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Abnormal nasal mucociliary clearance in patients with rhinitis and its relationship to concomitant chest disease
Br. J. Dis.
Chest
(1985) 79, 77
ABNORMAL NASAL MUCOCILIARY CLEARANCE IN PATIENTS WITH RHINITIS AND ITS RELATIONSHIP TO CONCOMITANT CHEST DISEASE P. J. STANLEY, Host
Defence Unit, Department,
R. WILSON, M. A. GREENSTONE, AND P. J. COLE
I. S. MACKAY*
Department of Medicine, Cardiothoracic Institute Brompton Hospital, Fulham Road, London, SW3
and 6HP
*ENT
Summary
Nasal mucociliary clearance was measured using a saccharin technique in 172 patients with perennial rhinitis (76 also had asthma) and in 12 1 patients with chronic infected rhinosinusitis (40 had asthma, 35 had bronchiectasis). All patient groups had significantly longer mean nasal mucociliary clearance times than that of a group of healthy subjects. Grossly prolonged clearance (>60 minutes) occurred in significantly more patients with the clinical syndrome of chronic infected rhinosinusitis and bronchiectasis than in the syndromes of chronic infected rhinosinusitis with or without asthma, and perennial rhinitis with or without asthma. The abnormal clearance was shown not to be due to an intrinsic ciliary defect by in vitro examination of nasal cilia but probably to be due to a combination of mucus and ciliary factors in vivo. Introduction
Mucociliary clearance is an important defence mechanism of the upper and lower respiratory tracts. Delayed clearance, whether primary or secondary, may lead to retention of particulate matter, e.g. microorganisms or allergens which may then cause or exacerbate existing disease. Mucociliary clearance (MCC) in the tracheobronchial tree is impaired in chronic pulmonary disorders such as asthma (Pavia et al. 1980), bronchiectasis (LourenCo et al. 1972) and chronic obstructive lung disease (Camner et al. 1973b). I n chronic nasal disease, however, although some workers have reported slower nasal MCC in chronic sinusitis (Majima et al. 1983) others have shown acceleration of clearance in this disease and in allergic rhinitis (Hady et al. 1983). Nasal MCC can be measured using a simple, inexpensive and non-invasive, saccharin method first described by Andersen et al. (1974), which can be used to screen large numbers of patients to detect abnormal clearance (Stanley et al. 1984b). We present a study using this technique to investigate nasal mucociliary clearance in patients who have perennial rhinitis or chronic infected rhinosinusitis with or without concomitant asthma or bronchiectasis.
78
P. J. Stanley et al. Methods
Saccharin test The time from placement of a 1 mm diameter particle of saccharin on the inferior nasal turbinate, 1 cm from its anterior end, to the subject’s first experience of a sweet taste was recorded in minutes. The subject was positioned with head slightly forward and requested not to sniff, sneeze, cough, eat or drink during the test. Subjects who failed to taste within 60 minutes were considered to have grossly prolonged nasal MCC after their ability to taste saccharin placed on the tongue had been verified. The nasal cilia, obtained by a brushing technique, of patients with grossly prolonged nasal MCC were examined for beat frequency using a photometric technique (Rutland & Cole 1980) and per cent motility (Greenstone et al. 1984). Patients The patients studied were attending Brompton Hospital Nose Clinic for the first time with the following clinical syn&omes: perennial allergic rhinitis with no chest disease (31 males, 19 females; mean age 34.2116.6 (SD) years); perennial allergic rhinitis with asthma (26 M, 27 F; age 34.12 15.6 years); perennial non-allergic rhinitis with no chest disease (21 M, 26 F; age 37.8k16.4 years); perennial non-allergic rhinitis with asthma (7 M, 16 F; age 52.9-tl5.7 years); chronic infected rhinosinusitis with no chest disease (21 M, 25 F; age 38.3k17.0 years); chronic infected rhinosinusitis with asthma (17 M, 23 F, age 41 .l+ 16.7 years); chronic infected rhinosinusitis with clinical or radiographic evidence of bronchiectasis (13 M, 22 F; age 37.7+ 14.1 years). For the purposes of this study, perennial allergic rhinitis was defined as at least 12 months’ history of watery rhinorrhoea, nasal obstruction and/or sneezing with exacerbation of symptoms on exposure to an allergen or more than two positive skin prick tests to common perennial inhalant allergens. Perennial non-allergic rhinitis was diagnosed by a history of at least 12 months of watery rhinorrhoea, nasal obstruction and/or sneezing with no history of exacerbation by allergens and negative skin prick tests to common allergens. Chronic infected rhinosinusitis was defined as greater than 6 months’ history of mucopurulent rhinorrhoea or postnasal discharge with abnormal sinus radiographs. All of the 35 patients with bronchiectasis had a history of chronic purulent sputum production and there were localized crackles in the chest. In four the chest radiograph was normal and in five it was abnormal with changes suggestive of bronchiectasis; in the remaining 26 patients bronchograms were performed to demonstrate the bronchiectasis. Nasal MCC has been found to be delayed in chronic cigarette smokers (Stanley et al. 1984a), therefore, patients who were current or recent (<3 months) smokers were excluded from the study. Also excluded were patients who had nasal obstruction with expiratory nasal resistance of greater than 12 cmHsO/litre/sec, measured by active anterior rhinomanometry (Mackay 1979), and those who were diagnosed as having primary ciliary dyskinesia after examination of their nasal cilia, Thirty-five healthy non-smoking subjects (15 M, 20 F; age 32.22 12.3 years) with no chronic respiratory tract disease or recent acute respiratory infection were also studied.
Results The healthy subjects had a mean nasal MCC time of 11.7k3.8 (SD) minutes and no subject had a clearance of >60 minutes. The numbers of patients with nasal MCC <60 minutes and with grossly prolonged clearance (>60 minutes) are shown in Table I. The proportion of patients with perennial rhinitis, whether allergic or non-allergic, with or without asthma, who had grossly prolonged nasal MCC was not significantly different from the healthy controls. However, the three groups of patients with chronic infected rhinosinusitis (CIR) all had a significantly greater proportion of patients with nasal MCC >60 minutes than controls. In the group with CIR and bronchiectasis more patients had nasal MCC >60 minutes than had nasal MCC <60 minutes, and this group was also
Abnormal Nasal Mucociliary
79
Clearance in Patients with Rhinitis
significantly different (P
1.
The number of patients and >60 minutes
with
nasal mucociliary
NMCC <60 min
NMCC XT0
clearance
(NMCC)
times <60 minutes
Probability of difference from healthy subjects
min
(A-squared)
AR & normal chest AR & asthma NAR & normal chest NAR & asthma CIR & normal chest CIR & asthma CIR & CPSP
48 49 45 20 34 33 15
2 4 2 3 12 7 20
AR, allergic rhinitis; NAR, non-allergic CPSP, chronic purulent sputum production. Table
II. The mean nasal mucociliary minutes
clearance
NS Xi KS NS P
rhinitis;
CIR,
(NMCC)
times for subjects with clearance
Mean NMCC (min)
chronic
isD
Healthy subjects AR & normal chest AR & asthma NAR & normal chest NAR & asthma CIR & normal chest CIR & asthma CIR & CPSP
n=35 n=48 n=49 n=45 n=20 n=34 n=33
n=15
11.7k3.8 18.2k8.3 16.7kti.4 19.1k9.1 20.2k8.0 27.0-+_ 13.0 22.8k9.6 26.lrt_10.4
AR, allergic rhinitis; NAR, non-allergic chronic purulent sputum production.
rhinitis;
infected
rhinosinusitis;
Probabilip of difference healthy subjects (Mann-Whitney U test)
of <60
from
P
CIR,
chronic
infected
rhinosinusitis;
CPSP,
three groups with infected rhinitis. However, the mean nasal MCC time for patients with CIR was significantly longer (PcO.01; Mann-Whitney U test) than that of the patient groups with perennial rhinitis, except for the group with non-allergic rhinitis and asthma. Discussion Patients with perennial allergic, or non-allergic, rhinitis and to a greater extent those with chronic infected rhinosinusitis had prolonged nasal mucociliary
80
P. J. Stan@ et al.
clearance. Impairment of nasal MCC in patients with concomitant asthma was not significantly different from patients with no chest disease. However, nasal MCC was significantly more delayed in patients with chronic infected rhinosinusitis and bronchiectasis, 57% having nasal MCC >60 minutes, compared to other patients with infected or perennial rhinitis or normal subjects. All patients with infected rhinitis had similar upper respiratory clinical symptoms and signs, therefore the greater abnormalities of clearance seen in patients with concomitant bronchiectasis cannot be simply explained by differences in disease severity. Defective mucociliary transport can be considered to be due to abnormalities in its ciliary component, its mucus component or a combination of both components. None of the patients with grossly prolonged clearance had primary ciliary dyskinesia (any such patient having been excluded from the study) and previous work with a similar group of patients has shown that in vitro nasal ciliary beat frequency (CBF) and ciliary ultrastructure are within normal limits in the majority of patients with rhinitis and abnormal nasal MCC (Greenstone et al. 1983). However, in this study and in a study by Rutland and Cole (1981) CBF was statistically significantly slower, by approximately lo%, in patients with bronchiectasis although such a reduction in CBF may be of little biological significance. Nine of the ten patients in the latter study had nasal MCC (measured using the same saccharin method) of less than 60 minutes, therefore, this observed reduction in CBF is unlikely to be a major factor in producing the more severe abnormalities of clearance found in patients with bronchiectasis. Despite normal ciliary function in vitro, factors in mucus or serum could cause slowing of CBF or incoordination of cilia in vivo, or there may be loss of ciliated epithelium producing delayed MCC. Camner et al. (1973a) demonstrated a temporary defect in tracheobronchial MCC after influenza A virus infection which causes extensive destruction of ciliated epithelium (Hers et al. 1958). Reimer et al. (1978) examined the maxillary sinus mucosa of patients with chronic purulent sinusitis by scanning electron microscopy and found large areas of unciliated epithelium, although the remaining cilia exhibited a normal mucociliary wave frequency measured by an in vivo technique. Quantitative or qualitative differences in the bacterial flora between patients who have infected rhinitis with and without’ chronic lower respiratory tract sepsis might influence the degree of impairment of MCC and this aspect is at present under investigation. For eflicient mucociliary transport, mucus of optimal viscoelastic properties is necessary which, according to Dulfano and Adler (1975), is mucus of low viscosity and high elastic recoil. Infected mucus is more viscous than normal mainly due to increased DNA fibre content (Burgi 1973) and this may be a factor causing poor clearance in infected patients even if the cilia are beating normally. Majima et al. (1983), reported delayed nasal MCC in patients with chronic sinusitis and found that mucus from these patients was transported at a slower rate than normal mucus by the ciliated epithelium of an isolated bullfrog palate. However, there was no significant difference between the transport rate of mucus from patients with severely prolonged nasal MCC and that of mucus from patients
Abnormal Nasal Mucociliary
Clearance in Patients with Rhinitis
81
with only slightly delayed clearance. Mucus of low viscosity and low elasticity will also produce inefficient mucociliary transport. This may occur in patients with allergic, or non-allergic, non-infected rhinitis who characteristically have watery rhinorrhoea. Another factor of potential importance is uncoupling of the action of the cilia on overlying mucus by changes in the depth of the periciliary fluid layer (Proctor 1977). However, little is known about the factors controlling this fluid layer. The abnormal mucociliary clearance found in our patients is unlikely, therefore, to have a simple explanation, but is probably a combination of a change in mucus viscoelastic properties, alteration in the periciliary fluid layer, reduction in the number of cilia and possibly decreased motility of the cilia in vivo. Acknowledgements P.S. was supported by Berk Pharmaceuticals Ltd and R.W. by Janssen Pharmaceuticals Ltd. This work was supported by The Wellcome Trust and the National Fund for Research into Crippling Diseases. References Andersen, I., Camner, P., Jensen, P. L., Philipson, K. & Proctor, D. F. (1974) Nasal clearance in monozygotic twins. Am. Rev. resp. Dis. 110, 301-305. Burgi, H. (1973) Fibre systems in sputum. Bull. Physiopath. resp. 9, 191-196. Camner, P., Jarstrand, C. & Philipson, K. (1973a) Tracheobronchial clearance in patients with influenza. Am. Rev. resp. Dis. 108, 131-135. Camner, P., Mossberg, B. & Philipson, K. (1973b) Tracheobronchial clearance and chronic obstructive lung disease. Stand. J. resp. Dis. 54, 272-281. Dulfano, M. J. & Adler, K. B. (1975) Physical properties of sputum. VII. Rheologic properties and mucociliary transport. Am. Rev. resp. Dis. 112, 341-347. Greenstone, M. A., Stanley, P. J., Cole, P. J. & Mackay, I. S. (1984) Upper respiratory manifestations of primary ciliary dyskinesia. J. Laryngol. Otol. (in press). Greenstone, M. A., Stanley, P. J., MacWilliam, L., Dewar, A., Cox, T., Mackay, I. S. & Cole, P. J. (1983) Mucociliary function and ciliary ultrastructure in patients presenting with rhinitis to Brompton Hospital Nose Clinic. Eur. J. resp. Dis. 64, suppl. 128 (Part 2), 457-459. Hady, M. R. A., Shehata, 0. & Hassan, R. (1983) Nasal mucociliary function in different diseases of the nose. J. Laryngol. Otol. 97, 497-502. Hers, J. F. P., Masurel, N. & Mulder, J. (1958) Bacteriology and histopathology of the respiratory tract and lungs in fatal Asian influenza. Lancet 2, 1141-l 143. Lourenco, R. V., Loddenkemper, R. & Carton, R. W. (1972) Patterns of distribution and clearance of aerosols in patients with bronchiectasis. Am. Rev. resp. Dis. 106, 85&866. Mackay, I. S. (1979) Measurement of nasal airflow and resistance. J. R. Sot. Med. 72, 852-855. Majima, Y., Sakakura, Y., Matsubara, T., Murai, S. & Miyoshi, Y. (1983) Mucociliary clearance in chronic sinusitis; related nasal clearance and in vitro bullfrog palate clearance. Biorheology 20, 25 l-262. Pavia, D., Bateman, J. R. M. & Clarke, S. W. (1980) D ep osi‘t’ion and clearance of inhaled particles. Bull.
Proctor,
eur. Physiopath.
resp.
16, 335-366.
D. F. (1977) The upper airways. 1. Nasal physiology and defense of the lung. Am. Rev. resp. Dis. 115, 97-129. Reimer, A., von Mecklenburg, C. & Toremalm, N. G. (1978) The mucociliary activity of the upper respiratory tract. III. A functional and morphological study on human and animal material with special reference to maxillary sinus disease. Acta Otolaryngol. (Stockh.) suppl. 355, l-20.
P. J. Stanley et al. Rutland, J. & Cole, P. J. (1980) Non-invasive sampling of nasal cilia for measurement of beat frequency and study of ultrastructure. Lancet 2, 564-565. Rutland, J. & Cole, P. J. (1981) Nasal mucociliary clearance and ciliary beat frequency in cystic fibrosis compared with sinusitis and bronchiectasis. Thorax 36, 654-658. Stanley, P. J., MacWilliam, L., Greenstone, M. A., Daly, C. & Cole, P. J. (1984a) Prolonged nasal mucociliary clearance in smokers. Thorax 39, 239. Stanley, P. J., MacWilliam, L., Greenstone, M. A., Mackay, I. S. & Cole, P. J. (198413) Efficacy of a saccharin test for screening to detect abnormal mucociliary clearance. Br. J. Dis. Chest 78, 62-65.
Chest
(1985) 79, 77
ABNORMAL NASAL MUCOCILIARY CLEARANCE IN PATIENTS WITH RHINITIS AND ITS RELATIONSHIP TO CONCOMITANT CHEST DISEASE P. J. STANLEY, Host
Defence Unit, Department,
R. WILSON, M. A. GREENSTONE, AND P. J. COLE
I. S. MACKAY*
Department of Medicine, Cardiothoracic Institute Brompton Hospital, Fulham Road, London, SW3
and 6HP
*ENT
Summary
Nasal mucociliary clearance was measured using a saccharin technique in 172 patients with perennial rhinitis (76 also had asthma) and in 12 1 patients with chronic infected rhinosinusitis (40 had asthma, 35 had bronchiectasis). All patient groups had significantly longer mean nasal mucociliary clearance times than that of a group of healthy subjects. Grossly prolonged clearance (>60 minutes) occurred in significantly more patients with the clinical syndrome of chronic infected rhinosinusitis and bronchiectasis than in the syndromes of chronic infected rhinosinusitis with or without asthma, and perennial rhinitis with or without asthma. The abnormal clearance was shown not to be due to an intrinsic ciliary defect by in vitro examination of nasal cilia but probably to be due to a combination of mucus and ciliary factors in vivo. Introduction
Mucociliary clearance is an important defence mechanism of the upper and lower respiratory tracts. Delayed clearance, whether primary or secondary, may lead to retention of particulate matter, e.g. microorganisms or allergens which may then cause or exacerbate existing disease. Mucociliary clearance (MCC) in the tracheobronchial tree is impaired in chronic pulmonary disorders such as asthma (Pavia et al. 1980), bronchiectasis (LourenCo et al. 1972) and chronic obstructive lung disease (Camner et al. 1973b). I n chronic nasal disease, however, although some workers have reported slower nasal MCC in chronic sinusitis (Majima et al. 1983) others have shown acceleration of clearance in this disease and in allergic rhinitis (Hady et al. 1983). Nasal MCC can be measured using a simple, inexpensive and non-invasive, saccharin method first described by Andersen et al. (1974), which can be used to screen large numbers of patients to detect abnormal clearance (Stanley et al. 1984b). We present a study using this technique to investigate nasal mucociliary clearance in patients who have perennial rhinitis or chronic infected rhinosinusitis with or without concomitant asthma or bronchiectasis.
78
P. J. Stanley et al. Methods
Saccharin test The time from placement of a 1 mm diameter particle of saccharin on the inferior nasal turbinate, 1 cm from its anterior end, to the subject’s first experience of a sweet taste was recorded in minutes. The subject was positioned with head slightly forward and requested not to sniff, sneeze, cough, eat or drink during the test. Subjects who failed to taste within 60 minutes were considered to have grossly prolonged nasal MCC after their ability to taste saccharin placed on the tongue had been verified. The nasal cilia, obtained by a brushing technique, of patients with grossly prolonged nasal MCC were examined for beat frequency using a photometric technique (Rutland & Cole 1980) and per cent motility (Greenstone et al. 1984). Patients The patients studied were attending Brompton Hospital Nose Clinic for the first time with the following clinical syn&omes: perennial allergic rhinitis with no chest disease (31 males, 19 females; mean age 34.2116.6 (SD) years); perennial allergic rhinitis with asthma (26 M, 27 F; age 34.12 15.6 years); perennial non-allergic rhinitis with no chest disease (21 M, 26 F; age 37.8k16.4 years); perennial non-allergic rhinitis with asthma (7 M, 16 F; age 52.9-tl5.7 years); chronic infected rhinosinusitis with no chest disease (21 M, 25 F; age 38.3k17.0 years); chronic infected rhinosinusitis with asthma (17 M, 23 F, age 41 .l+ 16.7 years); chronic infected rhinosinusitis with clinical or radiographic evidence of bronchiectasis (13 M, 22 F; age 37.7+ 14.1 years). For the purposes of this study, perennial allergic rhinitis was defined as at least 12 months’ history of watery rhinorrhoea, nasal obstruction and/or sneezing with exacerbation of symptoms on exposure to an allergen or more than two positive skin prick tests to common perennial inhalant allergens. Perennial non-allergic rhinitis was diagnosed by a history of at least 12 months of watery rhinorrhoea, nasal obstruction and/or sneezing with no history of exacerbation by allergens and negative skin prick tests to common allergens. Chronic infected rhinosinusitis was defined as greater than 6 months’ history of mucopurulent rhinorrhoea or postnasal discharge with abnormal sinus radiographs. All of the 35 patients with bronchiectasis had a history of chronic purulent sputum production and there were localized crackles in the chest. In four the chest radiograph was normal and in five it was abnormal with changes suggestive of bronchiectasis; in the remaining 26 patients bronchograms were performed to demonstrate the bronchiectasis. Nasal MCC has been found to be delayed in chronic cigarette smokers (Stanley et al. 1984a), therefore, patients who were current or recent (<3 months) smokers were excluded from the study. Also excluded were patients who had nasal obstruction with expiratory nasal resistance of greater than 12 cmHsO/litre/sec, measured by active anterior rhinomanometry (Mackay 1979), and those who were diagnosed as having primary ciliary dyskinesia after examination of their nasal cilia, Thirty-five healthy non-smoking subjects (15 M, 20 F; age 32.22 12.3 years) with no chronic respiratory tract disease or recent acute respiratory infection were also studied.
Results The healthy subjects had a mean nasal MCC time of 11.7k3.8 (SD) minutes and no subject had a clearance of >60 minutes. The numbers of patients with nasal MCC <60 minutes and with grossly prolonged clearance (>60 minutes) are shown in Table I. The proportion of patients with perennial rhinitis, whether allergic or non-allergic, with or without asthma, who had grossly prolonged nasal MCC was not significantly different from the healthy controls. However, the three groups of patients with chronic infected rhinosinusitis (CIR) all had a significantly greater proportion of patients with nasal MCC >60 minutes than controls. In the group with CIR and bronchiectasis more patients had nasal MCC >60 minutes than had nasal MCC <60 minutes, and this group was also
Abnormal Nasal Mucociliary
79
Clearance in Patients with Rhinitis
significantly different (P
1.
The number of patients and >60 minutes
with
nasal mucociliary
NMCC <60 min
NMCC XT0
clearance
(NMCC)
times <60 minutes
Probability of difference from healthy subjects
min
(A-squared)
AR & normal chest AR & asthma NAR & normal chest NAR & asthma CIR & normal chest CIR & asthma CIR & CPSP
48 49 45 20 34 33 15
2 4 2 3 12 7 20
AR, allergic rhinitis; NAR, non-allergic CPSP, chronic purulent sputum production. Table
II. The mean nasal mucociliary minutes
clearance
NS Xi KS NS P
rhinitis;
CIR,
(NMCC)
times for subjects with clearance
Mean NMCC (min)
chronic
isD
Healthy subjects AR & normal chest AR & asthma NAR & normal chest NAR & asthma CIR & normal chest CIR & asthma CIR & CPSP
n=35 n=48 n=49 n=45 n=20 n=34 n=33
n=15
11.7k3.8 18.2k8.3 16.7kti.4 19.1k9.1 20.2k8.0 27.0-+_ 13.0 22.8k9.6 26.lrt_10.4
AR, allergic rhinitis; NAR, non-allergic chronic purulent sputum production.
rhinitis;
infected
rhinosinusitis;
Probabilip of difference healthy subjects (Mann-Whitney U test)
of <60
from
P
CIR,
chronic
infected
rhinosinusitis;
CPSP,
three groups with infected rhinitis. However, the mean nasal MCC time for patients with CIR was significantly longer (PcO.01; Mann-Whitney U test) than that of the patient groups with perennial rhinitis, except for the group with non-allergic rhinitis and asthma. Discussion Patients with perennial allergic, or non-allergic, rhinitis and to a greater extent those with chronic infected rhinosinusitis had prolonged nasal mucociliary
80
P. J. Stan@ et al.
clearance. Impairment of nasal MCC in patients with concomitant asthma was not significantly different from patients with no chest disease. However, nasal MCC was significantly more delayed in patients with chronic infected rhinosinusitis and bronchiectasis, 57% having nasal MCC >60 minutes, compared to other patients with infected or perennial rhinitis or normal subjects. All patients with infected rhinitis had similar upper respiratory clinical symptoms and signs, therefore the greater abnormalities of clearance seen in patients with concomitant bronchiectasis cannot be simply explained by differences in disease severity. Defective mucociliary transport can be considered to be due to abnormalities in its ciliary component, its mucus component or a combination of both components. None of the patients with grossly prolonged clearance had primary ciliary dyskinesia (any such patient having been excluded from the study) and previous work with a similar group of patients has shown that in vitro nasal ciliary beat frequency (CBF) and ciliary ultrastructure are within normal limits in the majority of patients with rhinitis and abnormal nasal MCC (Greenstone et al. 1983). However, in this study and in a study by Rutland and Cole (1981) CBF was statistically significantly slower, by approximately lo%, in patients with bronchiectasis although such a reduction in CBF may be of little biological significance. Nine of the ten patients in the latter study had nasal MCC (measured using the same saccharin method) of less than 60 minutes, therefore, this observed reduction in CBF is unlikely to be a major factor in producing the more severe abnormalities of clearance found in patients with bronchiectasis. Despite normal ciliary function in vitro, factors in mucus or serum could cause slowing of CBF or incoordination of cilia in vivo, or there may be loss of ciliated epithelium producing delayed MCC. Camner et al. (1973a) demonstrated a temporary defect in tracheobronchial MCC after influenza A virus infection which causes extensive destruction of ciliated epithelium (Hers et al. 1958). Reimer et al. (1978) examined the maxillary sinus mucosa of patients with chronic purulent sinusitis by scanning electron microscopy and found large areas of unciliated epithelium, although the remaining cilia exhibited a normal mucociliary wave frequency measured by an in vivo technique. Quantitative or qualitative differences in the bacterial flora between patients who have infected rhinitis with and without’ chronic lower respiratory tract sepsis might influence the degree of impairment of MCC and this aspect is at present under investigation. For eflicient mucociliary transport, mucus of optimal viscoelastic properties is necessary which, according to Dulfano and Adler (1975), is mucus of low viscosity and high elastic recoil. Infected mucus is more viscous than normal mainly due to increased DNA fibre content (Burgi 1973) and this may be a factor causing poor clearance in infected patients even if the cilia are beating normally. Majima et al. (1983), reported delayed nasal MCC in patients with chronic sinusitis and found that mucus from these patients was transported at a slower rate than normal mucus by the ciliated epithelium of an isolated bullfrog palate. However, there was no significant difference between the transport rate of mucus from patients with severely prolonged nasal MCC and that of mucus from patients
Abnormal Nasal Mucociliary
Clearance in Patients with Rhinitis
81
with only slightly delayed clearance. Mucus of low viscosity and low elasticity will also produce inefficient mucociliary transport. This may occur in patients with allergic, or non-allergic, non-infected rhinitis who characteristically have watery rhinorrhoea. Another factor of potential importance is uncoupling of the action of the cilia on overlying mucus by changes in the depth of the periciliary fluid layer (Proctor 1977). However, little is known about the factors controlling this fluid layer. The abnormal mucociliary clearance found in our patients is unlikely, therefore, to have a simple explanation, but is probably a combination of a change in mucus viscoelastic properties, alteration in the periciliary fluid layer, reduction in the number of cilia and possibly decreased motility of the cilia in vivo. Acknowledgements P.S. was supported by Berk Pharmaceuticals Ltd and R.W. by Janssen Pharmaceuticals Ltd. This work was supported by The Wellcome Trust and the National Fund for Research into Crippling Diseases. References Andersen, I., Camner, P., Jensen, P. L., Philipson, K. & Proctor, D. F. (1974) Nasal clearance in monozygotic twins. Am. Rev. resp. Dis. 110, 301-305. Burgi, H. (1973) Fibre systems in sputum. Bull. Physiopath. resp. 9, 191-196. Camner, P., Jarstrand, C. & Philipson, K. (1973a) Tracheobronchial clearance in patients with influenza. Am. Rev. resp. Dis. 108, 131-135. Camner, P., Mossberg, B. & Philipson, K. (1973b) Tracheobronchial clearance and chronic obstructive lung disease. Stand. J. resp. Dis. 54, 272-281. Dulfano, M. J. & Adler, K. B. (1975) Physical properties of sputum. VII. Rheologic properties and mucociliary transport. Am. Rev. resp. Dis. 112, 341-347. Greenstone, M. A., Stanley, P. J., Cole, P. J. & Mackay, I. S. (1984) Upper respiratory manifestations of primary ciliary dyskinesia. J. Laryngol. Otol. (in press). Greenstone, M. A., Stanley, P. J., MacWilliam, L., Dewar, A., Cox, T., Mackay, I. S. & Cole, P. J. (1983) Mucociliary function and ciliary ultrastructure in patients presenting with rhinitis to Brompton Hospital Nose Clinic. Eur. J. resp. Dis. 64, suppl. 128 (Part 2), 457-459. Hady, M. R. A., Shehata, 0. & Hassan, R. (1983) Nasal mucociliary function in different diseases of the nose. J. Laryngol. Otol. 97, 497-502. Hers, J. F. P., Masurel, N. & Mulder, J. (1958) Bacteriology and histopathology of the respiratory tract and lungs in fatal Asian influenza. Lancet 2, 1141-l 143. Lourenco, R. V., Loddenkemper, R. & Carton, R. W. (1972) Patterns of distribution and clearance of aerosols in patients with bronchiectasis. Am. Rev. resp. Dis. 106, 85&866. Mackay, I. S. (1979) Measurement of nasal airflow and resistance. J. R. Sot. Med. 72, 852-855. Majima, Y., Sakakura, Y., Matsubara, T., Murai, S. & Miyoshi, Y. (1983) Mucociliary clearance in chronic sinusitis; related nasal clearance and in vitro bullfrog palate clearance. Biorheology 20, 25 l-262. Pavia, D., Bateman, J. R. M. & Clarke, S. W. (1980) D ep osi‘t’ion and clearance of inhaled particles. Bull.
Proctor,
eur. Physiopath.
resp.
16, 335-366.
D. F. (1977) The upper airways. 1. Nasal physiology and defense of the lung. Am. Rev. resp. Dis. 115, 97-129. Reimer, A., von Mecklenburg, C. & Toremalm, N. G. (1978) The mucociliary activity of the upper respiratory tract. III. A functional and morphological study on human and animal material with special reference to maxillary sinus disease. Acta Otolaryngol. (Stockh.) suppl. 355, l-20.
P. J. Stanley et al. Rutland, J. & Cole, P. J. (1980) Non-invasive sampling of nasal cilia for measurement of beat frequency and study of ultrastructure. Lancet 2, 564-565. Rutland, J. & Cole, P. J. (1981) Nasal mucociliary clearance and ciliary beat frequency in cystic fibrosis compared with sinusitis and bronchiectasis. Thorax 36, 654-658. Stanley, P. J., MacWilliam, L., Greenstone, M. A., Daly, C. & Cole, P. J. (1984a) Prolonged nasal mucociliary clearance in smokers. Thorax 39, 239. Stanley, P. J., MacWilliam, L., Greenstone, M. A., Mackay, I. S. & Cole, P. J. (198413) Efficacy of a saccharin test for screening to detect abnormal mucociliary clearance. Br. J. Dis. Chest 78, 62-65.