Clinical expressions of immotile cilia syndrome.

To date three distinct morphologic types of immotile cilia disorder in man have been recognized. Patients with the disorder have variable clinical manifestations of disease of the upper and lower respiratory tract. Twenty-one patients with immotile cilia syndrome have been evaluated from the standpoint of history, clinical presentation, radiologic changes, pulmonary function tests, and mucociliary clearance. The results have been compared to the pathologic changes noted on ultrastructural examination of the cilia. Although clinical severity does not correlate with the type of abnormality found, a profile of clinical signs and symptoms suggestive of immotile cilia syndrome has emerged. The triad of productive cough, sinusitis, and otitis was a consistent finding in all. Situs inversus occurred in only half of the patients.

Aerosol therapy with Sch 1000. Short-term mucociliary clearance in normal and bronchitic subjects and toxicology in normal subjects.

The anticholinergic bronchodilator drug, Sch 1000, was administered as an aerosol by a metered-dose inhaler (200 microgram) to six normal and six bronchitic subjects. The short-term effect on mucociliary clearance was assessed and compared to a placebo (propellant and dispersal agent) in a double-blind crossover study. Mucociliary clearance in the normal group was significantly faster with administration of Sch 1000 than with placebo (P less than 0.01). There was no significant difference between the effects of administration of Sch 1000 and placebo on mucociliary clearance in the bronchitic group. Pulmonary function was significantly increased by therapy with Sch 1000 (as compared to administration of placebo) in the bronchitic group for two hours (P less than 0.05) and in the normal group for one hour (P less than 0.05). In another study, 12 normal subjects inhaled aerosols containing 40 microgram of placebo or 400 microgram of Sch 1000 from metered-dose inhalers on separate days in a randomized double-blind fashion. A significant sustained improvement in pulmonary function (P less than 0.05) and a transient fall in diastolic blood pressure were observed after administration of Sch 1000.

Ultrastructural features of respiratory cilia in cystic fibrosis.

The respiratory cilia of nine patients with cystic fibrosis were examined by electron microscopy. In contrast to patients with "immotile cilia syndrome," the cilia from the patients with cystic fibrosis contained dynein arms and radial spokes. A low percentage of abnormal cilia were detected in all nine patients, but, except for the occurrence of rippled cilia in these patients, the alterations were similar both in morphologic terms and incidence to alterations in a control group of patients with chronic bronchitis. Lesions included compound cilia, excess cytoplasmic matrix, and an abnormal number or arrangement of microtubular doublets. Patients suffering from cystic fibrosis do not exhibit ultrastructural ciliary alterations characteristic of immotile cilia syndrome.

The oviductal cilia and Kartagener's syndrome.

Women who have Kartagener's syndrome (primary ciliary dyskinesia) may or may not be fertile. The bronchial mucociliary clearance is reduced markedly in most of these women; this has led investigators to the conclusion that the cilia in the respiratory tract are immotile, and that "beating cilia may have no indispensable role in the female reproductive tract." Yet motile cilia are considered by many workers to be essential for normal ovum transport. More recently, bizarre ciliary motion has been described in the respiratory cilia of Kartagener's women. Our hypothesis was that the dyskinetic ciliary activity (or immotility) would be the same in both the respiratory and reproductive tracts and thus explain the fertility (or lack of it) in Kartagener's women. This report shows an identical ultrastructure and absolute immotility of cilia in both the respiratory tract and reproductive tract of a woman with Kartagener's syndrome who has never conceived. From this concordance, we suggest that the fertility of Kartagener's women is explained by the dyskinetic motion of oviductal cilia, and that the ciliated endosalpinx is essential for human reproduction.

Middle ear cilia activity as a determinant of tympanostomy tube placement.

Three hundred and twenty-six patients with diagnoses of serous otitis media--or mucoid otitis media--were reviewed for the presence or absence of middle ear cilia activity. This study strongly suggests that if active cilia can be observed, ventilating tubes are not needed. This easily observed activity in the anterior-inferior quadrant offers the otolaryngologist an accurate tool for determination of the future health of the middle ear.

Scanning electron microscopic examination of nonbeating cilia.

When cilia stop beating, their role in moving mucus ceases, but it is uncertain if nonmotile cilia preserve their external architecture and are thus capable of maintaining an additional role of retarding microbial access to the cell. Cilia of chicken embryo tracheal organ cultures were observed until their activity stopped. When examined with scanning electron microscopy, ciliary axonemes did not appear to differ significantly from normally functioning cilia when observed at lower magnifications. Since their density can remain essentially unchanged, nonbeating cilia may still have a role in protecting respiratory membrane from toxic microorganisms.

Mucociliary function in children with secretory otitis media.

Mucociliary clearance of the nasal meatus and the middle ear cavity was measured by a radioisotopic method using 99mTc-labelled human serum albumin as a tracer substance. In the patients with secretory otitis media the tracer did not move in either ear indicating a lack of mucociliary clearance. Lowered nasal mucociliary transport velocity was found in 31 of the 46 child patients with recurrent or chronic respiratory infections. 11 from 31 patients (35%) suffered from recurrent otitis media and 19 (62%) from secretory otitis media. Only one patient of the 15 cases with normal transport velocity had secretory otitis media. It seems that primarily or secondarily impaired mucociliary function plays an important role in the pathophysiology of secretory otitis media.

Primary and secondary ciliary dyskinesia.

It has recently been shown that patients with Kartagener's triad and also some subjects with similar symptoms, but without situs inversus, have a congenital abnormality of cilia as an explanation for their chronic airway symptoms; this disease has been named "the immotile-cilia syndrome" or more correctly "primary ciliary dyskinesia". Studying 27 such patients, we have found daily nose blowings since birth, chronic-recurrent sinusitis, and chronic secretory otitis media highly characteristic features. The frequency of common colds was not increased, and most patients did not suffer from repeated episodes of acute purulent otitis media. The number of ciliated cells with immotile cilia was increased, but only a single patient had completely immotile cilia; also the degree of asynchrony within the single ciliated cell was increased. Electron microscopy showed a decreased number of dynein arms in some patients, and abnormal arrangement of microtubules in others. Some patients, however, had normal ultrastructure, and this appeared to be associated with a hyperfrequent beating pattern. At least three subgroups of patients with primary ciliary dyskinesia can be delineated based on the motility-ultrastructure studies. Bacterial infection tends to reduce the number of ciliated cells with motile cilia, and viral infection (common cold) gives a very marked and long-lasting reduction in the number of ciliated cells. This may account for some otherwise unexplainable subchronic symptoms from nose and throat.

The nasal mucosa in immunodeficiency. Surface morphology, mucociliary function and bacteriological findings in adult patients with common variable immunodeficiency or selective IgA deficiency.

Twenty-two adult patients suffering from common variable immunodeficiency (CVID) and sixteen patients with selective IgA deficiency were examined with regard to the mucocilliary function of the nose. The surface structures of the nasal mucosa, e.g. cell distribution and degree of destruction and metaplasia, were judged from scanning electron microscopy of nasal biopsies. Bacteria were isolated from nasopharyngeal swabs. The results of the clinical and morphological investigations were analysed with regard to the duration of the disease and possible benefit of adequate prophylaxis with immunoglobulin. It was found that patients with CVID had a slower mucociliary transport rate and more extensive mucosal damages than patients with selective IgA deficiency. Most likely these alterations were due to repeated infections as patients who had had few infections or adequate immunoglobulin prophylaxis (CVID patients) had better mucociliary function and showed less extensive mucosal changes. Potentially pathogenic bacteria in the nasopharynx were found in equal numbers in both patient groups.

Activation of the impaired nasal mucociliary function. A preliminary clinical study.

The effect of HR-6 solution containing adenosine triphosphate 10 mg/ml on the impaired nasal mucocililary function in 13 patients was studied. The nasal mucociliary function measured with the radioisotopic method using 99Tc-labelled human serum albumin as a tracer substance was markedly impaired in all patients. The patients had had symptoms of upper and/or lower respiratory tract infections for 8 1/2 years, on the average. The nasal mucociliary function ranged from 0 to 5.0 mm/minute, mean 2.0 mm/minute. In this single dose study the test drug improved nasal mucociliary function by at least 1.4 mm/minute in 77% of the patients and by at least 2.8 mm/minute in 54% of the patients. This preliminary study indicates the need for further examinations with the HR-6 in patients with impaired mucociliary function.

Cilia injury during virus infection in chickens.

The reduction of mucociliary clearance in the Newcastle disease virus-B infected nasal turbinate in chickens is mainly due to ciliary pathology, decrease of the number of cilia and of the ciliary beat frequency.

[Ciliated epithelium of the Fallopian tube in women. An ultrastructural study (author's transl)]. / Epithélium cilié de la trompe de Fallope chez la femme. Etude ultrastructurale.

The steps in the ultrastructural changes that occur in new cilia formation in tubal epithelium have been well demonstrated in animals. In women, it is difficult to show cilia growing again and some authors deny that new growth occurs. Transmission electron microscopy studies on 32 specimens have shown that human new growth of cilia does occur. It arises in the midst of a cellular population which has as its characteristic a cytoplasm that is more clear than those of the neighbouring cells. Different ultrastructural aspects can be described. They resemble those that have been demonstrated in different animal species. On the other hand no mitoses have been shown. We will study the correlations between plasma hormone levels, the numbers of tissue receptors and the appearance of these clear cells in another article.

[Incidence of ciliary beats in nasal cells obtained from smears. Study of 40 patients of whom 28 were children with respiratory pathology]. / Fréquence du battement des cils des cellules nasales obtenues par frottis. Etude chez 40 patients dont 28 enfants atteints de pathologie respiratoire.

Disturbance of ciliary function are considered as a significant factor in the outcome of chronic respiratory afflictions. Thanks to a simple method of stroboscopic lighting, the ciliary beat frequency was studied on 40 nasal mucus smears obtained by swabbing in 28 children and 12 adults with chronic respiratory failure or recurrent disease. The 28 children were divided into three groups: group A (n = 10), pulmonary disease (broncho-pneumonia); group B (n = 3), Kartagener syndrome; group C (n = 15) pure otorhinolaryngological (ORL) disease (rhino-opharyngitis, sinusitis, otitis). Twelve adults with chronic ORL pathology (vaso-motor rhinitis) made up group D. A cytological control was carried out on each smear and showed the presence of ciliated cells in 92.5% of samples. In three group B cases (Kartagener's syndrome) no ciliary movement was observed. The results in groups A (9.3 +/- 1.46 Hz) and C (8.98 +/- 2.23 Hz) show that the level of respiratory infection (pulmonary or ORL) did not influence the ciliary beat frequency (p greater than 0.05). On the other hand, there was a significant difference (p less than 0.001) between the beat frequency in the group of children in group A (9.3 +/- 1.46 Hz) and C (8.98 +/- 2.23 Hz) and those of adults in group D (11.32 +/- 1.89 Hz). Two hypotheses might explain these facts: The existence of a differing physiological response in children and adults. Different mechanisms during chronic ORL infections in adults (vasomotor phenomena) and in the child (bacterial infection). The average frequencies measured were comparable to those previously published in human respiratory cilia using other methods.(ABSTRACT TRUNCATED AT 250 WORDS)