretions from the peripheral airways could be attributed to the amount of daily sputum produced by the patients.Recently we evaluated the effect of different airway diseases on lung mucus transport during instructed coughing (26). Cough was able to significantly en­hance the movement of mucus from the central and peripheral regions of the lungs in eight patients with chronic bronchitis (mean ± SEM % predicted FEV, of 41 ± 3). However, in two groups of eight patients with asthma and eight patients with bronchiectasis (Mean ± SEM % predicted FEV, of 65 ± 6 and 57 ±10, respectively), cough was only able to significantly enhance clearance from the central region of the lungs (Fig. 1). These results were control corrected where

patients did not cough, and thus mucus clearance was primarily achieved by mucociliary transport mechanism. The difference in cough action in chronic bron­chitic, asthmatic, and bronchiectatic patients could be due to differences in physi-ochemical properties of mucus in each group. CONCLUSION

Cough in patients with airways obstruction results in an improvement of whole lung clearance and movement of secretions proximally from all regions of the lungs. As such coughing (productive or unproductive) must be partly compensat­ing for the well-documented compromised mucociliary transport in such patients. It therefore follows that allowance should be made for coughing when interpret­ing lung mucociliary clearance curves. REFERENCES

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