In reference to high yield technique to diagnose immotile cilia syndrome: A suggested algorithm

I read with grave concern the article by Josephson et al. published in The Laryngoscope (2010;120(Suppl 4):S240. High Yield Technique to Diagnose Immotile Cilia Syndrome: A Suggested Algorithm) and am compelled to respond and point out the fallacy of its conclusion. As a researcher with over 30 years of experience in the diagnosis of primary ciliary dyskinesia (PCD) and intimate familiarity with the literature on this subject, I can unequivocally state that any effort to make a specific diagnosis of PCD in the absence of electron microscopic evaluation of cilia and/or genetic testing of known mutations is erroneous. A major flaw in this report is its assertion that light microscopic evidence of ciliary activity alone is sufficient to exclude the diagnosis of PCD. Although the authors provide some qualifying verbiage that this evaluation may occur in concert with electron microscopic analysis, this inevitably will be read that the visualization of beating cilia in a biopsy from a patient being evaluated for possible PCD precludes the need for confirming EM and/or genetic studies. Such a conclusion would be patently false and without merit. Our laboratory has for many years collected nasal biopsies from patients suspected of having PCD. We routinely perform light microscopic studies on these specimens that include analysis of ciliary beat frequency (CBF) and ciliary kinetics. The observations made on such specimens provide support for diagnoses of PCD, but it is abundantly clear based on our comprehensive EM and genetic studies, that these characteristics alone cannot be used to make a definitive diagnosis of PCD. Caregivers embracing this approach to the diagnosis of PCD as described by these authors run the very real danger of pronouncing false negatives. Although our laboratory and others have demonstrated that there often exists a pattern of reduced CBF and a dysfunctional modification of ciliary kinetics in PCD, there also exist subpopulations of well-documented PCD patients with vigorous CBF and seemingly normal kinetics but with unequivocal ultrastructural and/or genetic confirmation of PCD. Moreover, recent research studies have further confirmed that cilia from patients with certain of the known PCD mutations exhibit normal if not hyperkinetic beat. It also is unfortunate that the authors entitled their report using the term ‘‘immotile cilia syndrome,’’ which was discarded 30 years ago in favor of PCD and more correctly describes this syndrome in terms of its typical presentation. Of greater concern than this however, are the authors’ specific promotion of this approach to the diagnosis of PCD in children. There have been great advances in the diagnosis and treatment of PCD over the last 30 years, and one of the great truths that has emerged is that early diagnosis of PCD in children creates an environment for promoting patient education and ongoing optimal medical management. I am most fearful that the simplistic approach to diagnosis endorsed by these authors will result in missed diagnoses among young patients who would be the most important beneficiaries of accurate diagnoses. Please feel free to forward this correspondence to the authors. I would be delighted for an opportunity to consult with them further on this topic. Thank you very much for your attention.