Management Of Primary Ciliary Dyskinesia Research Articles

Primary ciliary dyskinesia diagnosis and management and its implications in America: a mini review.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder that can result in significant morbidity and mortality if left untreated. Clinical manifestations of PCD include recurrent respiratory infections, laterality defects, and infertility, all of which arise from impaired or absent ciliary motility. Diagnostic approaches for PCD may include high-speed video microscopy, measurement of nasal nitric oxide levels, and genetic testing; however, no single definitive diagnostic test exists. The present study aims to highlight the lack of standardized diagnostic and treatment guidelines for PCD in Latin America (Central and South America, and the Caribbean). To this effect, we compared North American and European recommendations for the diagnosis and management of PCD and found that certain diagnostic tools and treatment options mentioned in these guidelines are not readily accessible in many Latin American countries. This review gathers disease information in North America, Europe, and Latin America organizing guideline results into tables for clarity and potential interventions. Management information for Latin America is inferred from case reports, as most findings are from North American recommendations and studies on PubMed, Google Scholar, and Scopus. Treatment and management information is based on North American and European standards.Among 5,774 publications reviewed, only 15 articles met the inclusion criteria (focused on PCD management, peer-reviewed, and located in America). No clinical guideline for PCD in Latin America was found, but recommendations on respiratory management from Colombia and Chile were discovered. The lack of guidelines in Latin America may originate from limited resources and research on the disease in those countries. PCD lacks documentation, research, and recommendations regarding its prevalence in Latin America, likely due to unfavorable economic conditions. This disadvantage results in limited access to diagnostic tests available in North America and Europe. The PICADAR score, discussed in this review, can be used in low-income nations as a screening tool for the disorder.

Characteristics of Otologic Disease Among Patients With Primary Ciliary Dyskinesia

Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity. To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort. This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included. Potential risk factors associated with increased risk of ear disease. The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment. A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91). In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is an inherited cause of bronchiectasis. The estimated PCD prevalence in children with bronchiectasis is up to 26% and in adults with bronchiectasis is 1 to 13%. Due to dysfunction of the multiple motile cilia of the respiratory tract patients suffer from poor mucociliary clearance. Clinical manifestations are heterogeneous; however, a typical patient presents with chronic productive cough and rhinosinusitis from early life. Other symptoms reflect the multiple roles of motile cilia in other organs and can include otitis media and hearing loss, infertility, situs inversus, complex congenital heart disease, and more rarely other syndromic features such as hydrocephalus and retinitis pigmentosa. Awareness, identification, and diagnosis of a patient with PCD are important for multidisciplinary care and genetic counseling. Diagnosis can be pursued through a multitest pathway which includes the measurement of nasal nitric oxide, sampling the nasal epithelium to assess ciliary function and structure, and genotyping. Diagnosis is confirmed by the identification of a hallmark ultrastructural defect or pathogenic mutations in one of > 45 PCD causing genes. When a diagnosis is established management is centered around improving mucociliary clearance through physiotherapy and treatment of infection with antibiotics. The first international randomized controlled trial in PCD has recently been conducted showing azithromycin is effective in reducing exacerbations. It is likely that evidence-based PCD-specific management guidelines and therapies will be developed in the near future. This article examines prevalence, clinical features, diagnosis, and management of PCD highlighting recent advances in basic science and clinical care.

New Diagnostic Methods and Treatment Recommendations in Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare and genetically heterogeneous disease and clinically characterized by neonatal respiratory distress, organ laterality defects, persistent rhinosinusitis, chronic bronchitis, and eventually bronchiectasis. Currently, there is no single “gold standard” diagnostic test for PCD. PICADAR (Primary Ciliary Dyskinesia Rule) score is a guide to decide for further evaluation of diagnostic tests in PCD. European Respiratory Society (ERS) and American Thoracic Society (ATS) recommend diagnostic tests, including nasal nitric oxide (nNO), high-speed video analysis (HSVMA), transmission electron microscopy (TEM) and genetic testing. Cryo-electron tomography and immunofluorescence methods are new techniques recently performed by specialized centers and needs to be improved. Age at diagnosis for PCD changes according to awareness of disease and available diagnostic tests in different centers. Regular follow-up and multidisciplinary approach is important in the management of PCD. The main aim of the treatment is to prevent pulmonary exacerbations and slow the progression of the disease since there are no treatment approaches to correct the underlying cilia structure and its functions in PCD. Although, there are not enough randomized controlled trials for the treatment of PCD, recent treatments are usually based on to improve the mucociliary clearance. Early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression leading to bronchiectasis and lung function impairment in PCD

Primary Ciliary Dyskinesia - Interdisciplinary Diagnostics andTherapy

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease. First respiratory symptoms already occur within the first hours after birth. Major symptoms are an unexplained neonatal respiratory distress syndrome, situs inversus, persistant cough, and chronic nasal congestion, recurrent paranasal sinus disorders with or without polyps, bronchiectasis as well as male infertility. Diagnostics is complex and includes transmission electron microscopy, nasal NO assessment, high-speed video microscopy and genetic evaluations. This review gives an overview over the current diagnostic procedures and therapeutic options. The management of PCD is a multidisciplinary approach, which should be reserved to in highly specialized centers.

Clinical features and management of children with primary ciliary dyskinesia in England

ObjectiveIn England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children...

Variation in treatment strategies for the eradication of Pseudomonas aeruginosa in primary ciliary dyskinesia across European centers.

Primary ciliary dyskinesia (PCD) is a rare disease causing motile cilia dysfunction, recurrent airway infection, and bronchiectasis. Airway infection management strategies are borrowed from cystic fibrosis. The aim of this study is to describe the management of airway infection with Pseudomonas aeruginosa (PA) in children and adults with PCD across European centers. An online survey questionnaire was sent electronically using SurveyMonkey® to 55 PCD centers in 36 European countries. Fifty-two responded from 43 centers in 26 countries, a response rate of 70%. Most (89%) countries did not have written guidelines for PCD management. Airway sampling for infection detection at each clinic visit was more likely when follow-up was frequent. Eighty-seven percent of centers chose to treat the first PA isolate, most prescribing combined oral ciprofloxacin and inhaled colistimethate sodium (43%, n = 18). The preferred treatment for chronic infection with PA was nebulized colistimethate in 51% (n = 22). In summary, considerable variation exists across European centers in the frequency of patient follow-up and airway sampling for infection, treatment goals, and the management of PA infection. Few centers had written guidelines for PCD management. Clinical trials to determine optimal treatment of PA in PCD patients are urgently needed.

Diagnosis and management of children with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare, genetic disorder of the motile cilia characterised by chronic lung disease, nasal and sinus disease, chronic ear infections with glue ear leading to possible hearing impairment, and subfertility. Half of patients have organ laterality defects. Despite symptoms being present from birth, PCD remains underdiagnosed. Early diagnosis and symptom management may reduce morbidity, improve quality of life and ensure children are adequately supported to meet their full potential. This article seeks to raise awareness of PCD in children's nurses who are well placed to identify children for referral to the national PCD diagnostic service. It examines the clinical characteristics of the disease along with the complexities and limitations of diagnostic testing. In addition, it explores the management of children with PCD within the national PCD management service for children.

Study protocol, rationale and recruitment in a European multi-centre randomized controlled trial to determine the efficacy and safety of azithromycin maintenance therapy for 6 months in primary ciliary dyskinesia

BackgroundClinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD. Maintenance therapy, with the macrolide antibiotic azithromycin, is currently widely used in chronic respiratory diseases including PCD. In addition to its antibacterial properties, azithromycin is considered to have beneficial anti-inflammatory and anti-quorum-sensing properties.The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory exacerbations in PCD. The secondary objectives are to evaluate the efficacy of azithromycin on lung function, ventilation inhomogeneity, hearing impairment, and symptoms (respiratory, sinus, ears and hearing) measured on a PCD-specific health-related quality of life instrument, and to assess the safety of azithromycin maintenance therapy in PCD.MethodsThe BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months. Subjects with a confirmed diagnosis of PCD, age 7–50 years, are eligible for inclusion. Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria are exclusion criteria. The planned number of subjects to be included is 125. The trial has been approved by the Research Ethics Committees of the participating institutions.DiscussionWe present a study protocol of an ongoing RCT, evaluating for the first time, the efficacy and safety of a pharmacotherapeutic treatment for patients with PCD. The RCT evaluates azithromycin maintenance therapy, a drug already commonly prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment, and the patients’ perception of disease severity and necessity of additional management and treatment during trial participation.Trial registrationEudraCT 2013-004664-58 (date of registration: 2014-04-08).

Hypovitaminosis D: a novel finding in primary ciliary dyskinesia.

BackgroundA relationship between low levels of serum vitamin D and respiratory infections has been established. No study has examined the frequency and clinical relevance of vitamin D deficiency in patients with primary ciliary dyskinesia (PCD).MethodsVitamin D levels were measured in 22 PCD patients (7 females, 10.5 years, range, 2–34 years). In PCD, pulmonary function tests (PFTs), sputum microbiology, self-reported physical activity (PA) level, and quality of life (QoL) by means of the Saint George’s Respiratory Questionnaire (SGRQ), were also assessed.ResultsSeventy-two percent of PCD patients were vitamin-D deficient-to-insufficient and 28% were sufficient. No differences in PFTs parameters were found between vitamin D deficiency-to-insufficiency and sufficiency groups. Patients with vitamin D deficiency-to-insufficiency had significantly higher SGRQ total scores, and thus poorer QoL (p = 0.03). Seventy-nine percent of PCD subjects had limitations in performing vigorous activities, and 53% performed less than 3 hours of PA per week. Vitamin D deficiency-to-insufficiency and sufficiency groups did not show any differences in age at PCD diagnosis or at onset of respiratory symptoms, BMI, atopy, current asthma or bronchiectasis. However, 79% of patients with bronchiectasis had vitamin D deficiency-to-insufficiency. No differences were found in the rate of positive sputum cultures and in the number of antibiotic courses between the two groups.ConclusionsHypovitaminosis D is common in PCD patients, and is associated with poorer QoL. We recommend the assessment and treatment of hypovitaminosis D to be included in the routine management of PCD.

Diagnosis and management of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder with defective structure and/or function of motile cilia/flagella, causing chronic upper and lower respiratory tract infections, fertility problems, and disorders of organ laterality. Diagnosing PCD requires a combined approach utilizing characteristic phenotypes and complementary methods for detection of defects of ciliary function and ultrastructure, measurement of nasal nitric oxide and genetic testing. Currently, biallelic mutations in 31 different genes have been linked to PCD allowing a genetic diagnosis in approximately ~ 60% of cases. Management includes surveillance of pulmonary function, imaging, and microbiology of upper and lower airways in addition to daily airway clearance and prompt antibiotic treatment of infections. Early referral to specialized centers that use a multidisciplinary approach is likely to improve outcomes. Currently, evidence-based knowledge on PCD care is missing let alone management guidelines. Research and clinical investigators, supported by European and North American patient support groups, have joined forces under the name of BESTCILIA, a European Commission funded consortium dedicated to improve PCD care and knowledge. Core programs of this network include the establishment of an international PCD registry, the generation of disease specific PCD quality of life questionnaires, and the first randomized controlled trial in PCD.

Primary Ciliary Dyskinesia: An Update on New Diagnostic Modalities and Review of the Literature

Primary ciliary dyskinesia (PCD) is a genetic condition affecting approximately 1 in 15,000-20,000 individuals, and the majority of cases exhibit an autosomal recessive inheritance pattern. However, genetic heterogenicity is seen in PCD and reflects the complexity of ciliary structure and biogenesis. There have been many recent advances in the diagnosis and management of PCD in the last few years, including advanced genetic sequencing, nasal nitric oxide assay, and ciliary motility tests. This article focuses on the ultrastructure and pathophysiology of ciliary dyskinesias, along with a review of clinical features, screening, and diagnostic tests. It also reflects upon the diagnostic challenge caused by the diverse clinical presentation, which will be of great value to pediatricians for considering PCD in their differential list, henceforth leading to early recognition and management, along with awareness of the recent advances in the field of genetics and other techniques for diagnosis of this condition.

Multicenter analysis of body mass index, lung function, and sputum microbiology in primary ciliary dyskinesia

No studies longitudinally, simultaneously assessed body mass index (BMI) and spirometry in primary ciliary dyskinesia (PCD). We determined BMI and spirometry in 158 PCD children and adolescents from London, UK (n = 75), Naples, Italy (n = 23) and Copenhagen, Denmark (n = 60) at first presentation and during follow-up. Annual BMI and spirometry were prospectively collected and analyzed over blocks of 2, 4, and 6 consecutive years. Sputum pathogens were recorded. Age at first spirometry was 8.7 years (range, 4.2-17.4). Mean Z scores of first measured BMI, FEV1, FVC, and FEF(25-75) were 0.01, -1.37, -0.84, and -1.68, respectively. First spirometry was not more frequently impaired in patients referred at age ≥6 years than in those referred at preschool age (P = 0.13). There were no differences in slopes for BMI, FEV1, FVC, or FEF(25-75) over any time block. H. influenzae was the most common pathogen, isolated at least once in 65% of patients. P. aeruginosa was found in 58 subjects (37%) of whom 8 (5%) were chronically infected. Neither pathogens was associated with spirometry changes. Preschool referral to a PCD center was not associated with better spirometry or BMI. PCD children and adolescents receiving centralized care show steady BMI and spirometry during medium term follow-up. There was a high prevalence of Pseudomonas aeruginosa infection, but the evolution of spirometry or BMI was not affected by this microorganism in medium term. Despite our longitudinal analysis showed no differences between the three centers, the assessment of spirometry and BMI over time represents a quality improvement tool. Future studies are needed to highlight the role of spirometry and BMI in long term PCD management and identify subgroups of patients with a higher risk of early lung failure or nutritional problems.

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.

Overcoming challenges in the management of primary ciliary dyskinesia: The UK model

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease associated with bronchiectasis, chronic rhinosinusitis, infertility and situs inversus. Estimates of prevalence vary widely, but is probably between 1:10,000- 1:40,000 in most populations. A number of observational studies indicate that access to services to diagnose and manage patients with PCD vary both between and within countries. Diagnosis is often delayed and frequently missed completely. The prognosis of patients with PCD is variable, but evidence suggests that it is improved by early diagnosis and specialist care. This article briefly reviews the literature concerning PCD and the evidence that specialist care will improve healthcare outcomes. The article specifically refers to a new national service in the UK.

Management of primary ciliary dyskinesia in European children: recommendations and clinical practice

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2-9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country's general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.

Spectrum of Clinical Diseases Caused By Disorders of Primary Cilia

The ciliopathies are a category of diseases caused by disruption of the physiological functions of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal, hepatic, and pancreatic cyst formation; situs abnormalities; retinal degeneration; anosmia; cerebellar or other brain anomalies; postaxial polydactyly; bronchiectasis; and infertility. The specific clinical features are dictated by the subtype, structure, distribution, and function of the affected cilia. This review highlights the clinical variability caused by dysfunction of motile and nonmotile primary cilia and emphasizes the genetic heterogeneity and phenotypic overlap that are characteristics of these disorders. There is a need for additional research to understand the shared and unique functions of motile and nonmotile cilia and the pathophysiology resulting from mutations in cilia, basal bodies, or centrosomes. Increased understanding of ciliary biology will improve the diagnosis and management of primary ciliary dyskinesia, syndromic ciliopathies, and cilia-related cystic diseases.

Diagnosis and management of primary ciliary dyskinesia

Diagnosis and management of primary ciliary dyskinesia

Diagnosis and management of primary ciliary dyskinesia

Primary ciliary dyskinesia is a rare inherited condition affecting the movement and structure of the cilia in various areas of the body, including sinuses, ears and airways. Since 2006, three centres for diagnosis and research in England have been raising awareness and funding for primary ciliary dyskinesia's diagnosis and treatment. Other areas in the UK have their own arrangements and can refer to one of the English centres. This article discusses the condition, introduces the centres and advises on where to get more information. The author concludes that paediatric nurses are in a unique position to learn about and increase awareness of the condition to help prevent unnecessary ear, nose and throat surgeries and permanent lung damage.

Management of primary ciliary dyskinesia: the lower airways

Primary ciliary dyskinesia (PCD) is a genetic disease associated with defective ciliary structure and function. Chronic oto-sino-pulmonary infection is the most common clinical presentation. Patients should be monitored in centres with expertise in PCD. Regular respiratory monitoring consists of lung function tests, adapted to the patient's age, and cough swab or sputum cultures. Chest X-rays are insensitive but the use of high-resolution computed tomography should be considered carefully to avoid excessive radiation. Treatment of the chronic suppuration of the lower airways relies on antibiotics to which the isolated bacteria are sensitive, together with respiratory physiotherapy and exercise to clear excessive bronchial secretions. Bronchodilators and anti-inflammatory agents have no proven benefit and should be prescribed, if at all, on an individual basis. Treatment of the lower airways should always be in conjunction with that of the upper airways. Importantly in PCD, respiratory disease may be controlled with the use of early, adequate and aggressive management.