Deliberations of Studies Concerning Patients with Asthma, Aspirin Intolerance, and Nasal Polyps

Afzelius has suggested that the ultrastructural abnormalities seen in cilia can be separated into two groups: those with the specific defects he associates with the immotile cilia syndrome and those regarded as nonspecific. The occasional morphologic changes we have seen in our “triad” asthmatics and normal subjects would all be classified under his nonspecific category. Indeed, even most of the ultrastructural abnormalities noted in our patient with situs inversus and sinusitis were of this nonspecific type, but in addition, the dynein arms present on the microtubule doublets in this case occasionally were nub-like or fuzzy. Afzelius noted that when dynein arms were seen in his patients with Kartagener s syndrome, they were shorter than those found in normal cilia. Others also have noted these shortened arms.

In any case, it appears that cilia from patients with the triad of aspirin sensitivity, nasal polyposis, and asthma do not differ significantly from normal in the ultrastructural and functional parameters which have been assessed. Additionally, aspirin did not have any effect on the function of the cilia from the triad asthmatics. We also used arachidonic acid in the perfusate along with aspirin, since by blocking the cyclooxygenase pathway of arachidonic acid metabolism, aspirin might cause a shift to the lipoxygenase pathway with subsequent production of leukotrienes. The latter are believed to be important mediators of allergic and inflammatory reactions, but no change in the ciliary motility resulted. These experiments do not exclude the possibility that aspirin might interact with a serum factor to produce a ciliary inhibitory factor similar to that seen in cystic fibrosis.

Cystic fibrosis

Our patient with chronic sinusitis and situs inversus had findings compatible with the diagnosis of primary ciliary dyskinesia. Tbe electron micrographs of his cilia demonstrating that approximately 46 percent were abnormal in appearance correlated with the observation that approximately one half of his cilia did not evidence any apparent motility in vitro on initial examination. This does not explain, however, the abnormalities seen in the beating of the rest of the cilia (the stif£ slow, brush-like motion previously described above and noted as a type of abnormal motion seen in this syndrome), since the ultrastructural appearance of the rest of the cilia appeared normal. In addition, it is unknown whether the cilia with the abnormal ultrastructure were the same ones that appeared to lack motility in vitro. Rossman et al have demonstrated motion in cilia whifch appeared immobile through the use of a video motion analyzer attached to a phase contrast microscope. If one postulates that the cilia without apparent motion were the ones demonstrating ultrastructural defects, then one would have to suggest that other factors (eg, biochemical) might be involved in the abnormal motion evidenced by the ultrastruc-turally normal looking cilia. It has been suggested that nub-like dyneim arms are only partial pieces of dynein with an altered physiologic response; the complete outer dynein arms consist of three or four subunits (at least in mollusks). However, we found these nubs not only on this patients microtubules, but also on the microtubules of both normal control subjects and the triad patients.

Diagnosis and management of patients with Asthma, Aspirin Intolerance, and Nasal Polyps on video:

ATPase has been found to be a prominent structural component of dynein arms, and ATP is a major source of energy for ciliary movement.” The latter appears to involve an interaction between dynein arms and the adjacent peripheral doublet. In view of these considerations, Forrest et al tried stimulating ciliary activity of patients with the immotile cilia syndrome with ATP and ATPase and reported substantial enhancement of ciliary activity. We, likewise, obtained similar results with the cilia of our patient with situs inversus and sinusitis, although the increased motion was still abnormal. Although the effect of ATP might be expected, it is rather surprising that as large a molecule as ATPase would exert an effect on these intact cell preparations unless there is a membrane defect or another pathway by which the ATPase is transported into the cell. In any case, the capacity to maintain ciliary activity for prolonged periods in nasal respiratory epithelial cultures provides an opportunity for ongoing work on the effect of various relevant agents on human ciliary activity.

More information on this topic on our site:

Ultrastructural and Functional Studies of Cilia from Patients with Asthma, Aspirin Intolerance, and Nasal Polyps
Outcomes of Studies Concerning Patients with Asthma, Aspirin Intolerance, and Nasal Polyps