Do Causes Influence Functional Aspects and Quality of Life in Patients with Nonfibrocystic Bronchiectasis?

Background: The denomination of noncystic fibrosis bronchiectasis (NCFB) includes several causes, and differences may be expected between the patient subgroups regarding age, comorbidities, and clinical and functional evolution. This study sought to identify the main causes of NCFB in a cohort of stable adult patients and to investigate whether such conditions would be different in their clinical, functional, and quality of life aspects. Methods: Between 2017 and 2019, all active patients with NCFB were prospectively evaluated searching for clinical data, past medical history, dyspnea severity grading, quality of life data, microbiological profile, and lung function (spirometry and six-minute walk test). Results: There was a female predominance; mean age was 54.7 years. Causes were identified in 82% of the patients, the most frequent being postinfections (n = 39), ciliary dyskinesia (CD) (n = 32), and chronic obstructive pulmonary disease (COPD) (n = 29). COPD patients were older, more often smokers (or former smokers) and with more comorbidities; they also had worse lung function (spirometry and oxygenation) and showed worse performance in the six-minute walk test (6MWT) (walked distance and exercise-induced hypoxemia). Considering the degree of dyspnea, in the more symptomatic group, patients had higher scores in the three domains and total score in SGRQ, besides having more exacerbations and more patients in home oxygen therapy. Conclusions: Causes most identified were postinfections, CD, and COPD. Patients with COPD are older and have worse pulmonary function and more comorbidities. The most symptomatic patients are clinically and functionally more severe, besides having worse quality of life.

Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules.

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.

Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel RPGR Variant and Possible Modifier Gene.

We report a novel RPGR missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the RPGR variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The pathogenicity of the variant on the RPGR protein was evaluated by in vitro studies transiently transfecting the mutated RPGR gene, and immunofluorescence analysis on nasal brushing samples. Whole-exome sequencing was conducted to identify potential modifier variants. In vitro studies showed that the mutated RPGR protein could not localise to the cilium and impaired cilium formation. Accordingly, RPGR was abnormally distributed in the siblings' nasal brushing samples. In addition, a missense variant in CEP290 was identified. The concurrent RPGR variant influenced ciliary mislocalisation of the protein. We provide a comprehensive characterisation of motile cilia in this XLRP family, with only the proband presenting PCD symptoms. The variant's pathogenicity was confirmed, although it alone does not explain the respiratory symptoms. Finally, the CEP290 gene may be a potential modifier for respiratory symptoms in patients with RPGR mutations.

The primary ciliary dyskinesia-related genetic risk score is associated with susceptibility to adult-onset asthma.

BACKGROUND: Disturbance of mucociliary clearance is an important factor in the pathogenesis of asthma. We hypothesized that common variants in genes responsible for ciliary function may contribute to the development of asthma with certain phenotypes. METHODS: Three independent adult Japanese populations (including a total of 1,158 patients with asthma and 2,203 non-asthmatic healthy participants) were studied. First, based on the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/), we selected 12 common single-nucleotide polymorphisms (SNPs) with molecular consequences (missense, nonsense, and 3'-untranslated region mutation) in 5 primary ciliary dyskinesia (PCD)-related genes and calculated a PCD-genetic risk score (GRS) as a cumulative effect of these PCD-related genes. Second, we performed a two-step cluster analysis using 3 variables, including PCD-GRS, forced expiratory volume in 1 second (%predicted FEV1), and age of asthma onset. RESULTS: Compared to adult asthma clusters with an average PCD-GRS, clusters with high and low PCD-GRS had similar overall characteristics: adult-onset, female predominance, preserved lung function, and fewer features of type 2 immunity as determined by IgE reactivity and blood eosinophil counts. The allele frequency of rs1530496, a SNP representing an expression quantitative trait locus (eQTL) of DNAH5 in the lung, showed the largest statistically significant difference between the PCD-GRS-High and PCD-GRS-Low asthma clusters (p = 1.4 x 10-15). CONCLUSION: Genes associated with PCD, particularly the common SNPs associated with abnormal expression of DNAH5, may have a certain influence on the development of adult-onset asthma, perhaps through impaired mucociliary clearance.

Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.

Nasal nitric oxide (nNO) is low in most patients with primary ciliary dyskinesia (PCD). Decreased ciliary motion could lead to antigen stasis, increasing oxidant production and NO oxidation in the airways. This could both decrease gas phase NO and increase nitrosative stress. We studied primary airway epithelial cells from healthy controls (HCs) and patients with PCD with several different genotypes. We measured antigen clearance in fenestrated membranes exposed apically to the fluorescently labeled antigen Dermatophagoides pteronyssinus (Derp1-f). We immunoblotted for 3-nitrotyrosine (3-NT) and for oxidative response enzymes. We measured headspace NO above primary airway cells without and with a PCD-causing genotype. We measured nNO and exhaled breath condensate (EBC) H2O2 in vivo. Apical Derp1-f was cleared from HC better than from PCD cells. DUOX1 expression was lower in HC than in PCD cells at baseline and after 24-h Derp1-f exposure. HC cells had less 3-NT and NO3- than PCD cells. However, NO consumption by HC cells was less than that by PCD cells; NO loss was prevented by superoxide dismutase (SOD) and by apocynin. nNO was higher in HCs than in patients with PCD. EBC H2O2 was lower in HC than in patients with PCD. The PCD airway epithelium does not optimally clear antigens and is subject to oxidative and nitrosative stress. Oxidation associated with antigen stasis could represent a therapeutic target in PCD, one with convenient monitoring biomarkers.NEW & NOTEWORTHY The PCD airway epithelium does not optimally clear antigens, and antigen exposure can lead to NO oxidation and nitrosative stress. Oxidation caused by antigen stasis could represent a therapeutic target in PCD, and there are convenient monitoring biomarkers.

[Genetic analysis of a fetus with Meckel syndrome due to variants of TMEM67 gene].

OBJECTIVE: To carry out prenatal diagnosis for a fetus with Meckel syndrome (MKS) and explore its genetic basis. METHODS: A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c.296delA (p.Lys99SerfsTer6) and c.1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.296delA variant was predicted to be pathogenic (PVS1+PM2_Supporting+PP4), whilst the c.1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4). CONCLUSION: The c.296delA and c.1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.

Magnetic Resonance Imaging of Pulmonary and Paranasal Sinus Abnormalities in Children with Primary Ciliary Dyskinesia Compared to Children with Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z-score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF (r = -0.523 and -0.687; P < 0.01) and with lung clearance index in children with CF (r = 0.650; P < 0.001) but not in PCD (r = 0.353; P = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD (r = 0.075-0.157; P = 0.557-0.788) but correlated moderately with MRI morphology score in CF (r = 0.437; P < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Stepwise genetic approach for the diagnosis of primary ciliary dyskinesia in highly consanguineous populations.

BACKGROUND: The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations. METHODS: Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed. RESULTS: Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones. CONCLUSIONS: In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.

The genetic framework of primary ciliary dyskinesia assessed by soft computing analysis.

BACKGROUND: International guidelines disagree on how best to diagnose primary ciliary dyskinesia (PCD), not least because many tests rely on pattern recognition. We hypothesized that quantitative distribution of ciliary ultrastructural and motion abnormalities would detect most frequent PCD-causing groups of genes by soft computing analysis. METHODS: Archived data on transmission electron microscopy and high-speed video analysis from 212 PCD patients were re-examined to quantitate distribution of ultrastructural (10 parameters) and functional ciliary features (4 beat pattern and 2 frequency parameters). The correlation between ultrastructural and motion features was evaluated by blinded clustering analysis of the first two principal components, obtained from ultrastructural variables for each patient. Soft computing was applied to ultrastructure to predict ciliary beat frequency (CBF) and motion patterns by a regression model. Another model classified the patients into the five most frequent PCD-causing gene groups, from their ultrastructure, CBF and beat patterns. RESULTS: The patients were subdivided into six clusters with similar values to homologous ultrastructural phenotype, motion patterns, and CBF, except for clusters 1 and 4, attributable to normal ultrastructure. The regression model confirmed the ability to predict functional ciliary features from ultrastructural parameters. The genetic classification model identified most of the different groups of genes, starting from all quantitative parameters. CONCLUSIONS: Applying soft computing methodologies to PCD diagnostic tests optimizes their value by moving from pattern recognition to quantification. The approach may also be useful to evaluate atypical PCD, and novel genetic abnormalities of unclear disease-producing potential in the future.

Quantification of Mastoid Air Cells and Opacification of the Middle Ear in Primary Ciliary Dyskinesia.

OBJECTIVE: To evaluate pneumatization and opacification of the temporal bone on computed tomography (CT) images in patients with primary ciliary dyskinesia (PCD). STUDY DESIGN: Retrospective case-control study. SETTING: Tertiary referral center. PATIENTS: Fifteen patients with PCD (30 ears) and 45 age-matched individuals without PCD (90 ears) as controls. INTERVENTION: Diagnostic only. MAIN OUTCOME MEASURES: Quantification of mastoid air cells in the PCD and control groups and comparison between them. Degree of middle ear opacification on CT images of the temporal bone in the PCD group. RESULTS: The volume of the mastoid air cells was 30% smaller in the PCD group than in the control group ( p < 0.05). The suppression ratio, which is defined to indicate how much the average volume of mastoid air cells in the PCD group is suppressed relative to the control group, was 64% lower in the PCD group ( p < 0.05). Opacification was noted in 47% of the mastoid air cells and 63% of the tympanic cavity on CT images of the temporal bone in the PCD group, which were significantly higher frequencies than in the control group (1.1% and 1.1%, respectively). CONCLUSIONS: Compared with individuals without PCD, those with PCD showed a significantly smaller volume of mastoid air cells and a significantly higher frequency of opacification of mastoid air cells and tympanic cavity on temporal bone CT. Otitis media raises suspicion for PCD, and the otological manifestations of PCD reported here could help to narrow the differential diagnosis and facilitate early treatment.

Fertility care among people with primary ciliary dyskinesia.

INTRODUCTION: Fertility care is important for people living with primary ciliary dyskinesia (PCD) who are at increased risk of fertility problems. We investigated fertility care in an international participatory study. METHODS: Participants of the COVID-PCD study completed an online questionnaire addressing fertility issues. We used logistic regression to study factors associated with fertility specialist visits. RESULTS: Among 384 respondents (response rate 53%), 266 were adults (median age 44 years, interquartile range [IQR]: 33-54, 68% female), 16 adolescents, and 102 parents of children with PCD. Only half of adult participants (128; 48%) received care from fertility specialists at a median age of 30 years (IQR: 27-33)-a median of 10 years after PCD diagnosis. Only 12% were referred to fertility specialists by their PCD physician. Fertility specialist visits were reported more often by adults with pregnancy attempts (odds ratio [OR]: 9.1, 95% confidence interval [CI]: 3.8-23.6) and among people who reported fertility as important for them (OR: 5.9, 95% CI: 2.6-14.6) and less often by females (OR: 0.4, 95% CI: 0.2-0.8). Only 56% of participants who talked with healthcare professionals about fertility were satisfied with information they received. They expressed needs for more comprehensive fertility information and reported dissatisfaction with physician knowledge about PCD and fertility. CONCLUSION: People with PCD are inconsistently referred to fertility specialists. We recommend care from fertility specialists become standard in routine PCD care, and that PCD physicians provide initial fertility information either at diagnosis or no later than transition to adult care.

Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial.

BACKGROUND: Mucociliary clearance is dysfunctional in people with primary ciliary dyskinesia, resulting in the accumulation of dehydrated mucus in the airways that is difficult to clear. We undertook a study to assess the benefit on lung function of treatment with a nebulised epithelial sodium channel (ENaC) blocker, idrevloride, with or without hypertonic saline, in people with primary ciliary dyskinesia. METHODS: The CLEAN-PCD trial was a phase 2, randomised, double-blind, placebo-controlled crossover trial conducted at 32 tertiary adult and paediatric care centres and university hospitals in Canada, Denmark, Germany, Italy, the Netherlands, Poland, the UK, and the USA. People with a confirmed diagnosis of primary ciliary dyskinesia, aged 12 years or older, with a percentage of predicted FEV1 (ppFEV1) in the range of 40% to <90%, were randomly assigned in a 2:2:1:1 ratio (block size=6), stratified by ppFEV1 at screening, to one of four sequences: (1) idrevloride in hypertonic saline in treatment period 1 then hypertonic saline in treatment period 2; (2) hypertonic saline in treatment period 1 then idrevloride in hypertonic saline in treatment period 2; (3) idrevloride in treatment period 1 then placebo in treatment period 2; and (4) placebo in treatment period 1 then idrevloride in treatment period 2. The idrevloride dose was 85 µg and hypertonic saline was 4·2% NaCl. 3 mL of each study treatment was nebulised twice daily for 28 days in treatment periods 1 and 2; the two 28-day treatment periods were separated by a 28-day washout period. The primary endpoint was absolute change from baseline in ppFEV1 after 28 days. Safety assessments and reports of adverse events were made at clinic visits during each treatment period and by a follow-up telephone call 28 days after the last dose of study drug. Additionally, adverse events could be reported at a follow-up telephone call 3 days after the start of dosing and as they arose. Participants who received at least one dose of study drug were included in the safety analyses (safety set), and those who also had spirometry data were included in the efficacy analyses (full analysis set). The completed study is registered (EudraCT 2015-004917-26; ClinicalTrials.govNCT02871778). FINDINGS: Between Sep 14, 2016, and May 31, 2018, 216 patients were screened and 123 were randomly assigned to one of four crossover sequences. Across the two treatment periods, treatment with idrevloride in hypertonic saline was initiated in 80 patients and completed in 78 patients (all 78 had data available and were included in the analysis); hypertonic saline initiated in 81 patients and completed in 76 patients (75 had data available and were included in the analysis); idrevloride initiated in 37 patients and completed in 35 patients (34 had data available and were included in the analysis); and placebo initiated in 36 patients and completed in 34 patients (all 34 had data available and were included in the analysis). Greater absolute increases in ppFEV1 from baseline to 28 days of treatment were seen with idrevloride in hypertonic saline (least-squares mean absolute change from baseline 1·0 percentage points, 95% CI -0·4 to 2·4) than with hypertonic saline alone (least-squares mean absolute change from baseline of -0·5 percentage points, -2·0 to 0·9; difference 1·5 percentage points, 95% CI <0·1 to 3·0; p=0·044). There was no significant difference in ppFEV1 for the parallel comparison of idrevloride in hypertonic saline compared with placebo or the crossover comparison of idrevloride with placebo. Adverse events were similar across treatments (57 to 65% of patients). Cough occurred in a greater proportion of participants during treatments that contained idrevloride or hypertonic saline compared with placebo, and oropharyngeal pain occurred in a greater proportion of participants during idrevloride treatments than during treatment with hypertonic saline alone or placebo, whereas chest discomfort was more common during treatments that included hypertonic saline. INTERPRETATION: In this phase 2 crossover study, idrevloride in hypertonic saline was safe and associated with improved lung function over a 28-day period in people with primary ciliary dyskinesia compared with hypertonic saline alone. Larger, longer clinical studies are warranted to explore the potential benefits of idrevloride in combination with hypertonic saline in people with primary ciliary dyskinesia. FUNDING: Parion Sciences, under agreement with Vertex Pharmaceuticals.

First preimplantation genetic testing case of Meckel syndrome with a novel homozygous TXNDC15 variant in a non-consanguineous Chinese family.

BACKGROUND: Meckel-Gruber syndrome (MKS) is a perinatally lethal, genetically heterogeneous, autosomal recessive condition caused by defective primary cilium formation. So far, the association of TXNDC15-related MKS has been reported in only five independent families from diverse ethnic origins, including Saudi, Pakistani, Estonian, and Indian. Here, we report a fetus diagnosed with MKS at 12 weeks, exhibiting typical ultrasound findings. METHODS: Low-coverage whole-genome sequencing was used to identify chromosomal abnormalities. Trio-base whole exome sequencing (trio-WES) was performed to investigate the potential pathogenic variants associated with MKS. Preimplantation genetic testing for monogenic disorders (PGT-M) was applied to prevent the transmission of the pathogenic variant. RESULTS: A novel homozygous pathogenic variant in the TXNDC15 gene was identified through trio-WES. The application of PGT-M successfully prevented the transmission of the pathogenic variant and resulted in an ongoing pregnancy. CONCLUSION: This is the first report of a TXNDC15 variant in the Chinese population and the first PGT case of TXNDC15-related MKS worldwide. The successful application of PGT-M in this family provides a potential approach for other monogenic diseases. Our case expands the variant spectrum of TXNDC15 and contributes to the molecular diagnosis and genetic counseling for MKS. This case underscores the importance of appropriate genetic testing methods and accurate genetic counseling in the diagnosis of rare monogenic diseases.

The airway microbiota in siblings with primary ciliary dyskinesia: Related factors and correlation with clinical characteristics.

OBJECTIVES-AIM: We aimed to show the composition and structure of and explore affecting factors on airway microbiota in primary ciliary dyskinesia (PCD) patients using culture-independent techniques. METHOD: A cross-sectional observational study was performed. We recruited 14 PCD patients (seven pairs of siblings) and nine parents. Bacterial rDNA was extracted from sputum and nasal samples. Sputum samples were also inoculated on suitable bacteriological media. RESULTS: Thirty-three separate genera were detected in sputum samples of PCD patients, and 41 were in nasal samples of parents. The detected genera were dominated by phyla Proteobacteria in PCD patients and their parents. Culture-dependent analyses could not detect many of the bacterial species detected with culture-independent analyses. There were no significant differences in alpha diversity between the siblings' pairs, and siblings' samples did not cluster together nearly as strongly as nonsiblings' samples. Patients who had no new complaints and no bacterial growth with the culture-dependent method at the time of study and patients who had no Haemophilus influenzae growth in the previous year had a significantly greater diversity (p < .05). Microbiota communities tended to cluster together by age, pulmonary exacerbation status, the existence of at least one H. influenzae growth with culture-dependent analyses in the previous year, and forced expiratory volume in 1 sec z and FEF25-75 z-scores. CONCLUSION: The airway microbiota of patients with PCD have presented more diverse bacterial communities than had been indicated with culture-dependent methods. The study identifies relationships between bacterial airway microbiota composition and the clinical measures of patients. Sibling pairs have no more community similarities than nonsibling PCD patients. Our results may indicate that the patients' clinical characteristics, which determine the disease severity, might affect the PCD microbiome.

Pulmonary functions, nasal symptoms, and quality of life in patients with primary ciliary dyskinesia (PCD).

BACKGROUND: Several factors may influence quality of life (QOL) for patients with primary ciliary dyskinesia (PCD). We aimed to evaluate the association between pulmonary functions, nasal symptoms and QOL in PCD patients. METHODS: A prospective single center study. Patients performed spirometry, whole body plethysmography, forced oscillation technique (FOT), lung clearance index (LCI), 6-min walk test (6MWT), and filled two questionnaires: a specific PCD QOL questionnaire (PCD-QOL) and Sino-nasal outcome test (SNOT-22) questionnaire, assessing symptoms of chronic rhinosinusitis and health related QOL. RESULTS: Twenty-seven patients (56% females), age 19.4 ± 10.5 years were included; their, FEV1 was 74.6 ± 22.7%, and RV/TLC was (157.3 ± 39.3% predicted). Health perception and lower respiratory symptoms domains of PCD-QOL had the lowest score (median [IQR]: 50 [33.3-64.6] and 57.1 [38.9-72.2], respectively). FOT parameters correlated with several PCD-QOL domains. R5 z-score (indicating total airway resistance) and AX z-score (indicating airway reactance) correlated negatively with physical domain (r = -0.598, p = .001, and r = -0.42, p = .03, respectively); R5 z-score also correlated negatively with hearing domain (r = -0.57, p = .002). R5-20 z-score (indicating small airway resistance) correlated negatively with role domain (r = -0.49, p = .03). SNOT-22 score correlated negatively with several PCD-QOL domains (lower respiratory symptoms r = -0.77, p < .001; physical r = -0.72, p < .001; upper respiratory symptoms r = -0.66, p < .001). No correlations were found between spirometry values, LCI, 6MWT, and PCD-QOL. CONCLUSIONS: FOT suggested small airway dysfunction, and correlated negatively with several PCD-QOL domains. Nasal symptoms had strong negative correlations with PCD-QOL. Larger longitudinal studies will further elucidate factors affecting QOL in PCD.