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Texas Heart Institute Journal Jun 2016Platypnea-orthodeoxia syndrome is a rare disease defined by dyspnea and deoxygenation, induced by an upright position, and relieved by recumbency. Causes include... (Review)
Review
Platypnea-orthodeoxia syndrome is a rare disease defined by dyspnea and deoxygenation, induced by an upright position, and relieved by recumbency. Causes include shunting through a patent foramen ovale and pulmonary arteriovenous malformations. A 79-year-old woman experienced 2 syncopal episodes at rest and presented at another hospital. In the emergency department, she was hypoxic, needing 6 L/min of oxygen. Her chest radiograph showed nothing unusual. Transthoracic echocardiograms with saline microcavitation evaluation were mildly positive early after agitated-saline administration, suggesting intracardiac shunting. She was then transferred to our center. Right-sided heart catheterization revealed no oximetric evidence of intracardiac shunting while the patient was supine and had a low right atrial pressure. However, her oxygen saturation dropped to 78% when she sat up. Repeat transthoracic echocardiography while sitting revealed a dramatically positive early saline microcavitation-uptake into the left side of the heart. Transesophageal echocardiograms showed a patent foramen ovale, with right-to-left shunting highly dependent upon body position. The patient underwent successful percutaneous patent foramen ovale closure, and her oxygen supplementation was suspended. In patients with unexplained or transient hypoxemia in which a cardiac cause is suspected, it is important to evaluate shunting in both the recumbent and upright positions. In this syndrome, elevated right atrial pressure is not necessary for significant right-to-left shunting. Percutaneous closure, if feasible, is first-line therapy in these patients.
Topics: Aged; Cardiac Catheterization; Cardiac Surgical Procedures; Decision Making; Dextrocardia; Dyspnea; Female; Foramen Ovale, Patent; Heart Septal Defects, Atrial; Humans; Hypoxia; Syndrome
PubMed: 27303248
DOI: 10.14503/THIJ-15-5280 -
Archives of Disease in Childhood Dec 2007Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive disorder and presents with upper and lower respiratory tract infection, and mirror image... (Review)
Review
Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive disorder and presents with upper and lower respiratory tract infection, and mirror image arrangement in around 50% of cases. Cilia dysfunction is also implicated in a wider spectrum of disease, including polycystic liver and kidney disease, central nervous system problems including retinopathy and hydrocephalus, and biliary atresia. Cilia are complex structures, containing more than 250 proteins; recent studies have begun to locate PCD genes scattered throughout the genome. Screening tests for PCD include nasal nitric oxide and in vivo tests of ciliary motility such as the saccharin test. Specific diagnosis requires examination of cilia by light and electron microscopy, with epithelial culture in doubtful cases. This is only available in supra-regional centres, recently centrally funded by the National Commissioning Group. Treatment is not evidence based and recommendations are largely extrapolated from cystic fibrosis and other suppurative lung diseases.
Topics: Adolescent; Adult; Child; Child, Preschool; Cilia; Humans; Infant; Infant, Newborn; Kartagener Syndrome; Opportunistic Infections; Respiration Disorders
PubMed: 17634184
DOI: 10.1136/adc.2006.096958 -
British Heart Journal Nov 1963
Review
Topics: Birth Weight; Consanguinity; Dextrocardia; Embryology; Genetics, Medical; Heart Defects, Congenital; Humans; Levocardia; Seasons; Situs Inversus
PubMed: 14072604
DOI: 10.1136/hrt.25.6.803 -
Proceedings of the American Thoracic... Sep 2011Primary ciliary dyskinesia (PCD) is a rare genetic disorder of ciliary structure and function. The diagnosis can be challenging, particularly when using nongenetic... (Review)
Review
Primary ciliary dyskinesia (PCD) is a rare genetic disorder of ciliary structure and function. The diagnosis can be challenging, particularly when using nongenetic assays. The "gold standard" diagnostic test is ultrastructural analysis of respiratory cilia obtained by nasal scrape or brush biopsy. A few specialized centers use high-speed videomicroscopy to examine ciliary beat. Certain beat patterns correlate with ultrastructural defects, and, in some cases, subtle alterations in beat pattern can be seen when ultrastructure is normal. Recent studies have shown that nasal nitric oxide (NO) is very low in patients with PCD compared with healthy control subjects; therefore, this assay may be a useful screening or adjunctive test for PCD. Because acute respiratory illnesses may yield alterations in ciliary ultrastructure, ciliary beat, and nasal NO values, these tests should be performed during a stable baseline period. Identification of an array of PCD genes has provided the opportunity for making a definitive genetic diagnosis for PCD in some cases. All of these approaches have a role in diagnosing PCD. For example, PCD has been confirmed by identifying disease-causing mutations in a heavy dynein chain gene in individuals with normal ciliary ultrastructure but subtle defects in ciliary beat and low nasal NO. Priorities to improve nongenetic diagnostic capability include standardization of nasal NO as a screening test and the development of specialized centers using uniform approaches for the analysis of ciliary ultrastructure and ciliary beat pattern. Another chapter in this issue (see Zariwala and colleagues, pp. 430) addresses the progress toward improved capabilities for definitive genetic testing.
Topics: Axoneme; Biomarkers; Cilia; Dyneins; Humans; Kartagener Syndrome; Microscopy, Electron; Microscopy, Video; Nasal Cavity; Nitric Oxide
PubMed: 21926395
DOI: 10.1513/pats.201103-028SD -
Microbiology Spectrum Dec 2023PCD is a rare disease characterized by productive cough, rhinitis, and recurrent infections of the upper and lower airways. Because the diagnosis of PCD is often...
PCD is a rare disease characterized by productive cough, rhinitis, and recurrent infections of the upper and lower airways. Because the diagnosis of PCD is often delayed, patients receive more antibiotics, experience a heavier financial burden, and have a worse prognosis; thus, it is very important to identify the pathogeny and use the correct antibiotic. In this large single-center study of PCD microbiota, we identified an outline of the bacterial microbes from the respiratory tract; furthermore, we found that the microbiota diversity in pediatric sputum was richer than that in pediatric BALF through sequencing, indicating a heterogeneous community structure. The microbiota diversity and richness were lower during pulmonary exacerbation than during pulmonary stabilization. A significantly higher abundance of had a moderate distinguishing effect for lung exacerbation, which attracted more attention for the study of therapy in pediatric patients with PCD.
Topics: Humans; Child; Kartagener Syndrome; Lung; Microbiota; Sputum; Anti-Bacterial Agents
PubMed: 37796006
DOI: 10.1128/spectrum.02213-23 -
Genetics in Medicine : Official Journal... May 2023Primary ciliary dyskinesia (PCD) is a heterogeneous disorder that includes respiratory symptoms, laterality defects, and infertility caused by dysfunction of motile...
PURPOSE
Primary ciliary dyskinesia (PCD) is a heterogeneous disorder that includes respiratory symptoms, laterality defects, and infertility caused by dysfunction of motile cilia. Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance.
METHODS
In addition to studies in mouse and planaria, clinical exome sequencing and functional analyses in human were performed.
RESULTS
In this study, we identified homozygous pathogenic variants in CLXN (EFCAB1/ODAD5) in 3 individuals with laterality defects and respiratory symptoms. Consistently, we found that Clxn is expressed in mice left-right organizer. Transmission electron microscopy depicted ODA defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1, and DNAI2 from the distal axonemes, and mislocalization or absence of DNAH9. In addition, CLXN was undetectable in ciliary axonemes of individuals with defects in the ODA-docking machinery: ODAD1, ODAD2, ODAD3, and ODAD4. Furthermore, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility.
CONCLUSION
Our results revealed that pathogenic variants in CLXN cause PCD with defects in the assembly of distal ODAs in the respiratory cilia. CLXN should be referred to as ODA-docking complex-associated protein ODAD5.
Topics: Humans; Animals; Mice; Cilia; Kartagener Syndrome; Calcium-Binding Proteins; Axoneme; Mutation; Axonemal Dyneins
PubMed: 36727596
DOI: 10.1016/j.gim.2023.100798 -
Thorax Aug 2007A nationally funded diagnostic service should lead to improved outcome
A nationally funded diagnostic service should lead to improved outcome
Topics: Diagnostic Services; Early Diagnosis; Humans; Kartagener Syndrome; United Kingdom
PubMed: 17687094
DOI: 10.1136/thx.2007.083147 -
American Journal of Respiratory Cell... Oct 2019
Topics: Cilia; Dyneins; Humans; Kartagener Syndrome; Mutation
PubMed: 30951371
DOI: 10.1165/rcmb.2019-0103ED -
Transplant International : Official... 2023Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory...
Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.
Topics: Humans; Kartagener Syndrome; Retrospective Studies; Lung Transplantation; Biopsy; Data Collection
PubMed: 36865666
DOI: 10.3389/ti.2023.10819 -
European Journal of Pediatrics Aug 2022Primary ciliary dyskinesia (PCD) impairs pulmonary function, respiratory and peripheral muscle strength, and exercise capacity. We aimed to investigate the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
Primary ciliary dyskinesia (PCD) impairs pulmonary function, respiratory and peripheral muscle strength, and exercise capacity. We aimed to investigate the effects of active video games (AVGs) on pulmonary function, respiratory and peripheral muscle strength, exercise capacity, muscle oxygenation (SMO), physical activity, activities of daily living (ADL), and quality of life (QOL) in PCD. Thirty-two PCD patients were randomly assigned to AVG group (n = 16) and the control group (n = 16). AVG group underwent AVGs using Xbox-Kinect-360 device for 40 min/day, 3 days/week for 8 weeks plus airway clearance techniques (ACT), and the control group was applied ACT only. Pulmonary function, respiratory and quadriceps muscle strength, exercise capacity (6-min walk test [6MWT], incremental shuttle walk test [ISWT]), and ADL (Glittre ADL test) were assessed. SMO during ISWT and ADL test was also recorded. Physical activity and QOL (PCD-QOL) were evaluated. Pulmonary function; respiratory and quadriceps muscle strength; 6MWT and ISWT distance; physical activity; ADL performance; SMO; physical, emotional, and social functioning; treatment burden; and upper and lower symptom parameters of PCD-QOL significantly improved after 8 weeks in the AVG group (p < 0.05). There were no significant differences in measured parameters except emotional function and upper respiratory symptom scores of PCD-QOL in the control group (p > 0.05). Conclusion: The AVGs positively affect pulmonary (pulmonary function, respiratory muscle strength) and extrapulmonary (peripheral muscle strength, exercise capacity, SMO, physical activity, ADL, and QOL) characteristics in children with PCD. The AVGs may be added to the pulmonary rehabilitation program as an exercise training modality in patients with PCD. Trial registration: This study registered at ClinicalTrials.gov with NCT03832491 on February 6, 2019. What is Known: • It is indicated that exercise capacity is increased with traditional exercise-training in a case report of Kartagener Syndrome. What is New: • No randomized controlled study investigated the effects of exercise-training in PCD. • 8-week moderate-intensity active video gaming (AVGs) improves pulmonary and extrapulmonary features in children with PCD. AVGs may be preferable due to being enjoyable, providing visual and audial feedback in the pulmonary rehabilitation programs of PCD.
Topics: Activities of Daily Living; Child; Exergaming; Humans; Kartagener Syndrome; Muscle Strength; Quality of Life; Video Games
PubMed: 35536410
DOI: 10.1007/s00431-022-04490-z