Chest
Volume 132, Issue 3, September 2007, Pages 966-976
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ORIGINAL RESEARCH
PRIMARY CILIARY DYSKINESIA
Pulmonary Radioaerosol Mucociliary Clearance in Diagnosis of Primary Ciliary Dyskinesia

https://doi.org/10.1378/chest.06-2951Get rights and content

Background

Methods relying on nasal ciliary motility for the diagnosis of primary ciliary dyskinesia (PCD) are often hampered by secondary ciliary dyskinesia. A functional test for pulmonary mucociliary clearance, which is not influenced by secondary nasal ciliary defects, would be a valuable tool in a PCD workup.

Methods

The diagnostic validity and repeatability of a pulmonary radioaerosol mucociliary clearance (PRMC) test for the diagnosis of PCD was assessed in the following three sequentially performed substudies: (1) a preliminary cross-sectional study of PRMC in patients with known PCD; (2) a prospective blinded trial of patients referred for suspicion of PCD; and (3) an implementation study of PRMC as a routine method used in a PCD workup. PRMC was studied after 99mTc-albumin colloid aerosol inhalation, and the results were compared to (1) the results of nasal ciliary motility studies, (2) ciliary ultrastructure, and (3) the final clinical diagnosis. The repeatability of PRMC was assessed in 14 patients.

Results

A total of 95 patients, 5 to 74 years of age, were included in the study (57 patients in whom PCD was diagnosed, 26 non-PCD patients, and 12 patients referred for PCD workup without a conclusive workup result). In substudy 1, 14 of 15 patients with known PCD showed impaired PRMC; the results were inconclusive in 1 patient. In substudy 2, among 59 patients referred for PCD workup PRMC test results, compared to nasal ciliary motility, showed a sensitivity of 88% and a specificity of 100%. In substudy 3, among 21 patients referred for PCD investigation who were included in a routine PCD workup after PRMC implementation, 71% of PRMC test results were in alignment with nasal ciliary motility. Repeatability of interpretation was seen in 13 of 14 cases. A conclusive PRMC after only one test was found in 81 of 95 patients (85%).

Conclusion

PRMC is a noninvasive functional test for total tracheobronchial mucociliary clearance with a high sensitivity and specificity for PCD, a high rate of conclusive results after only one test and a further ability to separate PCD from focal pulmonary mucociliary defects.

Section snippets

Aim

The aim of this three-part study was as follows: (1) to describe PRMC in a preliminary study by testing it on a population of patients with known PCD; (2) following that, to assess the diagnostic validity (ie, sensitivity, specificity, and positive and negative predictive values) in patients referred for a PCD workup in a blinded trial by testing PRMC against nasal ciliary motility studies; and (3) after acceptance of PRMC as a valid method based on the results of substudies 1 and 2, to

Patients

We studied 95 patients, all of whom were referred to the National PCD Centre in Copenhagen for workup due to a clinical suspicion of PCD. Prior to study inclusion, cystic fibrosis was ruled out. Tests were performed at least 4 to 6 weeks after the occurrence of an acute upper or lower respiratory tract infection. In case of inconclusive tests, repeated testing was performed after treatment with antibiotics for 6 weeks. PRMC was allowed to be performed up to three times and a ciliary motility

Results

A total of 95 patients (age range, 5 to 74 years) were included in this three-part study. Among the 95 patients, the 15 patients from substudy 1 were already known to have PCD, in substudy 2 PCD was diagnosed in an additional 36 patients, and in substudy 3 PCD was diagnosed in an additional 6 patients. PCD was ruled out in 26 patients in substudies 2 and 3. Hence, the study population consisted of 57 patients with a confirmed diagnosis of PCD, 26 non-PCD patients, and 12 patients who had been

Discussion

This is the first study of PRMC comprising a larger population of PCD patients and also the first study in which PRMC has been applied in a routine clinical setting for diagnosing PCD. Our study of PRMC studies applied to known PCD patients confirmed PRMC to be a highly valid functional test for detecting impaired tracheobronchial clearance in patients in whom PCD had previously been diagnosed by the presence of abnormal nasal ciliary motility and ultrastructure.

In the prospective blinded trial

Conclusion

In this study, we have evaluated PRMC as a functional test for mucociliary clearance in patients suspected of having PCD. PRMC is at present the only method for testing the mucociliary function in ciliated parts of the lower airways of an individual and is not influenced by local nasal secondary mucociliary defects.

We conclude from this study, that PRMC (1) has a high diagnostic validity and repeatability of interpretation in the diagnosis and exclusion of PCD in a selected group of patients

Appendix

The procedure for the calculation of reference values for PRMC and RSDs based on a multiple regression model5 is as follows: LR=k0+(k1×age)+(k2×sex)+(k3×PI)±SD Predicted LR2(%)=66.71+(-0.08×age)+(-2.22×sex)+(26.89×PI)±9.65 k0=66.71;k1=-0.08;k2=-2.22(sex:1=male,2=female);k3=26.89;SDLR2=9.65

ACKNOWLEDGMENT

We thank the bioanalytical technologists (especially Ulla Kernchen and Lene Højby) in the Department of Clinical Physiology and Nuclear Medicine for their help in performing the radioaerosol clearance studies; and bioanalytical technologist Marianne Moller Andersen in the Department of Pediatrics for performing the ciliary function analysis.

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Cited by (0)

Dr. Marthin was supported during this work by a grant from SanCop Foundation.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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