Variations in infection control practices suggest a need for guidelines in primary ciliary dyskinesia patient care.

Primary ciliary dyskinesis (PCD) is an autosomal recessive disorder associated with impaired mucociliary clearance caused by defects in ciliary structure and function. The major clinical feature of PCD is recurring or persistent respiratory tract infection. Respiratory tract colonization with drug-resistant organisms impacts the frequency of infections and lung function decline. Protective gear has been employed by caregivers in an attempt to control respiratory tract bacterial spread between patients with cystic fibrosis, but use in PCD is not known. We conducted a web-based survey to investigate infection control and prevention practices of PCD centers in North America, and how practices have been influenced by the COVID-19 pandemic. The response rate was 87.0%. Before the COVID-19 pandemic, glove, gown, and mask use were variable, and only 3.7% of centers used masks during encounters with PCD outpatients. After COVID-19 mandates are lifted, 48.1% of centers plan to continue to use masks during outpatient care, while the practice regarding the use of gloves and gowns was not influenced by the current pandemic. There is no uniform practice for infection control in PCD care indicating the need for practice guidelines. Mitigation of respiratory virus transmission learned during the COVID-19 pandemic may impact future infection control approaches used for patients with PCD and other lung diseases.

Nasopharyngeal carcinoma in a child with Kartagener`s syndrome.

BACKGROUND: Kartagener`s syndrome, a subgroup of primary ciliary dyskinesia, is characterized by situs inversus totalis, chronic sinusitis and bronchiectasis. To date, the association of malignant diseases and Kartagener`s syndrome has been reported and all cases except angioimmunoblastic T cell lymphoma in a child have been seen in adulthood. CASE: A 10-year-old boy who was followed with the diagnosis of Katagener`s syndrome, presented with a progressive mass in the cervical region for 6 months. Physical examination revealed mental retardation, multiple lymphadenopathies, the largest in the left cervical region (4x4 cm), and pectus carinatum. Also, on cardiovascular examination, apex beat was felt on the right fifth intercostal space along midclavicular line. Magnetic resonance imaging of nasopharynx showed narrowing of the nasopharyngeal airway with an increase in wall thickness up to 2.5 cm on the posterior wall of the nasopharynx. Also, bilateral multiple cervical lymphadenopathies were noted. The pathological examination of the biopsy from cervical lymphadenopathy revealed a diagnosis of undifferentiated nasopharyngeal carcinoma. Chemotherapy was started for nasopharyngeal carcinoma chemotherapy regimen including cisplatin, docetaxel, and 5-fluorouracil. After four cycles of chemotherapy there was a significant regression in nasopharyngeal mass and lymphadenopathies. The patient underwent radiotherapy to the nasopharynx and bilaterally cervical regions. The patient has been in follow-up for 6 years well and tumor free. However, he is still under the supervision of the pediatric immunology and allergy departments due to recurrent respiratory infections and sinusitis. CONCLUSION: We present a case of nasopharyngeal carcinoma which developed in a child with Kartagener`s syndrome. To our knowledge, this is the first report of nasopharyngeal carcinoma in a child with Kartagener`s Syndrome.

[Management of Primary Ciliary Dyskinesia]. / Management der Primären Ciliären Dyskinesie.

Primary Ciliary Dyskinesia (PCD, MIM 242650) is a rare, hereditary multiorgan disease characterized by malfunction of motile cilia. Hallmark symptom is a chronic airway infection due to mucostasis leading to irreversible lung damage that may progress to respiratory failure. There is no cure for this genetic disease and evidence-based treatment is limited. Until recently, there were no randomized controlled trials performed in PCD, but this year, data of the first placebo-controlled trial on pharmacotherapy in PCD were published. This cornerstone in the management of PCD was decisive for reviewing currently used treatment strategies. This article is a consensus of patient representatives and clinicians, which are highly experienced in care of PCD-patients and provides an overview of the management of PCD. Treatments are mainly based on expert opinions, personal experiences, or are deduced from other lung diseases, notably cystic fibrosis (CF), COPD or bronchiectasis. Most strategies focus on routine airway clearance and treatment of recurrent respiratory tract infections. Non-respiratory symptoms are treated organ specific. To generate further evidence-based knowledge, other projects are under way, e. g. the International PCD-Registry. Participating in patient registries facilitates access to clinical and research studies and strengthens networks between centers. In addition, knowledge of genotype-specific course of the disease will offer the opportunity to further improve and individualize patient care.

[Primary Ciliary Dyskinesia - Interdisciplinary Diagnostics and Therapy]. / Primäre Ziliendyskinesie (PCD) ­ interdisziplinäre Diagnostik und Therapie.

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.

Diagnóstico de la discinecia ciliar primaria / Diagnosis of the primary ciliary dyskinesia

Primary ciliary dyskinesia is a congenital disorder due to abnormal motile ciliary function, especially in the airway epithelium. The mucociliary clearance is impaired, producing reoccurring respiratory tract infections, usually resulting in bronchiectasis as an adult. Patients also have frequent ear and sinus infections and almost 50% of them have situs inversus. Diagnosis of primary ciliary dyskinesia is difficult because there is not a single gold standard test, resulting in the need of a multi-test approach. Until recently in our country we only had transmission electron microscopy, but nasal nitric oxide and high speed video microscopy are now available. In this article we will detail the most important clinical characteristics that make us suspect the presence of primary ciliary dyskinesia at different ages and the methods available for its diagnosis.

La discinesia ciliar primaria es una enfermedad congénita debida a una alteración del movimiento normal de los cilios, especialmente a nivel del epitelio respiratorio. Esto se traduce en una alteración del clearance mucociliar lo que predispone al paciente a tener infecciones respiratorias repetidas, terminando en la aparición de bronquiectasias en la edad adulta. También son frecuentes las infecciones repetidas de oídos y cavidades perinasales. La presencia de situs inverso puede verse en hasta en 50% de los pacientes con esta enfermedad. El diagnóstico de discinesia ciliar primaria es difícil ya que no existe un examen que sea considerado patrón de oro, por lo que se requiere la realización de distintos exámenes. En nuestro país hasta hace poco tiempo solo contábamos con la microscopía electrónica, pero recientemente se ha sumado la medición de óxido nítrico nasal y la videomicroscopía de alta velocidad. En el presente artículo se detallarán las características clínicas más importantes que hacen sospechar la presencia de DCP en las distintas edades y los métodos disponibles para su diagnóstico.

Tratamiento de la discinecia ciliar primaria / Treatmen of ciliary primary discinesia

At present, there is no specific treatment for primary ciliary dyskinesia, nor controlled and randomized clinical trials to determine how the management and monitoring of these patients should be considered. The therapeutic options are extrapolated from other diseases, such as cystic fibrosis, or non-cystic fibrosis bronchiectasis. However, the implementation of specific groups of experts, both in the USA (PDC-foundation) and in Europe (BESTCILIA or BEAT-PD), are helping to increase knowledge of the disease, opening research channels and seeking new treatments. Until we have therapies capable of correcting the basic defect of the disease, the pillars of treatment are the daily cleansing of the airways and aggressive antibiotherapy against respiratory infections. Multidisciplinary care in specialized centers where pulmonary function is monitored and the infection is prevented and treated will improve, as in cystic fibrosis, the results of patients.

En la actualidad no existe un tratamiento específico para la discinesia ciliar primaria, ni se cuenta con ensayos clínicos controlados y randomizados que permitan determinar cómo debe plantearse el manejo y seguimiento de estos pacientes. Las opciones terapéuticas son extrapoladas de otras enfermedades, como la fibrosis quística, o las bronquiectasias no fibrosis quística. Sin embargo, la puesta en marcha de grupos específicos de expertos, tanto en USA (PDC-foundation) como en Europa (BESTCILIA o BEAT-PD), están permitiendo incrementar el conocimiento de la enfermedad, abriendo vías de investigación y buscando nuevos tratamientos. Hasta contar con terapias capaces de corregir el defecto básico de la enfermedad, los pilares del tratamiento son la limpieza diaria de las vías aéreas y la antibioterapia agresiva frente a las infecciones respiratorias. La atención multidisciplinar en centros especializados donde se monitorice la función pulmonar y se prevengan y traten las infecciones mejorará, como en la fibrosis quística, los resultados de los pacientes.

Kartagener's syndrome: a case report.

BACKGROUND: Kartagener's syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive inherited disorder characterized by the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. Abnormal ciliary structure or function leading to impaired ciliary motility is the main pathophysiologic problem in Kartagener's syndrome. CASE PRESENTATION: A 24-year-old man from Gondar town, North-West Ethiopia, presented to University of Gondar Hospital with recurrent episodes of nasal congestion with itching and paranasal discomfort, and productive cough for more than a decade. Clinical and imaging findings revealed chronic sinusitis, bronchiectasis, dextrocardia, and situs inversus. He was treated with orally administered antibiotics, mucolytic, and chest physiotherapy. He was symptomatically better with the above therapy, and started on a long-term low-dose prophylactic antibiotic. CONCLUSIONS: Patients with Kartagener's syndrome exist in Ethiopia as cases of chronic recurrent sinopulmonary infections. As there is no easy, reliable non-invasive diagnostic test for Kartagener's syndrome and the correct diagnosis is often delayed by years, it may cause chronic respiratory problems with reduced quality of life. Genetic counseling and fertility issues should be addressed once Kartagener's syndrome is diagnosed.

Airway Clearance Techniques for Primary Ciliary Dyskinesia; is the Cystic Fibrosis literature portable?

Primary Ciliary Dyskinesia (PCD) is a rare inherited disease with impaired mucociliary clearance. Airway clearance techniques (ACTs) are commonly recommended for patients with PCD to facilitate mucus clearance, despite a lack of evidence in this group. Current physiotherapy practice in PCD is based on evidence extrapolated from the field of Cystic Fibrosis (CF). This paper focuses on the available evidence and outlines challenges in extrapolating evidence between the conditions for best clinical practice.

Clinical care of children with primary ciliary dyskinesia.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disorder, usually inherited as an autosomal recessive condition but X-linked inheritance is also described. Abnormal ciliary function in childhood leads to neonatal respiratory distress in term infants, persistent wet cough, bronchiectasis, chronic rhinosinusitis, and hearing impairment; approximately 50% of patients have situs inversus. There is a paucity of evidence for treating PCD, hence consensus guidelines are predominantly influenced by knowledge from cystic fibrosis (CF). Extrapolation of evidence from other diseases is inappropriate since differences in pathophysiology, morbidity and prognosis risk treatment failure and lack of adherence. Areas covered: Review authors searched PubMed and Cochrane databases for publications relating to management of children with PCD. Because of the paucity of data, we emphasise the need for well-designed clinical trials with PCD patients rather than reliance on evidence from other diseases. Expert commentary: The evidence for treatment of PCD is poor, and management is often extrapolated from studies of patients with CF or chronic rhinosinusitis. However, much work is underway to improve the situation and international consortia and networks are conducting well-designed projects to inform the management of children with PCD.

Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries.

Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise.In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics). We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.

[Zivert-Kartagener's syndrome encountered in the practical work of an otorhionolaryngologist, pulmonologist, obstetrician, and gynecologist]. / Sindrom Ziverta­Kartagenera v praktike LOR-vracha, pul'monologa i akushera-ginekologa.

The objective of the present work was to analyze the current concept of the genetically predetermined condition Zivert-Kartagener's syndrome with special reference to the pathogenetic mechanisms underlying the development of this condition, its clinical picture and methods of treatment. The authors' original observations of the patients presenting with Zivert-Kartagener's syndrome are reported.

Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disorder characterised by dysfunction of motile cilia. Ciliary dysmotility causes poor mucociliary clearance and leads to impairment of pulmonary function and severe respiratory infections. PCD has no specific therapy. With the aim to permanently restore gene function and normalise ciliary motility, we used gene editing to replace mutated with wild-type sequence in defective cells. METHODS: The target gene was dynein heavy chain 11 (DNAH11), an essential component of ciliary structure. Airway ciliated cells were collected from two patients with PCD with DNAH11 nonsense mutations and altered ciliary beating and pattern. Repair of the genetic defect was performed ex vivo by site-specific recombination using transcription activator-like effector nucleases (TALENs). RESULTS: In an epithelial cell line engineered to contain the DNAH11 target site, TALENs cleaved over 80% of the mutated DNAH11 sequence and replaced the mutated sequence with wild-type sequence in about 50% of cells. In airway ciliated cells of patients with PCD, site-specific recombination and normalisation of ciliary beating and pattern occurred in 33% and 29% of cells, respectively. CONCLUSION: This study demonstrates that gene editing can rescue ciliary beating ex vivo, opening up new avenues for treating PCD.

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.

Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung disease resulting in chronic oto-sino-pulmonary disease in both children and adults. Many physicians incorrectly diagnose PCD or eliminate PCD from their differential diagnosis due to inexperience with diagnostic testing methods. Thus far, all therapies used for PCD are unproven through large clinical trials. This review article outlines consensus recommendations from PCD physicians in North America who have been engaged in a PCD centered research consortium for the last 10 years. These recommendations have been adopted by the governing board of the PCD Foundation to provide guidance for PCD clinical centers for diagnostic testing, monitoring, and appropriate short and long-term therapeutics in PCD patients.

Treatment recommendations in Primary Ciliary Dyskinesia.

Primary Ciliary Dyskinesia (PCD) is a rare heterogenic disorder leading to significant respiratory morbidity. Health-care providers who treat PCD must familiarize themselves with recommended treatment strategies. However, most of the treatments recommended in PCD have been extrapolated from cystic fibrosis (CF) and non-CF bronchiectasis literature. Mainstays of therapy are reviewed in detail, and should include at a minimum: regular airway clearance, routine microbiological surveillance, antibiotic treatment for pulmonary exacerbation, and health vaccinations. This review summarizes both medical and surgical pulmonary treatment considerations, as well as recommendations for the integration of non-pulmonary subspecialty care in the management of PCD.

Primary ciliary dyskinesia in adults.

INTRODUCTION: Primary ciliary dyskinesia is an autosomal recessive genetic disorder leading to structural and/or functional abnormalities of motor cilia. Impaired mucociliary clearance is responsible for the development of a multi-organ disease, which particularly affects the upper and lower airways. STATE OF THE ART: In adults, primary ciliary dyskinesia is mainly characterized by bronchiectasis and chronic ear and sinus disorders. Situs inversus is found in half of patients and fertility disorders are commonly associated. Diagnosis is based on specialized tests: reduced level of nasal nitric oxide concentrations is suggestive of primary ciliary dyskinesia, but only a nasal or bronchial biopsy/brushing with analysis of beat pattern by videomicroscopy and/or analysis of cilia morphology by electronic microscopy can confirm the diagnosis. However, the diagnosis is difficult to achieve due to the limited access to these specialized tests and to difficulties in interpreting them. Genetic tests are under development and may provide new diagnostic tools. Treatment is symptomatic, based on airway clearance techniques (e.g., physiotherapy) and systemic and/or inhaled antibiotics. Prognosis is related to the severity of the respiratory impairment, which can be moderate or severe. PERSPECTIVES AND CONCLUSIONS: Diagnosis and management of primary ciliary dyskinesia remain poorly defined and should be supported by specialized centers to standardize the diagnosis, improve the treatment and promote research.

Primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder of cilia structure, function, and biogenesis leading to chronic infections of the respiratory tract, fertility problems, and disorders of organ laterality. The diagnosis can be challenging, using traditional tools such as characteristic clinical features, ciliary function, and ultrastructural defects and newer screening tools such as nasal nitric oxide levels and genetic testing add to the diagnostic algorithm. There are 32 known PCD-causing genes, and in the future, comprehensive genetic testing may screen young infants before developing symptoms, thus improving survival. Therapies include surveillance of pulmonary function and microbiology, in addition to airway clearance, antibiotics, and early referral to bronchiectasis centers. As with cystic fibrosis (CF), standardized care at specialized centers using a multidisciplinary approach likely improves outcomes. In conjunction with the CF foundation, the PCD foundation, with experienced investigators and clinicians, is developing a network of PCD clinical centers to coordinate the effort in North America and Europe. As the network grows, clinical care and knowledge will improve.

Primary ciliary dyskinesia: overlooked and undertreated in children.

Primary ciliary dyskinesia (PCD) is a multi-organ disorder associated with chronic oto-sino-pulmonary disease, neonatal respiratory distress, situs abnormalities and reduced fertility. Repeated respiratory tract infections leads to the almost universal development of bronchiectasis. These clinical manifestations are a consequence of poorly functioning motile cilia. However, confirming the diagnosis is quite difficult and is often delayed, so the true incidence of PCD may be significantly higher than current estimates. Nasal nitric oxide has been earmarked as a useful screening tool for identifying patients, but its use is limited in pre-school-aged children. Due to the rarity of PCD, the evidence base for management is somewhat limited, and treatment regimens are extrapolated from other suppurative lung disorders, like cystic fibrosis.

Kartagener's syndrome and rheumatoid arthritis.

We herein present the case of a 47-year-old woman with rheumatoid arthritis (RA) complicated by Kartagener's syndrome (KS). Although her RA disease activity score (DAS28-CRP) decreased following the administration of periodontitis treatment and etanercept, she did not achieve symptom relief or DAS28-CRP remission. After undergoing surgery for chronic sinusitis, her articular symptoms improved and the DAS28-CRP declined to the level of remission. Patients with KS may develop respiratory infections due to an impaired defense mechanism against microbes in the airway. Therefore, in patients with RA complicated by KS, comprehensive management of infection, including surgical therapy for sinusitis, is needed to reduce the RA disease activity.

Primary ciliary dyskinesia complicated with diffuse panbronchiolitis: a case report and literature review.

BACKGROUND: Fifty percent of patients with primary ciliary dyskinesia (PCD) have situs inversus. Diffuse panbronchiolitis (DPB) might be one of the characteristic features of the lung in PCD. METHODS: We reported a case of PCD without situs inversus, yet complicated with DPB, and did literature review. RESULTS: A 34-year-old nonsmoking Chinese woman with 6-year primary infertility suffered from recurrent episodes of respiratory tract infections since childhood. Lung auscultation revealed end-inspiratory coarse crackles. Pulmonary function tests demonstrated mild obstructive ventilation functional impairment. Lung biopsy showed respiratory bronchiolitis. Nasal mucosa cilia showed the absence of both outer and inner dynein arms of the microtubules. Saccharin test was positive. Chest images showed bronchiectasis and bronchiolitis but no situs inversus. Paranasal sinus computed tomography (CT) showed maxillary sinusitis and ethmoid sinusitis. A culture of bronchoalveolar lavage fluid was positive for Pseudomonas aeruginosa. Her conditions improved in clinical symptoms and CT images after 2 months of treatment with azithromycin. Literature review revealed that very rare patients were diagnosed as PCD complicated with diffuse DPB, and all of them had situs inversus. CONCLUSIONS: The association of DPB might be one of the characteristic features of the lung in PCD. Further studies on the concurrence of these two diseases are suggested so as to elucidate the mechanism of both.