Owora, Arthur Hamie

Abstract Primary ciliary dyskinesia (PCD) results from mutations in over 50 genes that affect motile cilia (PMID: 29905515). PCD incidence is at least 1:7600 (PMID: 35051411). Asthma may be a PCD comorbidity (PMID: 36431268); and antigen stasis on the airway surface in PCD may predispose to asthma (PMID: 3831866). Methods. We analyzed the association between PCD and asthma in children ≤ 18 years old in two large electronic health record (EHR)-based databases: the Indiana Network for Patient Care Research (INPCR) cohort of 20 million EHRs and, in a validation cohort, TriNetX, with 112 million EHRs. We needed to address two issues. First, there is no ICD 10 code for PCD. Secondly, clinicians may confuse asthma and PCD in assessment. Therefore, we analyzed two diagnoses that, together, are unlikely to occur together in the absence of PCD: bronchiectasis (ICD10:J47) and situs inversus totalis (Q89.3) together (B-SIT). We asked whether subjects with B-SIT also had an asthma diagnosis ( ICD10 J45). We matched cases to controls, 1:3 in INPCR; and 1:1 in TriNetX, controlling for age, sex and race. We used conditional logistic regression adjusted for the matching strategy. For INPCR, we performed a conditional exact test: numbers were too small for adjusted models. This study was approved by the Indiana University and Case Western Reserve University IRBs. Results. In the initial INPCR study, 100% of children with B-SIT had an asthma diagnosis (p < 0.001). In the TriNetX validation cohort (Matched 1:1, n = 115 each), 84 children with B-SIT had asthma and 31 did not; in the controls, 12 had asthma and 103 did not (p = 2.2 x 10-16). The adjusted OR for B-SIT patients having asthma was 22.26 (95%CI: 10.80 – 45.91; p <0.001). Discussion. In two large EHR data sets, we found that most children with likely PCD (B-SIT) had a diagnosis of asthma. Local antigen stasis in PCD could contribute to the asthma phenotype in PCD, or perhaps even to asthma among patients heterozygous for PCD genes (PMID: 38457400). Additional studies are needed to understand the immunology, and this study is that it will need to be validated prospectively using airway reactivity testing after drug with-hold. In summary, children with PCD may need evaluation for airway reactivity. Further, providers should be alert to whether there are cardinal features of PCD among any of the children cared for with a diagnosis of asthma.

This case-control study uses electronic health record data to assess the association between primary ciliary dyskinesia and asthma in children.