Cases Of Primary Ciliary Dyskinesia Research Articles

Combined approaches, including long-read sequencing, address the diagnostic challenge of HYDIN in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD), a disorder of the motile cilia, is now recognised as an underdiagnosed cause of bronchiectasis. Accurate PCD diagnosis comprises clinical assessment, analysis of cilia and the identification of biallelic variants in one of 50 known PCD-related genes, including HYDIN. HYDIN-related PCD is underdiagnosed due to the presence of a pseudogene, HYDIN2, with 98% sequence homology to HYDIN. This presents a significant challenge for Short-Read Next Generation Sequencing (SR-NGS) and analysis, and many diagnostic PCD gene panels do not include HYDIN. We have used a combined approach of SR-NGS with bioinformatic masking of HYDIN2, and state-of-the-art long-read Nanopore sequencing (LR_NGS), together with analysis of respiratory cilia including transmission electron microscopy and immunofluorescence to address the underdiagnosis of HYDIN as a cause of PCD. Bioinformatic masking of HYDIN2 after SR-NGS facilitated the detection of biallelic HYDIN variants in 15 of 437 families, but compromised the detection of copy number variants. Supplementing testing with LR-NGS detected HYDIN deletions in 2 families, where SR-NGS had detected a single heterozygous HYDIN variant. LR-NGS was also able to confirm true homozygosity in 2 families when parental testing was not possible. Utilising a combined genomic diagnostic approach, biallelic HYDIN variants were detected in 17 families from 242 genetically confirmed PCD cases, comprising 7% of our PCD cohort. This represents the largest reported HYDIN cohort to date and highlights previous underdiagnosis of HYDIN-associated PCD. Moreover this provides further evidence for the utility of LR-NGS in diagnostic testing, particularly for regions of high genomic complexity.

Diagnosis of Primary Ciliary Dyskinesia via Whole Exome Sequencing and Histologic Findings.

To assess the diagnostic potential of whole-exome sequencing (WES) and elucidate the clinical and genetic characteristics of primary ciliary dyskinesia (PCD) in the Korean population. Forty-seven patients clinically suspected of having PCD were enrolled at a tertiary medical center. WES was performed in all patients, and seven patients received biopsy of cilia and transmission electron microscopy (TEM). Overall, PCD was diagnosed in 10 (21.3%) patients: eight by WES (8/47, 17%), four by TEM. Among patients diagnosed as PCD based on TEM results, two patients showed consistent results with WES and TEM of PCD (2/4, 50%). In addition, five patients, who were not included in the final PCD diagnosis group, had variants of unknown significance in PCD-related genes (5/47, 10.6%). The most frequent pathogenic (P)/likely pathogenic (LP) variants were detected in DNAH11 (n=4, 21.1%), DRC1 (n=4, 21.1%), and DNAH5 (n=4, 21.1%). Among the detected 17 P/LP variants in PCD-related genes in this study, 8 (47.1%) were identified as novel variants. Regarding the genotype-phenotype correlation in this study, the authors experienced severe PCD cases caused by the LP/P variants in MCIDAS, DRC1, and CCDC39. Through this study, we were able to confirm the value of WES as one of the diagnostic tools for PCD, which increases with TEM, rather than single gene tests. These results will prove useful to hospitals with limited access to PCD diagnostic testing but with relatively efficient in-house or outsourced access to genetic testing at a pre-symptomatic or early disease stage.

Mutations in CFAP47, a previously reported MMAF causative gene, also contribute to the respiratory defects in patients with PCD.

Primary ciliary dyskinesia (PCD) is a genetic ciliopathy characterized by dysfunction of motile cilia. Currently, approximately 50 causative genes accounting for 60%-70% of all PCD cases have been identified in PCD-affected individuals, but the etiology in approximately 30%-40% of PCD cases remains unknown. We analyzed the clinical and genetic data of two PCD individuals who were suspected of having PCD. Whole-exome sequencing and Sanger sequencing were performed to identify and verify the variants in CFAP47. We also evaluated the expression of CFAP47 by real-time quantitative PCR and immunofluorescence. Transmission electron microscopy in respiratory epithelial cells was also conducted to analyze ciliary function. Two hemizygous missense variants of X-linked CFAP47 in two unrelated PCD individuals were identified. The expression of CFAP47 in two PCD individuals was significantly reduced in vivo and in vitro assays. A reduction in the amount of epithelial ciliary cells and basal bodies from PCD individuals was also observed. We describe two hemizygous missense variants of X-linked CFAP47 in two unrelated PCD individuals and prove CFAP47 variants are related to a reduced number of epithelial ciliary cells. Therefore, we suggest that CFAP47 should be known as a novel pathogenic gene of human PCD.

Ultrastructure for the diagnosis of primary ciliary dyskinesia in South Africa, a resource-limited setting.

International guidelines recommend a multi-faceted approach for successful diagnoses of primary ciliary dyskinesia (PCD). In the absence of a gold standard test, a combination of genetic testing/microscopic analysis of structure and function/nasal nitric oxide measurement is used. In resource-limited settings, often none of the above tests are available, and in South Africa, only transmission electron microscopy (TEM) is available in central anatomical pathology departments. The aim of this study was to describe the clinical and ultrastructural findings of suspected PCD cases managed by pediatric pulmonologists at a tertiary-level state funded hospital in Johannesburg. Nasal brushings were taken from 14 children with chronic respiratory symptoms in keeping with a PCD phenotype. Ultrastructural analysis in accordance with the international consensus guidelines for TEM-PCD diagnostic reporting was undertaken. TEM observations confirmed 43% (6) of the clinically-suspected cases (hallmark ultrastructural defects in the dynein arms of the outer doublets), whilst 57% (8) required another PCD testing modality to support ultrastructural observations. Of these, 25% (2) had neither ultrastructural defects nor did they present with bronchiectasis. Of the remaining cases, 83% (5) had very few ciliated cells (all of which were sparsely ciliated), together with goblet cell hyperplasia. There was the apparent absence of ciliary rootlets in 17% (1) case. In resource-limited settings in which TEM is the only available testing modality, confirmatory and probable diagnoses of PCD can be made to facilitate early initiation of treatment of children with chronic respiratory symptoms.

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice.

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

Deletions in DNAL1 Cause Primary Ciliary Dyskinesia Across North American Indigenous Populations

We report 4 cases of primary ciliary dyskinesia in unrelated indigenous North American children caused by identical, homozygous, likely pathogenic deletions in the DNAL1 gene. These shared DNAL1 deletions among dispersed indigenous populations suggest that primary ciliary dyskinesia accounts for more lung disease with bronchiectasis than previously recognized in indigenous North Americans.

Pediatric unilobar resection in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) causes chronic infections and progressive bronchiectasis that can lead to severe lung disease. Because there are no cures or regenerative therapy options for PCD, treatment of severe lung disease in PCD is focused on managing symptoms, including aggressive administration of antibiotics and diligent airway clearance. The Genetic Disorders of Mucociliary Clearance Consortium (GDMCC) does not recommend routine lobectomy, reserving its use for "rare cases of PCD with severe, localized bronchiectasis" and warns that a lobectomy should be treated with caution. However, if aggressive medical management fails, selective surgical removal of severely defective lung may result in maintenance or improvement of pulmonary function. Certainly, the decision to recommend lung resection in the face of chronic bronchiectasis from PCD requires an extensive discussion before it is considered as an alternative treatment. The purpose of this manuscript was to demonstrate that in selected cases of unilobar disease with bronchiectasis that are not responsive to other therapies (antibiotics and airway clearance), removal of localized necrotic areas of the lung along with prophylactic antibiotics can improve the quality of life of children with PCD associated bronchiectasis and improve growth and nutritional status, and pulmonary function.

Novel compound heterozygous CCDC40 mutations in a familial case of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by motile ciliary dysfunction and impaired ultrastructure. Despite numerous studies, the genetic basis for about 30% of PCD cases remains to be elucidated. Here, we present the identification and functional analysis of two novel mutations in the gene encoding coiled-coil domain-containing protein 40 (CCDC40), which are found in a familial case of PCD. These novel CCDC40 mutations, NM_017950.4: c.2236-2delA and c.2042_2046delTCACA, NP_060420.2: p.(Ile681fs), were identified by whole-exome sequencing (WES). Sanger sequencing was then performed to confirm the WES results and determine the CCDC40 gene sequences of the proband’s parents. The c.2042_2046delTCACA mutation disrupts the reading frame of the protein and is therefore predicted to produce a non-functional protein. Using a minigene assay with the pcDNA3.1(+) plasmid, we further investigated the potential pathogenic effects of the c.2236-2delA mutation and found that this mutation leads to formation of a truncated protein via splicing disruption. Thus, in summary, we identified two mutations of the CCDC40 gene that can be considered pathogenic compound heterozygous mutations in a case of familial PCD, thereby expanding the known mutational spectrum of the CCDC40 gene in this disease.

Inhaled delivery of a lipid nanoparticle encapsulated messenger RNA encoding a ciliary protein for the treatment of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a respiratory disease caused by dysfunction of the cilia with currently no approved treatments. This predominantly autosomal recessive disease is caused by mutations in any one of over 50 genes involved in cilia function; DNAI1 is one of the more frequently mutated genes, accounting for approximately 5–10% of diagnosed PCD cases. A codon-optimized mRNA encoding DNAI1 and encapsulated in a lipid nanoparticle (LNP) was administered to mice via aerosolized inhalation resulting in the expression human DNAI1 in the multiciliated cells of the pseudostratified columnar epithelia. The spatial localization of DNAI1 expression in the bronchioles indicate that delivery of the DNAI1 mRNA transpires the lower airways. In a PCD disease model, exposure to the LNP-encapsulated DNAI1 mRNA resulted in increased ciliary beat frequency using high speed videomicroscopy showing the potential for an mRNA therapeutic to correct cilia function in patients with PCD due to DNAI1 mutations.

A Novel Compound Heterozygous Mutation in the DNAH11 Gene Found in Neonatal Twins With Primary Ciliary Dyskinesis.

Background: Primary ciliary dyskinesia (PCD) is a rare genetically heterogeneous disorder of motile cilia. Common features of PCD include upper and lower respiratory tract disease, secretory otitis media, situs inversus and fertility problems. To date, although several PCD-associated genes have been identified, the genetic causes of most PCD cases remain elusive. Methods: In this case study, we analyzed the clinical and genetic data of one case of monochorionic diamniotic twins which were suspected of having PCD on the basis of clinical and radiological features including situs inversus, recurrent wet cough and sinusitis as well as varying degrees of respiratory distress. Whole-exome sequencing was performed to identify variants of the DNAH11 gene in the twins. Sanger sequencing and real-time quantitative polymerase chain reaction (RT-qPCR) were used for validation of DNAH11 variants both in the patient and the twins. Results: In the twins, we found a novel mutation at c.2436C > G (p.Y812 *) and a pathogenic deletion encompassing 2.0 Kb of 7P15.3 ([GRCh38] chr7: g.21,816,397-21,818,402). The deleted region included exons 64 and 65 of DNAH11. Sanger sequencing also revealed that the twins’ father was a carrier of heterozygous C.2436C > G and a heterozygous deletion was detected in the mother. No other clinically relevant genetic variants were identified. Conclusion: We describe a novel DNAH11 gene compound heterozygous mutation in newborn twins with PCD and recommend that PCD diagnosis should be considered in newborns presenting with respiratory distress and/or situs inversus. Early diagnosis and treatment of PCD will help control disease progression and improve the patient’s quality of life.

Ciliary Videomicroscopy: A Long Beat from the European Respiratory Society Guidelines to the Recognition as a Confirmatory Test for Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare inherited ciliopathy in which respiratory cilia are stationary or dyskinetic. The clinical presentation of PCD is highly non-specific since it includes infections and disorders of the upper (otitis and rhinosinusitis) and lower (neonatal respiratory distress, bronchitis, pneumonia and bronchiectasis) airways, starting in early life. Clinical examination alone does not allow a PCD diagnosis, which relies on several concordant tests, since none are sensitive or specific enough alone. Despite being the most sensitive and specific test to diagnose PCD, digital high-speed videomicroscopy (DHSV) is not sufficiently standardized, preventing its use with complete confidence as a confirmatory diagnostic test for PCD, or its inclusion in a diagnostic algorithm. Since the 2017 ERS recommendations for PCD diagnosis, three main issues remain to be solved in order to optimize DHSV ciliary beating evaluation: the problem in defining an accurate sensitivity and specificity as there is no gold standard method to diagnose all PCD cases, a lack of standardization in the operating procedure for processing respiratory samples, and in the choice of measured parameters (self-operating or not). The development of new automated analysis approaches is promising and will require full clinical validation.

A Comprehensive Approach for the Diagnosis of Primary Ciliary Dyskinesia-Experiences from the First 100 Patients of the PCD-UNIBE Diagnostic Center.

Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by dyskinetic cilia. Respiratory symptoms usually start at birth. The lack of diagnostic gold standard tests is challenging, as PCD diagnostics requires different methods with high expertise. We founded PCD-UNIBE as the first comprehensive PCD diagnostic center in Switzerland. Our diagnostic approach includes nasal brushing and cell culture with analysis of ciliary motility via high-speed-videomicroscopy (HSVM) and immunofluorescence labeling (IF) of structural proteins. Selected patients undergo electron microscopy (TEM) of ciliary ultrastructure and genetics. We report here on the first 100 patients assessed by PCD-UNIBE. All patients received HSVM fresh, IF, and cell culture (success rate of 90%). We repeated the HSVM with cell cultures and conducted TEM in 30 patients and genetics in 31 patients. Results from cell cultures were much clearer compared to fresh samples. For 80 patients, we found no evidence of PCD, 17 were diagnosed with PCD, two remained inconclusive, and one case is ongoing. HSVM was diagnostic in 12, IF in 14, TEM in five and genetics in 11 cases. None of the methods was able to diagnose all 17 PCD cases, highlighting that a comprehensive approach is essential for an accurate diagnosis of PCD.

Clinical and molecular characteristics of primary ciliary dyskinesia: A tertiary care centre experience.

BackgroundPrimary ciliary dyskinesia (PCD) is a ciliopathy with diverse clinical and genetic findings caused by abnormal motile cilia structure and function. In this study, we describe the clinical characteristics of confirmed PCD cases in our population and report the radiological, genetic, and laboratory findings.MethodsThis was a retrospective, observational, single-centre study. We enrolled 18 patients who were diagnosed with confirmed PCD between 2015 and 2019. We then analyzed their data, including clinical findings and workup.ResultsIn our cohort, 56% of patients had molecularly confirmed PCD, and RSPH9 was the most common gene identified. Transmission electron microscopy (TEM) showed an ultrastructural defect in 64% of samples, all of which matched the genetic background of the patient. Situs inversus (SI) was observed in 50% of patients, and congenital heart disease was observed in 33%. The median body mass index (BMI) was 15.87 kg/m2, with a median z score of -1.48. The median FEV1 value was 67.6% (z score - 2.43). Radiologically, bronchiectasis was noted in 81% of patients at a variable degree of severity. Lung bases were involved in 91% of patients. We were unable to correlate the genotype-phenotype findings.ConclusionWe describe the clinical and molecular characteristics of patients with confirmed PCD in a tertiary centre in Saudi Arabia and report 9 new pathogenic or likely pathogenic variants in one of the PCD-associated genes.

Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China

Primary ciliary dyskinesia (PCD) is a heterogeneous disease with a diverse clinical and genetic spectrum among populations worldwide. Few cases of pediatric PCD have been reported from China. What are the clinical and genotypic characteristics of children with PCD in China? Clinical characteristics, laboratory findings, and genetic results obtained for 75 patients with PCD were reviewed retrospectively at a single center in China. Genetic sequencing was conducted using whole-exome screening. Patient median age at diagnosis was 7.0 years (range, 2 months-14 years). Of 75 patients, 88%(66/75) had chronic wet cough, 77%(58/75) had recurrent sinusitis, 76%(57/75) had bronchiectasis, 40%(30/75) had neonatal respiratory distress, and 28%(21/75) had coexistent asthma. Notably, postinfectious bronchiolitis obliterans (PIBO) as first presentation was found in 8%of children (6/75). Genes with the highest incidence of mutations were DNAH11 (15/51), followed by DNAH5 (9/51), CCDC39 (5/51), DNAH1 (4/51), and CCNO (3/51). Four genes (DNAI1, HEATR2, RSPH9, and DNAAF3) each were respectively found in two patients, and seven genes (CCDC40, LRRC6, SPAG1, RSPH4A, ARMC4, CCDC114, and DNAH14, a novel gene) each were mutated once. No differences in classical clinical features were observed among patients with commonly observed PCD-associated genotypes. However, three of six PIBO patients carried DNAH1 mutations. Besides typical clinical features, PIBO was observed as the first presentation of pediatric PCD in China. An association of the novel gene DNAH14 with PCD was observed, expanding the PCD genotypic spectrum.

Implementation of a screening tool for primary ciliary dyskinesia (PCD) in a pediatric otolaryngology clinic

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disease arising from motile ciliary dysfunction and associated with recurrent and chronic upper and lower respiratory tract infections. Pediatric otolaryngologists may see these patients prior to the development of lung disease. Features of PCD may overlap with other suppurative respiratory diseases, creating diagnostic challenges. A simple screening tool would be beneficial to identify potential patients who have chronic upper respiratory tract disease requiring further specialist evaluation. ObjectiveTo test a simple screening tool consisting of four questions to detect PCD in children with chronic otitis media and chronic rhinosinusitis seen in a tertiary otolaryngology clinic. MethodsA prospective, single site, observational study in a tertiary care pediatric otolaryngology clinic. Children aged 3–17 years diagnosed with chronic otitis media or rhinosinusitis with onset at less than 2 years of age were recruited. All study subjects had at least one of four key clinical features for PCD as determined by answers to screening questions, while control subjects had none. All participants completed a medical history questionnaire and nasal nitric oxide measurements. Those with reduced nasal nitric oxide levels were referred to our PCD center for further evaluation. ResultsA total of 153 patients were screened and 62 subjects were enrolled. Of those, 35 were enrolled as study subjects and 27 as matched controls. Study subjects had mean age of 7.5 years (3.2–16.5) with pre-screening diagnosis of chronic otitis media (n = 29) or chronic rhinosinusitis (n = 6). Control subjects (n = 27) had mean age 7.2 years (3.0–16.3) with pre-screening diagnosis of chronic otitis media (n = 25), and chronic rhinosinusitis (n = 2). There were no differences in subject demographics or mean nasal nitric oxide values between the two groups (179.8 vs 210.8 nl/min). Ten individuals had low nasal nitric oxide values, 7 of which were normal on repeat testing. Three subjects failed to return for follow up evaluations. Four referrals were made for further evaluation on the basis of clinical symptoms and nasal nitric oxide results. While no new cases of PCD were detected, a subject and his sibling with recurrent sinopulmonary infections were referred for immunologic evaluation. ConclusionThe use of standardized screening questions can be used in an otolaryngology clinic to identify patients who require further evaluation for PCD or primary immunodeficiency.

Pediatric unilobar resection in primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) causes chronic infections and progressive bronchiectasis that can lead to severe lung disease. Because there are no cures or regenerative therapy options for PCD, treatment of severe lung disease in PCD is focused on managing symptoms, including aggressive administration of antibiotics and diligent airway clearance. The Genetic Disorders of Mucociliary Clearance Consortium (GDMCC) does not recommend routine lobectomy, reserving its use for "rare cases of PCD with severe, localized bronchiectasis" and warns that a lobectomy should be treated with caution. However, if aggressive medical management fails, selective surgical removal of severely defective lung may result in maintenance or improvement of pulmonary function. Certainly, the decision to recommend lung resection in the face of chronic bronchiectasis from PCD requires an extensive discussion before it is considered as an alternative treatment. The purpose of this manuscript was to demonstrate that in selected cases of unilobar disease with bronchiectasis that are not responsive to other therapies (antibiotics and airway clearance), removal of localized necrotic areas of the lung along with prophylactic antibiotics can improve the quality of life of children with PCD associated bronchiectasis and improve growth and nutritional status, and pulmonary function.

NME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a hereditary defect of motile cilia in humans and several domestic animal species. Typical clinical findings are chronic recurrent infections of the respiratory tract and fertility problems. We analyzed an Alaskan Malamute family, in which two out of six puppies were affected by PCD. The parents were unaffected suggesting autosomal recessive inheritance. Linkage and homozygosity mapping defined critical intervals comprising ~118 Mb. Whole genome sequencing of one case and comparison to 601 control genomes identified a disease associated frameshift variant, c.43delA, in the NME5 gene encoding a sparsely characterized protein associated with ciliary function. Nme5-/- knockout mice exhibit doming of the skull, hydrocephalus and sperm flagellar defects. The genotypes at NME5:c.43delA showed the expected co-segregation with the phenotype in the Alaskan Malamute family. An additional unrelated Alaskan Malamute with PCD and hydrocephalus that became available later in the study was also homozygous mutant at the NME5:c.43delA variant. The mutant allele was not present in more than 1000 control dogs from different breeds. Immunohistochemistry demonstrated absence of the NME5 protein from nasal epithelia of an affected dog. We therefore propose NME5:c.43delA as the most likely candidate causative variant for PCD in Alaskan Malamutes. These findings enable genetic testing to avoid the unintentional breeding of affected dogs in the future. Furthermore, the results of this study identify NME5 as a novel candidate gene for unsolved human PCD and/or hydrocephalus cases.

Infant nasal nitric oxide over time: natural evolution and impact of respiratory tract infection.

Nasal nitric oxide (NO) discriminates between patients with primary ciliary dyskinesia (PCD) and healthy individuals. We report feasibility of measurement and natural evolution of nasal NO and upon the impact of respiratory tract infection (RTI) on nasal NO in healthy infants (HI), followed from birth until age 2 years, with comparison to nasal NO in infant PCD.Tidal-breathing nasal NO measurements were performed at scheduled visits at 2 weeks old and at 4, 8, 12, 18 and 24 months old, with extra visits during RTIs. Historical nasal NO measurements for infant PCD were included for comparison.Altogether, 224 nasal NO measurements were performed in 44 enrolled infants. Median newborn nasal NO was 46 ppb (interquartile range (IQR) 29-69 ppb), increasing at a rate of 5.4% per month up to 283 ppb (IQR 203-389 ppb) at the age of 2 years. RTIs in 27 out of 44 infants temporarily suppressed nasal NO by 79%. Values for nasal NO in seven infants with PCD ranged from 6-80 ppb. The success rate to accept nasal NO sampling was 223 out of 224 measurements (99.6%).Tidal-breathing nasal NO measurement was indeed feasible in infancy and nasal NO in HI increased significantly up to 2 years of age, in opposition to nasal NO in PCD cases, which stayed low past 2 years of age. RTI episodes caused marked, temporary reductions in nasal NO in HI indistinguishable from that in infant PCD, suggesting that nasal NO should be measured in RTI-free intervals.

The clinical characteristics of 17 cases of primary ciliary dyskinesia

Objective: To review the clinical data of cases of primary ciliary dyskinesia (PCD), and to explore the clinical characteristics for the understanding of PCD. Methods: We retrospectively summarized 17 patients with PCD diagnosed in Peking Union Medical College Hospital from Jan 2009 to Dec 2014. There were 7 male and 10 female patients, with the age from 6 to 57 years at the time of diagnosis. The mean onset age of the disease was 11.7±2.1 years, and the mean age at diagnosis was 29.5±3.5 years. We analyzed their clinical symtoms, radiologic images, pulmonary function test and the electron microscopic findings for the clinical characteristics of PCD. Results: The most common onset symptoms were cough (15/17) or sputum (13/17) among our 17 patients with PCD. Only 5 patients had situs inversus in our group. Sixteen patients had bronchiectasis on chest CT scan. Nasal sinusitis was confirmed by nasal CT scan in 15 patients. The most common pathogens from sputum cultures included Pseudomonas aeruginosa, Haemophilus influenzea, Aspergillus fumigates and Candida (3/14 respectively). None of the patients had evidence of mycobacterial infection. Twelve patients underwent spirometry and obstructive pattern was the most common disorder (8/12). Diffusion impairment (5/10) and restrictive pattern dysfunction (3/10) were also present in our patients. Two patients had normal pulmonary function test results. Thirteen patients underwent bronchial mucosal ciliary electron microscopy and the most abnormalities were outer or inner dynein arms deficiency (8/13), and other abnormalities included microtubule arrangement disorder (3/13), reduction of the number of microtubules (3/13) and reduction of the number of dynein arms (2/13). Four of our patients had multiple dysfunctions on their ciliaries. Conclusions: PCD should be considered in bronchiectasis patients with disease onset at childhood even without situs inverse, especially those accompanied with nasal sinusitis or otitis media. Chest or paranasal sinus CT scan, and male sperm examination were helpful for the diagnosis. Mucosal ciliary electron microscopy was an efficient diagnostic method for PCD.

Comparison of Bronchoalveolar Lavage and Sputum Microbiology in Patients with Primary Ciliary Dyskinesia

Chronic infections of primary ciliary dyskinesia (PCD) airways are strongly associated with morbidity and mortality; however, relatively limited data exist about their microbiology. Therefore, this study was aimed to determine whether there was a correlation between sputum and bronchoalveolar lavage (BAL) microbiology in PCD cases. This was accomplished by comparing the lower airway bacteriology in PCD with the results of sputum samples. We retrospectively analyzed the microbiology of BAL and sputum samples of 114 patients who were diagnosed as PCD and followed up at Hacettepe University Hospital Department of Pediatric Pulmonology. At the time of sampling, patients had no pulmonary exacerbation, and sputum samples were obtained within 3 months of BAL. The mean age of the patients was 13.5 ± 4.3 (range 3–21 years) years. Microbiological analysis revealed microorganisms in 47.4% of sputum samples and in 63.2% of BAL samples. In both BAL and sputum samples, Haemophilus influenzae was the most frequent patho...