Prevalence Of Primary Ciliary Dyskinesia Research Articles

Primary ciliary dyskinesia: Meeting the challenges of diagnosis in South Africa.

Primary ciliary dyskinesia (PCD) is an inherited ciliopathy that results in impaired mucous clearance and affects primarily the respiratory tract, causing upper airway disease, bronchial inflammation and bronchiectasis. The prevalence of PCD in low- and middle-income settings, including South Africa (SA), is unknown, largely owing to challenges with diagnosis, and identifying children or adults with PCD is challenging in a setting with a high prevalence of other infectious diseases, including lower respiratory tract infections and tuberculosis. No single test is diagnostic of PCD, and while some tests are costly, others are labour intensive and require highly specialised laboratory expertise. In the SA setting, awareness and opportunities for the diagnosis of PCD need to be created. In this commentary, we provide a pragmatic approach to identifying which children and adults require further investigations for PCD using a range of diagnostic tests or tools that are available. Furthermore, we recommend that designated centres of expertise for PCD diagnosis are created in SA. This would be an important step towards improving accessibility of diagnostic tests and developing local expertise to improving PCD diagnosis, especially in early childhood, to prevent long-term irreversible respiratory sequelae.

Classification of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare hereditary disease from the group of ciliopathies with extensive locus and allelic heterogeneity (ORPHA 244, 98861; OMIM 242650, 244000). This disease is inherited by autosomal dominant or autosomal recessive type and, less often, by X-linked type (OMIM 300424). Retinitis pigmentosa develops in the X-linked PCD variant. The overall minimum global prevalence of PCD according to European data is 1 : 7554. There is no generally accepted classification of PCD in the international classification of diseases (ICD), 10th revision. PCD is not presented in ICD-10 as a separate medical entity, and the code Q32.4 – Other congenital bronchial anomalies – is used for coding. In the new edition of ICD-11, the code LA75.Y is highlighted – Other specified structural abnormalities of the lungs.Primary ciliary dyskinesia. However, there is no generally accepted classification of PCD. The aim of the study was to develop a classification of primary ciliary dyskinesias to improve the efficiency of medical care for patients during follow-up.Methods. European and Russian clinical recommendations, as well as ICD 10th and 11th revision, Classification of Respiratory Insufficiency (2020), Order of 27.08.19 No.585n “On classifications and criteria used in the implementation of medical and social expert assessment of citizens by federal state institutions of medical and social expert assessment” (as amended on 06.10.21) were used to create the classification.Results. The classification of PCD was created and can be recommended for use in clinical practice. The classification was based on the presence or absence of the Sievert – Kartagener syndrome (complete, not complete), as well as clinical and instrumental characterization of bronchopulmonary changes based on the presence of chronic obstructive bronchitis, bronchiectasis (specifying the type and localization), pneumofibrosis with the process activity (exacerbation, remission), and the degree of respiratory failure. It is recommended to take into account extrapulmonary manifestations of PCD, such as rhinosinusitis, media otitis, congenital heart defect, and complications. It is recommended to use the PICADAR (PrImary CiliAry DyskinesiA Rule) score and to include the results of video microscopy, DNA diagnosis, and microbiological examination in the diagnosis.Conclusion. The application of the proposed classification can be useful in the dynamic observation of the patient, therapy and in the conduct of medical and social expert assessment.

Prevalence and founder effect of DRC1 exon 1-4 deletion in Korean patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder affecting ciliary structure and function. PCD exhibiting dynein regulatory complex subunit 1 (DRC1) exon 1-4 deletion has been reported in several Japanese PCD patients; however, no large scale studies have been performed. Here, we aimed to determine the prevalence and founder effect of this variant in the Korean population. Using an in-house copy number variation tool, we screened for DRC1 exon 1-4 deletion in 20 patients with PCD and exome data of 1435 patients in the Seoul National University Hospital repository. In cases of suspected DRC1 deletion, confirmatory gap-PCR was performed. In a PCD cohort, three of 20 (15%) patients were positive for DRC1 exon 1-4 deletion (NM_145038.5(DRC1): c.1-3952_540 + 1331del27748-bp) while pathogenic variants were found in CCDC39 (N = 1), DNAAF6 (N = 1), DNAH9 (N = 1). In the 1,435-sample exome data, seven patients (0.49%) were confirmed to have DRC1 exon 1-4 deletion. A chimeric sequence including the junction was searched from the 1000 Genomes Project data repository. One Japanese patient (0.96%) was found to have the same DRC1 exon 1-4 deletion, which was absent in other populations. This study demonstrated that the DRC1 exon 1-4 deletion is a founder mutation based on haplotype analysis. In summary, the prevalence of PCD based on DRC1 exon 1-4 deletion is particularly high in Korean and Japanese populations, which is attributed to the founder effect. Genetic testing for DRC1 exon 1-4 deletion should be considered as an initial screening tool for Korean and Japanese patients with PCD.

Abstract 14317: The Prevalence of Motile Ciliary Gene Variants in Children With Transposition of the Great Arteries and Tetralogy of Fallot

Introduction: Motile ciliary dysfunction plays a central role in the pathogenesis of respiratory abnormalities and congenital heart disease (CHD). The role of ciliary gene variants in the non-heterotaxic CHD population is not well characterised. Methods: This single-centre retrospective cohort study aimed to determine the prevalence of Primary Ciliary Dyskinesia (PCD) gene variants in children with isolated Transposition of the Great Arteries (TGA) and Tetralogy of Fallot (TOF). Patients with whole genome sequencing between 2008-2018 were included. We identified pathogenic (P) or likely pathogenic (LP) single-nucleotide variants (SNVs) and short insertion/deletions (indels) in coding regions of 45 genes known to cause PCD. Patient characteristics and associated respiratory outcomes were evaluated from chart reviews. Results: PCD gene variants were found in 2.9% (5/172) TGA and 3.8% (10/264) TOF patients. Thirteen probands were heterozygous for P/LP SNVs/ indels; CCDC40 N=6, DNAH11 N=2, SPAG1 N=2 and one each of DNAH8/DNAAF1/ARMC4. Two were compound heterozygotes for variants in DNAH11 and DNAH8. At last follow-up, mean age was 14.5 years (SD 6.8, 57.9% male) and 7 deaths had occurred. Asthma was diagnosed in 10.5% TGAs and 8.1% TOFs with 3.9% and 7.3% respectively requiring hospitalisation for primary respiratory illness. In the variant positive subgroup, 5/15 had respiratory abnormalities - bronchiectasis (N = 1), asthma (N = 2), neonatal cough (N = 1), ventilator-associated pneumonia (N = 2). Additional cardiac anomalies occurred in 53% (8/15) - abnormal systemic veins (N = 3), situs inversus, dextrocardia (N = 1), right arch (N = 5), hypoplastic right ventricle (N = 1). An abnormal coronary pattern was seen in 4/5 TGAs. Vaginal and renal agenesis each occurred in 1 patient. Conclusions: Our findings suggest a high prevalence and potential association of ciliary gene variants with respiratory outcomes and situs anomalies in non-heterotaxy CHD.

Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the island. The nNO level differentiated homozygous subjects with PCD due to the RSPH4A (c.921+3_921+6del (intronic)) founder mutation compared to healthy gender-age matched controls and subjects with VUS or negative genetic testing for PCD. The acquisition of state-of-the-art diagnostic tools such as nNO positively impacted and expanded our current PCD diagnostic capabilities in Puerto Rico for our founder genetic mutation. The addition of nNO technology promotes earlier disease screening and recognition for patients with PCD on the island. The access to nNO helped us to properly characterize the PCD diagnosis for patients with the RSPH4A (c.921+3_921+6del (intronic)). As a result, our findings will allow us to be part of the national PCD foundation registry and represent Puerto Rican Hispanics in future PCD multicentric clinical trials.

Clinical phenotypes of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and the incidence of congenital heart disease is also high. The pathogenesis behind PCD is that gene variants cause structural or functional disorders of respiratory cilia and motile cilia of other organs, leading to a series of heterogeneous clinical manifestations, which makes it difficult to identify and diagnose PCD. Combining different disease screening tools and understanding the relationship between genotypes and phenotypes may facilitate early diagnosis and treatment for PCD.

The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis

Primary ciliary dyskinesia (PCD) is a motile ciliopathy characterised by otosinopulmonary infections. Inheritance is commonly autosomal recessive, with extensive locus and allelic heterogeneity. The prevalence is uncertain. Most genetic studies have been done in North America or Europe. The aim of the study was to estimate the worldwide prevalence and ethnic heterogeneity of PCD. We calculated the allele frequency of disease-causing variants in 29 PCD genes associated with autosomal recessive inheritance in 182 681 unique individuals to estimate the global prevalence of PCD in seven ethnicities (African or African American, Latino, Ashkenazi Jewish, Finnish, non-Finnish European, east Asian, and south Asian). We began by aggregating variants that had been interpreted by Invitae, San Francisco, CA, USA, a genetics laboratory with PCD expertise. We then determined the allele frequency of each variant (pathogenic, likely pathogenic, or variant of uncertain significance [VUS]) in the Genome Aggregation Database (gnomAD), a publicly available next-generation sequencing database that aggregates exome and genome sequencing information from a wide variety of large-scale projects and stratifies allele counts by ethnicity. Using the Hardy-Weinberg equilibrium equation, we were able to calculate a lower-end prevalence of PCD for each ethnicity by including only pathogenic and likely pathogenic variants; and upper-end prevalence by also including VUS. This approach was similar to previous work on Li-Fraumeni (TP53 variants) prevalence. We were not diagnosing PCD, but rather estimating prevalence based on known variants. The overall minimum global prevalence of PCD is calculated to be at least one in 7554 individuals, although this is likely to be an underestimate because some variants currently classified as VUS might be disease-causing and some pathogenic variants might not be detected by our methods. In the overall cohort, Invitae data could be included for variants without gnomAD data for a primary ethnicity. When using only gnomAD allele frequencies to calculate prevalence in individual ethnicities, the estimated prevalence of PCD was lower in each ethnicity compared with the overall cohort. This is because the overall cohort includes additional data from the Invitae database such as copy number variants and other variants not present in gnomAD. With gnomAD we found the expected PCD frequency to be higher in individuals of African ancestry than in most other populations (excluding VUS: 1 in 9906 in African or African American vs 1 in 10 388 in non-Finnish European vs 1 in 14 606 in east Asian vs 1 in 16 309 in Latino; including VUS: 1 in 106 in African or African American vs 1 in 178 in non-Finnish European vs 1 in 196 in Latino vs 1 in 188 in east Asian). In addition, we found that the top 5 genes most commonly implicated in PCD differed across ethnic ancestries and contrasted commonly published findings. PCD appears to be more common than has been recognised, particularly in individuals of African ancestry. We identified gene distributions that differ from those in previous European and North American studies. These results could have an international impact on case identification. Our analytic approach can be expanded as more PCD loci are identified, and could be adapted to study the prevalence of other inherited diseases. None.

Investigation of Primary Ciliary Dyskinesia in Children with Bronchiectasis in Iran

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder with signs and symptoms of recurrent chronic sinusitis, otitis media, pneumonia, bronchiectasis, male infertility, and situs inversus. The diagnosis of PCD has always been one of the challenging issues that is mostly made through screening tests. These include the saccharin test and measurements of exhaled and nasal nitric oxide (NO) level, transmission electron microscopy (TEM) for evaluating ultrastructure of the cilia, high-speed video microscopy for evaluating ciliary beat patterns, immunofluorescent staining of the cilia in the biopsies, and genetic studies. As there had not been any epidemiological studies in Iran to detect the prevalence of PCD in the general population, the current research has been undertaken for the first time using screening tests of saccharin and measurement of the level of exhaled NO (fractional exhaled NO) to investigate the prevalence of PCD. Objectives: Primary ciliary dyskinesia (PCD) is a rare genetic disorder with the basis of an abnormal ciliary movement that causes chronic respiratory infections, bronchiectasis, infertility in males, and situs inversus. The significance of earlier diagnosis is for better care and prevention of complications. In this regard, we studied the PCD in children with bronchiectasis by saccharin test and measurement of exhaled nitric oxide. Methods: In this cross-sectional study, 31 patients with a definite diagnosis of bronchiectasis were evaluated regarding nitric oxide exhalatory measurement (FeNO) and a saccharin test for the confirmation of PCD diagnosis. The cut-off point of 20 ppb was considered as the normal level for FeNO test and the sensation of fewer than 60 minutes for the normal range of the saccharin test. Age, gender, and cardioposition were recorded for the patients. Results: Unlike the saccharine test, the measurement of exhaled nitric oxide had a high sensitivity (90.3% versus 54.8%) for the diagnosis of PCD. Cardioposition and gender did not have significant effects on the outcomes of exhaled NO and saccharin test (P-value > 0.05). Besides, the patients’ age did not affect FeNO measurement but was significantly higher among those with abnormal saccharin test (P-value = 0.028). Conclusions: The FeNO test had a remarkable sensitivity of 90.3% for the diagnosis of PCD, and its outcomes were not affected by age, gender, and cardioposition. The saccharin test had a sensitivity of 54.8% and was influenced by age, while not by gender or cardioposition. Although there are more accurate tests for diagnosis of PCD such as TEM and genetic studies, we decided to investigate PCD in children with bronchiectasis by performing two screening tests, NO and saccharin, because of several issues.

The prevalence of the defining features of primary ciliary dyskinesia within a cri du chat syndrome cohort.

Primary ciliary dyskinesia (PCD) and cri du chat syndrome (CdCS) are distinct disorders that can co-occur due to a common genetic locus on chromosome 5p. Chronic respiratory symptoms associated with PCD can occur in CdCS and are typically attributed to hypotonia, dysphagia, and aspiration. The prevalence of PCD among individuals with CdCS is not known. An online survey assessing common features of PCD was distributed to members of the 5P Minus Society, a cri du chat patient advocacy group. Respondents who met criteria for elevated risk of PCD (at least 3 symptoms or other features highly suggestive of PCD) were offered PCD genetic testing. For the 123 respondents (median age 10.1 years with IQR 5.5-17.3 years; from 33 U.S. states and 10 other countries) chronic respiratory symptoms associated with PCD were prevalent, including unexplained neonatal respiratory distress, year-round nasal congestion beginning in infancy, and year-round, wet cough beginning in infancy in 35%, 32%, and 20% of respondents, respectively. Fifteen respondents (12%) met criteria for elevated risk for PCD and completed genetic analysis; however, none were diagnostic for PCD. A PCD clinical center evaluated an additional subject with CdCS who met criteria for likely PCD and had negative genetics, but had diagnostic electron microscopy of the respiratory cilia (missing outer dynein arms). Clinicians should be aware of the genetic connection between CdCS and PCD. Non-informative genetic testing does not rule out PCD. CdCS patients with chronic respiratory symptoms may benefit from referral to specialized PCD diagnostic centers.

Primary ciliary dyskinesia: mechanisms and management.

Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia that is predominantly inherited in an autosomal-recessive fashion. It is associated with abnormal ciliary structure and/or function leading to chronic upper and lower respiratory tract infections, male infertility, and situs inversus. The estimated prevalence of primary ciliary dyskinesia is approximately one in 10,000–40,000 live births. Diagnosis depends on clinical presentation, nasal nitric oxide, high-speed video-microscopy analysis, transmission electron microscopy, genetic testing, and immunofluorescence. Here, we review its clinical features, diagnostic methods, molecular basis, and available therapies.

High prevalence of CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations

RationalePrimary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of...

Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies.

Primary ciliary dyskinesia (PCD) is an orphan disease (MIM 244400), autosomal recessive inherited, characterized by motile ciliary dysfunction. The estimated prevalence of PCD is 1:10,000 to 1:20,000 live-born children, but true prevalence could be even higher. PCD is characterized by chronic upper and lower respiratory tract disease, infertility/ectopic pregnancy, and situs anomalies, that occur in ≈50% of PCD patients (Kartagener syndrome), and these may be associated with congenital heart abnormalities. Most patients report a daily year-round wet cough or nose congestion starting in the first year of life. Daily wet cough, associated with recurrent infections exacerbations, results in the development of chronic suppurative lung disease, with localized-to-diffuse bronchiectasis. No diagnostic test is perfect for confirming PCD. Diagnosis can be challenging and relies on a combination of clinical data, nasal nitric oxide levels plus cilia ultrastructure and function analysis. Adjunctive tests include genetic analysis and repeated tests in ciliary culture specimens. There are currently 33 known genes associated with PCD and correlations between genotype and ultrastructural defects have been increasingly demonstrated. Comprehensive genetic testing may hopefully screen young infants before symptoms occur, thus improving survival. Recent surprising advances in PCD genetic designed a novel approach called “gene editing” to restore gene function and normalize ciliary motility, opening up new avenues for treating PCD. Currently, there are no data from randomized clinical trials to support any specific treatment, thus, management strategies are usually extrapolated from cystic fibrosis. The goal of treatment is to prevent exacerbations, slowing the progression of lung disease. The therapeutic mainstay includes airway clearance maneuvers mainly with nebulized hypertonic saline and chest physiotherapy, and prompt and aggressive administration of antibiotics. Standardized care at specialized centers using a multidisciplinary approach that imposes surveillance of lung function and of airway biofilm composition likely improves patients’ outcome. Pediatricians, neonatologists, pulmonologists, and ENT surgeons should maintain high awareness of PCD and refer patients to the specialized center before sustained irreversible lung damage develops. The recent creation of a network of PCD clinical centers, focusing on improving diagnosis and treatment, will hopefully help to improve care and knowledge of PCD patients.

Lung Disease in Primary Ciliary Dyskinesia

Clinical Image: This is a 56 year old male with history of Primary Ciliary Dyskinesia (PCD) presented with hypoxia and cough with mucopurulent sputum. Since past 34 years patient has been troubled by recurrent severe lung infections requiring multiple hospital admissions. PCD is characterized by obstructive pattern of lung disease. The images depict classic cystic bronchodilatation (Figure 1) with bronchiectasis predominantly affecting lower lung lobes (Figure 2). The mainstays of treatment are airway clearance and aggressive antibiotic therapy. PCD is a rare ciliopathic autosomal recessive genetic disorder that causes defects in action of cilia lining the respiratory tract, fallopian tubes, as well as the flagella of sperm cells. The prevalence of PCD is about 1:10,000. Severe lung infections by virulent bacteria are the main cause of morbidity and mortality in these patients. Lung transplant is the only curative treatment in these patients.

Prevalence of primary ciliary dyskinesia in consecutive referrals of suspect cases and the transmission electron microscopy detection rate: a systematic review and meta-analysis.

Diagnostic testing for primary ciliary dyskinesia (PCD) usually includes transmission electron microscopy (TEM), nasal nitric oxide, high-speed video microscopy, and genetics. Diagnostic performance of each test should be assessed toward the development of PCD diagnostic algorithms. We systematically reviewed the literature and quantified PCD prevalence among referrals and TEM detection rate in confirmed PCD patients. Major electronic databases were searched until December 2015 using appropriate terms. Included studies described cohorts of consecutive PCD referrals in which PCD was confirmed by at least TEM and one additional test, in order to compare the index test performance with other test(s). Meta-analyses of pooled PCD prevalence and TEM detection rate across studies were performed. PCD prevalence among referrals was 32% (95% CI: 25-39%, I2 = 92%). TEM detection rate among PCD patients was 83% (95% CI: 75-90%, I2 = 90%). Exclusion of studies reporting isolated inner dynein arm defects as PCD, reduced TEM detection rate and explained an important fraction of observed heterogeneity (74%, 95% CI: 66-83%, I2 = 66%). Approximately, one third of referrals, are diagnosed with PCD. Among PCD patients, a significant percentage, at least as high as 26%, is missed by TEM, a limitation that should be accounted toward the development of an efficacious PCD diagnostic algorithm.

Recent advances in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disease inherited in an autosomal recessive manner. The prevalence of PCD is estimated to be 1 in 20,000 live births. Congenital abnormality of the primary cilia results in situs inversus in 50% of patients. Decreased function of motile cilia causes chronic rhinosinusitis, otitis media with effusion, bronchiectasis and infertility. Cases with situs inversus are considered to show "Kartagener's syndrome", and diagnosis is not difficult. However, in cases without situs inversus, the diagnosis is much more troublesome. PCD without situs inversus is thus probably underdiagnosed. Prolonged chronic cough represents an important symptom that is seen in most patients. The diagnosis of PCD requires the presence of the characteristic clinical phenotypes and either: (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of respiratory epithelium; or (2) identification of mutation in one of the genes known to be associated with PCD. Nasal nitric oxide concentration is extremely low in PCD, and this could be useful for screening of the disease. At present, no fundamental therapies are available for PCD. Diagnosis in the early stages is important to prevent progression of bronchiectasis and deterioration of lung function by guidance for daily life, immunization, cessation of smoking and prompt therapy at the time of respiratory tract infection. Since PCD is inherited in an autosomal-recessive manner, genetic counseling is necessary after definite diagnosis.

The prevalence of clinical features associated with primary ciliary dyskinesia in a heterotaxy population: results of a web-based survey.

Primary ciliary dyskinesia and heterotaxy are rare but not mutually exclusive disorders, which result from cilia dysfunction. Heterotaxy occurs in at least 12.1% of primary ciliary dyskinesia patients, but the prevalence of primary ciliary dyskinesia within the heterotaxy population is unknown. We designed and distributed a web-based survey to members of an international heterotaxy organisation to determine the prevalence of respiratory features that are common in primary ciliary dyskinesia and that might suggest the possibility of primary ciliary dyskinesia. A total of 49 members (25%) responded, and 37% of the respondents have features suggesting the possibility of primary ciliary dyskinesia, defined as (1) the presence of at least two chronic respiratory symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting primary ciliary dyskinesia. Of the respondents, four completed comprehensive, in-person evaluations, with definitive primary ciliary dyskinesia confirmed in one individual, and probable primary ciliary dyskinesia identified in two others. The high prevalence of respiratory features compatible with primary ciliary dyskinesia in this heterotaxy population suggests that a subset of heterotaxy patients have dysfunction of respiratory, as well as embryonic nodal cilia. To better assess the possibility of primary ciliary dyskinesia, heterotaxy patients with chronic oto-sino-respiratory symptoms should be referred for a primary ciliary dyskinesia evaluation.

原発性線毛運動不全症―最近の進歩

Primary ciliary dyskinesia (PCD) is a hereditary disorder with structural and/or functional impairment of the cilia of the whole body. PCD is characterized by chronic sinusitis, bronchiectasis, male infertility and ectopic pregnancy due to impaired ciliary motility. The prevalence of PCD is estimated at 1 in 20,000 live births. Cases with situs inversus are termed “Kartagener’s syndrome” and usually these diagnoses are not difficult to make. However, in cases without situs inversus, the diagnosis can be very difficult. As such, it is most likely that PCD without situs inversus is underdiagnosed at the present time. The diagnosis of PCD is made when the patients have characteristic clinical features and (1) structural abnormalities of the cilia observed with electron microscopy and/or (2) presence of mutations in one of the genes associated with PCD. Electron microscopic diagnosis is not easy because ultrastructural ciliary defects can also be found in a few cilia among the healthy populations. Measuring levels of nasal nitric oxide (NO) concentration is a very useful tool in screening for PCD, because low NO values are a feature of PCD. Hand-held devices using tidal breathing are as useful as stationary devices. The sensitivity and specificity of nasal NO levels of <250 ppb for diagnosing PCD were 97% and 90%, respectively. Some other features can help to diagnose PCD. Frontal sinuses and sphenoid sinuses are hypoplastic. Having a combination of rhinosinusitis, middle ear and lung diseases increases the probability of PCD. The effectiveness of endonasal sinus surgery to treat rhinosinusitis associated with PCD is controversial.

Growing up with Primary Ciliary Dyskinesia in Bradford, UK: exploring patients experiences as a physiotherapist

Primary Ciliary Dyskinesia (PCD) is a condition which causes impaired mucociliary clearance, resulting in sputum retention and recurrent respiratory tract infections. Physiotherapy, in the form of airway clearance techniques and exercise is recommended to patients with PCD to facilitate sputum clearance. As children diagnosed with PCD develop into adults, understanding their experiences of growing up with this long-term condition and undertaking physiotherapy may help to provide insight to clinicians. No previous research has been published which explores the lived experiences of children and young people with PCD. The prevalence of PCD in Bradford in the North of the UK is unusually high, signifying the importance of understanding the experiences of this patient population. This qualitative study used Interpretive Phenomenological Analysis to allow the researcher, as a physiotherapist, to investigate the lived experiences of five paediatric patients with PCD. While patients’ experiences are all unique, three themes emerged across the analysis of the interviews: (1) the experiences of day to day life with the symptoms and treatment burden of PCD; (2) participants’ awareness of their own symptoms and knowledge of PCD; and (3) the development of mastery skills and devolution of management from the family to the growing child. The results from this study suggested that facilitation of disease acceptance, strategies to increase patient empowerment, the use of patient-centred communication and understanding the contextualisation of patients’ experiences may all help to guide clinical practice.

Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6-8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD.

Treatment and outcomes of chronic rhinosinusitis in children with primary ciliary dyskinesia: where is the evidence? A qualitative systematic review

Consensus on treatment of chronic rhinosinusitis (CRS) in children with primary ciliary dyskinesia (PCD) is limited. We sought to synthesize the best available evidence pertaining to treatment and outcomes of CRS in children with PCD. This work is a systematic review of PubMed and EMBASE for studies pertaining to treatment and outcomes of CRS in children with PCD in a 20-year period. Two reviewers independently extracted information on study design, setting, medical or surgical therapy for CRS, and treatment outcomes. Twelve studies from 8 countries were included for analysis: (3 retrospective cohorts, 2 prospective cohorts, 2 cross-sectional, 1 case series, and 4 case reports). The number of patients with PCD ranged from 1 to 78. Medical treatment included oral antibiotics, intranasal steroids, and oral steroids. Surgical treatment was mentioned in 8 studies, with endoscopic sinus surgery (ESS) described in 3 of 8. Outcome measures were rarely defined but included the 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaire (1/12), symptom questionnaire (1/12), decreased recurrent pneumonia (1/12), and subjective report of CRS symptoms. No randomized, controlled, or long-term prospective cohort studies were identified, and no study employed a disease-specific, pediatric-validated instrument to measure outcomes of therapy. There is a paucity of evidence pertaining to CRS treatment or outcomes in children with PCD. Given the rare prevalence of PCD and the insufficient evidence pertaining to treatment effectiveness for CRS, we propose an international, multicenter database to prospectively track data pertaining to diagnosis, treatment, and outcomes of CRS for children with PCD. This effort would encourage implementation of validated and standardized outcome measures.