The ATS has published a new clinical practice guideline to help physicians diagnose primary ciliary dyskinesia (PCD), a rare, chronic disease that affects breathing beginning very early in life. The guideline appears online and in the June 15 American Journal of Respiratory and Critical Care Medicine.

PCD is a genetically heterogeneous disorder characterized by motile cilia dysfunction. Clinical manifestations of the disease include chronic upper and lower airway disease, left-right laterality defects and infertility. The severity of the disease varies, and children with PCD are often undiagnosed or misdiagnosed with other breathing problems.

“The clinical symptoms in PCD overlap with many other respiratory diseases in children, making it difficult for physicians to separate children with PCD from children with other common pulmonary issues, such as asthma or recurrent viral infections,” said guideline committee co-chair Adam J. Shapiro, MD, an assistant professor of pediatrics at McGill University and a pediatric pulmonologist at Montreal Children’s Hospital in Canada. “We hope that earlier diagnosis of PCD will result in earlier therapies to protect the respiratory system, which may improve long-term health outcomes.”

Valéry Lavergne, MD, MSc, of the University of Montreal Medical School’s Department of Microbiology, Infectious Diseases and Immunology, was the other co-chair of the guideline committee.
For over four decades, transmission electron microscopy (TEM) has been used to diagnose PCD on the basis of defects in the ciliary axoneme, the central core of the cilium. TEM is not highly sensitive or specific in diagnosing PCD, and several adjuvant diagnostic methods have emerged.

The ATS guideline committee of 30 clinical and scientific experts reviewed studies evaluating four different methods of diagnosing PCD. The committee rated the strength of study findings, along with the certainty of committee members’ recommendations, using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system.

To compare the effectiveness of the four methods, the committee considered the diagnostic reference standard TEM and/or genetic testing for known PCD mutations.

Against this reference standard, each method was evaluated based on its ability to diagnose patients with at least two of four key features that have recently been identified as characterizing PCD: 1) year-round, daily, productive (wet) cough; 2) year-round, daily, nonseasonal rhinosinusitis; 3) neonatal respiratory distress syndrome as term newborns; and 4) laterality defects (e.g., situs inversus totalis).
In these patients, the guideline committee suggests:

• Using an extended genetic panel (testing > 12 genes) as a diagnostic test over the reference standard of TEM and/or standard genetic panel (≤12 genes) testing (conditional recommendation, moderate certainty of evidence in test accuracy, but very low certainty in the overall evidence).
• Using nasal nitric oxide testing in patients over the age of five, who have tested negative for cystic fibrosis, over the reference standard (conditional recommendation, moderate certainty in test accuracy, but very low certainty in the overall evidence).
• Not using ciliary beat frequency analysis by digital high-speed videomicroscopy as a replacement diagnostic test over the reference standard (conditional recommendation, low certainty in the diagnostic accuracy of the test, and very low certainty in the overall evidence).
• Not using ciliary beat frequency as a diagnostic test over the reference standard (conditional recommendation, low certainty in the diagnostic accuracy of the test, and very low certainty in the overall evidence).

In the absence of a single definitive test for PCD, the committee recommends that a panel of tests be used to make the diagnosis. Even nasal nitric oxide testing, which when conducted properly in appropriate patients appears to have diagnostic accuracy equivalent to TEM and/or genetic testing, should not replace standard tests in all cases, according to the guideline committee.

“Unfortunately, no single test can diagnose all cases of PCD, but the most feasible and accurate tests at present are nasal nitric oxide and genetic testing,” Dr. Shapiro said. “Some patients will need to visit PCD specialty centers to have the proper diagnostic testing performed, and physicians will need to pursue appropriate diagnostic testing on a case-by-case basis, depending upon the available PCD tests and clinical resources in each institution.”