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We hypothesized that differences in nasal nitric oxide (nNO) and fractional exhaled nitric oxide (Feno) relate to prognosis in primary ciliary dyskinesia (PCD).What is the relationship between baseline values and longitudinal evolution of nNO and Feno and ultrastructure, genotype, and respiratory infections in PCD?Prospective, longitudinal, single-center study in adults and children evaluated biannually for up to 10 years. We compared cross-sectional and longitudinal values of nNO and Feno in ultrastructural (inner dynein arm [IDA] and microtubular disorganization [MTD]) and genetic (CCDC39 and CCDC40) groups known to have worse pulmonary function with patients within the ultrastructural and genetic groups with a better prognosis. Linear mixed-effects models were used to evaluate longitudinal associations.One hundred forty-one patients with PCD underwent 1,014 visits. At enrollment, no differences were found in children in nNO or Feno between the IDA and MTD group and the other ultrastructural groups. In adults, nNO (P = .038) and Feno (P = .032) were significantly lower in the IDA and MTD group than in all other combined ultrastructural groups. Feno values were significantly lower in the CCDC39 and CCDC40 group than in the DNAH5 and DNAH11 combined genotype group (P = .033) and in all other genotypes (P = .032). The IDA and MTD group showed a significant decline in nNO with age (P .01) compared with other ultrastructural groups who showed stable levels. The CCDC39 and CCDC40 group showed the steepest decline in nNO over time (P .01) compared with all other genotypes. A higher nNO was associated with lower likelihood of any positive bacterial isolate from the lower respiratory tract (P = .008). Changes in Feno over time did not differ between structural groups or genotypes.Lower nNO in patients with PCD with genetic and ultrastructural changes associated with greater lung function decline may be related to worse prognosis, but whether a low nNO is causal needs further study. If lower nNO directly results in a poorer prognosis, strategies augmenting upper airway nitric oxide production may be worth evaluating.

Few data are currently available on the effects of aeroallergens in triggering respiratory symptoms in children. To evaluate the potential effects of daily outdoor aeroallergens loads on childhood admissions, in this case-crossover study, we analyzed data from 85 children hospitalized at the University Hospital of Pisa, Italy, for asthma or asthma-like symptoms without respiratory infection, between 2010 and 2019. Data were linked to outdoor allergens, temperature, nitrogen dioxide, and relative humidity observed during the same period. A 10-grains/m3 increase in the total aeroallergen concentration was associated with an increased risk of admission at lag 0 (OR = 1.054, 95% CI: 1.011–1.098), with a smaller effect at lag 1 (OR = 1.037, 95% CI: 1.008–1.067) and lag 2 (OR = 1.021, 95% CI: 1.003–1.039). Trends to larger effects were observed in children with sensitization to one or more aeroallergens (OR = 1.085, 95% CI: 1.004–1.173 at lag 0), in males (OR = 1.069, 95% CI: 1.009–1.132 at lag 0) and in older children (OR = 1.065, 95% CI: 1.007–1.127 at lag 0). Our study shows an association between increased outdoor allergens loads and asthma or asthma-like symptoms in children up to at least two days prior to hospitalization, suggesting that tracking aeroallergen counts may be useful to improve the management of respiratory allergic diseases.

Rationale: Genotype–phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but little is known about lung volume changes over time. Objectives: To investigate the evolution of st...

BACKGROUND: The diagnosis of primary ciliary dyskinesia (PCD) is difficult, and requires a combination of clinical features, nasal nitric oxide testing, cilia ultrastructural analysis by electron microscopy (EM), and genetics. A recently described cytoplasmic ultrastructural change termed “ciliary inclusions” was reported to be diagnostic of PCD; however, no supporting evidence of PCD was provided. In this study we sought to confirm, or refute, the diagnosis of PCD in subjects with “ciliary inclusions” on EM. METHODS: 6 subjects from 5 families with previous lab reports of “ciliary inclusions” on EMs of ciliated cells were identified and evaluated at a Genetic Disorders for Mucociliary Clearance Consortium site. We performed a detailed clinical history, nasal nitric oxide measurement, genetic testing including whole exome sequencing, and when possible, repeat ciliary EM study. RESULTS: Only 1 of 6 subjects had multiple and persistent clinical features congruent with PCD. No subject had situs inversus. Only 1 of 6 subjects had a very low nasal nitric oxide level. No “ciliary inclusions” were found in 3 subjects who had a repeat ciliary EM, and ciliary axonemal ultrastructures were normal. Genetic testing, including whole exome sequencing, was negative for PCD-causing genes, and for pathogenic variants in gene pathways that might cause “ciliary inclusions”, such as ciliary biogenesis. CONCLUSION: “Ciliary Inclusions”, in isolation, are not sufficient to diagnosis PCD. If seen, additional studies should be done to pursue an accurate diagnosis.