Objective: To evaluate the relationship between ciliary ultrastructure/genotype and prevalence of neonatal respiratory distress in primary ciliary dyskinesia (PCD). Study Design: This was a retrospective analysis from a multicenter, prospective study of children and adults with PCD. Participants were classified by ultrastructural defect associated with their diagnostic genetic variants: 1) outer dynein arm defect alone (ODA), 2) outer plus inner dynein arm defect (ODA/IDA), 3) inner dynein arm defect with microtubular disorganization (IDA/MTD), 4) DNAH11 (encodes ODA protein but has normal ultrastructure), and 5) normal/near normal/other. The likelihood of neonatal respiratory distress between ultrastructure groups or genotypes was evaluated by multivariate analysis using logistic regression, controlled for age, gender, race, and variant type. Similar analysis was performed within individual genotypes to assess association of neonatal respiratory distress with the presence of 2 loss-of-function variants. Results: Of the 455 participants analyzed, 305 (67.0%) reported neonatal respiratory distress. The odds ratio for neonatal respiratory distress in the DNAH11 group was significantly lower (OR 0.35, 95% CI 0.16-0.76) compared to neonatal respiratory distress in the ODA group. Within the DNAH5 group, those with 2 loss-of-function variants were more likely to have neonatal respiratory distress compared to those with possible residual function variants (OR 3.06, 95% CI 1.33-7). Conclusion: Neonatal respiratory distress is less common in those with DNAH11 variants, thus a high index of suspicion should remain for PCD in the absence of neonatal respiratory distress.

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Background: Individuals with cystic fibrosis (CF) and fungal airway infection may present with fungal bronchitis, allergic bronchopulmonary aspergillosis (ABPA) or may appear unaffected despite fungal detection. We sought to characterize people with CF with frequent detection of fungi from airway samples and determine clinical outcomes. Methods: This retrospective study included individuals with CF with ≥ 4 lower airway cultures over a 2-year baseline period and ≥ 2 years of follow-up. We defined two groups: ≤ 1 positive fungus culture (rare) or ≥ 2 positive cultures during baseline (frequent). Clinical characteristics and outcomes were determined. Results: Between 2004-2016, 294 individuals met inclusion with 62% classified as rare and 38% as frequent fungi during baseline. Median follow-up was 6 years (range 2-9 years). Aspergillus fumigatus was the most common fungal species detected. Individuals with frequent fungi were older (13.7 vs. 11.7 yrs, p = 0.02) and more likely to have Stenotrophomonas maltophilia (35% vs 17%, p < 0.001) at baseline, but did not differ in lung function or ABPA diagnosis. During follow-up, those with frequent fungi were more likely to have chronic P. aeruginosa and S. maltophilia. Individuals with ABPA and frequent fungi had the highest rates of co-infection and co-morbidities, and a trend towards more rapid lung function decline. Discussion: Fungal infection in CF was associated with frequent P. aeruginosa and S. maltophilia co-infection even in those without ABPA. Individuals with frequent fungi and ABPA had worse outcomes, highlighting the potential contribution of fungi to CF pulmonary disease.