Freeze fracture study of airway epithelium from patients with primary ciliary dyskinesia

BACKGROUND: The airway cilia of patients with primary ciliary dyskinesia (PCD) exhibit several anomalies when studied by transmission electron microscopy, but little is known about the ultrastructural organisation of ciliary membranes in these patients. Freeze fracture replication of airway epithelium from patients with PCD provides a means of achieving high resolution views of cell membrane structure. Ciliary necklaces are a specialised structural feature of ciliary membranes thought to serve as a timing mechanism for ciliary beat, and their characterisation in the cilia of patients with PCD may contribute new insights into the pathophysiology of this syndrome. METHODS: The nasal epithelium of three patients with PCD was freeze fractured and replicated with platinum and carbon shadowing. The resultant preparations were examined by transmission electron microscopy and the ciliary necklaces were compared with similar preparations of nasal biopsy specimens from normal healthy subjects. RESULTS: The ciliary necklaces of the three patients with PCD were normal with no overt differences from those of healthy individuals. CONCLUSIONS: The defective ciliary motility observed in patients with PCD does not appear to result from membrane dysfunction associated with overt disorganisation of ciliary necklace structure.     

Fertility in men with primary ciliary dyskinesia presenting with respiratory infection.

BACKGROUND--Primary ciliary dyskinesia is characterised by chronic rhinosinusitis, chronic bronchial sepsis (usually with bronchiectasis), dextrocardia in approximately 50% of cases, and male infertility. The latter, described in patients attending infertility clinics, results from immotile but viable spermatozoa. Experience in a respiratory clinic suggests that infertility in men is not invariable. METHODS--The seminal fluid of 12 men with primary ciliary dyskinesia, six with dextrocardia, who presented consecutively with upper and lower respiratory tract sepsis was examined. Nasal ciliary beating was dyskinetic or absent in all cases, and nasal ciliary ultrastructure was abnormal in those 11 patients examined. RESULTS--Viable but immotile spermatozoa with abnormal tail ultrastructure were found in the ejaculate of only two patients. Two other patients had apparently fathered children; seminology in both these cases showed a normal spermatozoa count, one with normal spermatozoal motility and normal ultrastructure, the other with moderately reduced spermatozoal motility and abnormal ultrastructure (dynein arm deficiency on the peripheral microtubule doublets). A further two patients had normal spermatozoa counts, normal spermatozoa tail ultrastructure, and normal or only moderately reduced motility of spermatozoa. The spermatozoa of one patient were normally motile but there was severe oligozoospermia, and five patients were azoospermic. CONCLUSIONS--Not all men with primary ciliary dyskinesia have immotile spermatozoa. Seminal analysis is recommended in men with primary ciliary dyskinesia so that accurate counselling about reproductive capability may be given.     

Living-donor lobar lung transplantation for primary ciliary dyskinesia

A ventilator-dependent patient with primary ciliary dyskinesia underwent successful living-donor lobar lung transplantation. The case was a 24-year-old woman who had developed recurrent lower respiratory infection and became ventilator-dependent due to severe bronchiectasis. Transmission electron microscopy of the resected bronchus demonstrated inner dynein arm deficiency.     

Cystic fibrosis, primary ciliary dyskinesia and non-cystic fibrosis bronchiectasis: update 2008-11

A review is presented of key clinical papers published in Thorax and elsewhere between 2008 and April 2011 which have advanced our understanding of cystic fibrosis (CF), primary ciliary dyskinesia and non-CF bronchiectasis. Studies were identified through searches of the Thorax archive and the Medline database. Within the field of CF, the following key themes were studied: diagnosis in equivocal CF, assessment of CF lung disease, novel therapies addressing the basic defect in CF, maintenance pulmonary therapies, management of early Pseudomonas infection, the microbiology of CF lung disease, renal impairment in CF and controversies in lung transplantation in CF.     

Ciliary disorientation: a possible variant of primary ciliary dyskinesia.

Random ciliary orientation has recently been proposed as a variant of primary ciliary dyskinesia. We report a 12 year old boy with all the features of primary ciliary dyskinesia and absent nasal mucociliary clearance in whom repeated biopsies of the nasal epithelium showed normal ciliary beat frequency. The only abnormality discovered was disorientation of the central microtubules of his cilia.     

A report of pregnancy following ICSI in one of two sisters with familiar primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a disorder of structure and function of motor ciliary and dyskinetic activity of ciliary in the fallopian tubes of affected women and could lead to infertility in some cases. In vitro fertilisation (IVF) is a choice of treatment in infertile women with PCD, which could conquer the tubal dysfunction. In this case study, we report a PCD affected woman with infertility who was treated by IVF and pregnancy was achieved but it failed due to the spontaneous abortion. We also performed whole-exome sequencing for this case and her PCD-affected sister, which did not reveal any genetic abnormality related to the PCD or infertility.     

Exhaled molecular profiles in the assessment of cystic fibrosis and primary ciliary dyskinesia

BackgroundEarly diagnosis and monitoring of disease activity are essential in cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). We aimed to establish exhaled molecular profiles as the first step in assessing the potential of breath analysis.MethodsExhaled breath was analyzed by electronic nose in 25 children with CF, 25 with PCD and 23 controls. Principle component reduction and canonical discriminant analysis were used to construct internally cross-validated ROC curves.ResultsCF and PCD patients had significantly different breath profiles when compared to healthy controls (CF: sensitivity 84%, specificity 65%; PCD: sensitivity 88%, specificity 52%) and from each other (sensitivity 84%, specificity 60%). Patients with and without exacerbations had significantly different breath profiles (CF: sensitivity 89%, specificity 56%; PCD: sensitivity 100%, specificity 90%).ConclusionExhaled molecular profiles significantly differ between patients with CF, PCD and controls. The eNose may have potential in disease monitoring based on the influence of exacerbations on the VOC-profile.     

Implementation of a gene panel for genetic diagnosis of primary ciliary dyskinesia

IntroductionPrimary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients.MethodsThis was a multicenter cross-sectional study of patients with a high suspicion of PCD according to European Respiratory Society criteria. We designed a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD.ResultsWe included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature.ConclusionsThe design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches.     

Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia

BACKGROUND: Primary ciliary dyskinesia (PCD) is associated with chronic airway inflammation resulting in bronchiectasis. METHODS: The levels of exhaled nitric oxide (eNO), carbon monoxide (eCO) and nasal NO (nNO) from bronchiectatic patients with PCD (n=14) were compared with those from patients with non-PCD bronchiectasis without (n=31) and with cystic fibrosis (CF) (n=20) and from normal subjects (n=37) to assess the clinical usefulness of these measurements in discriminating between PCD and other causes of bronchiectasis. RESULTS: Exhaled NO levels were lower in patients with PCD than in patients with non-PCD non-CF bronchiectasis or healthy subjects (median (range) 2.1 (1.3-3.5) ppb v 8.7 (4.5-26.0) ppb, p<0.001; 6.7 (2.6-11.9) ppb, p<0.001, respectively) but not lower than bronchiectatic patients with CF (3.0 (1.5-7.5) ppb, p>0.05). Nasal levels of nNO were significantly lower in PCD patients than in any other subjects (PCD: 54.5 (5.0-269) ppb, non-PCD bronchiectasis without CF: 680 (310-1000) ppb, non-PCD bronchiectasis with CF: 343 (30-997) ppb, control: 663 (322-1343) ppb). In contrast, eCO levels were higher in all patient groups than in control subjects (PCD: 4.5 (3.0-24.0) ppm, p<0.01, other bronchiectasis without CF: 5.0 (3.0-15.0) ppm, p<0.001; CF: 5.3 (2.0-23.0) ppm, p<0.001 v 3.0 (0.5-5.0) ppm). Low values in both eNO and nNO readings (<2.4 ppb and <187 ppb, respectively) identified PCD patients from other bronchiectatic patients with a specificity of 98% and a positive predictive value of 92%. CONCLUSION: The simultaneous measurement of eNO and nNO is a useful screening tool for PCD.     

1例原发性纤毛运动障碍伴阿斯匹林三联征患者行鼻内镜手术的护理

对1例原发性纤毛运动障碍伴阿斯匹林三联征患者行鼻内镜手术,手术顺利,术后无并发症。提出针对患者的疾病特征和护理需求,对患者及时实施心理干预、症状护理、并发症观察、健康教育等措施,可使患者平稳渡过围术期。     

Acute hypoxemia in a parturient with primary ciliary dyskinesia following the administration of intravenous oxytocin: a case report

Purpose

We present the case of a parturient diagnosed with primary ciliary dyskinesia with secondary bronchiectasis who developed significant hypoxemia following administration of intravenous oxytocin during Cesarean delivery under spinal anesthesia. This case suggests that oxytocin can affect pulmonary vascular tone and interfere with the protective effects of hypoxic vasoconstriction.

Clinical features

A 35-yr-old primigravida at 37 weeks gestation presented for a scheduled Cesarean delivery due to breech positioning and fetal abnormalities. The patient had a diagnosis of primary ciliary dyskinesia and had undergone a right middle lobectomy seven years earlier for resultant bronchiectasis. Pulmonary function testing in the month prior to delivery showed a 4% decline in her baseline FEV₁ to 1.06 L (32% of predicted value) but she was functionally well. The patient initially had an uneventful spinal anesthetic and maintained an oxygen saturation of 97% on room air in the supine position until delivery of her baby. An intravenous infusion of oxytocin for uterine contraction was started following removal of the placenta. The patient then became acutely hypoxemic with a drop in room air saturation to 84% but with no other accompanying hemodynamic instability. Maternal oxygen saturation did not improve with the addition of supplemental oxygen, and the patient had a significant arterial-alveolar oxygen gradient suggesting an intrapulmonary shunt. No supporting clinical, radiologic, or laboratory evidence of a thrombotic, air, or amniotic fluid embolism or mucous plug was detected. The patient remained hypoxemic during the postoperative period with gradual improvement back to baseline saturation in approximately 48 hr.

Conclusion

The vasodilatory effects of intravenous oxytocin on the pulmonary vasculature may worsen shunting and interfere with hypoxic pulmonary vasoconstriction, producing clinically significant hypoxemia in patients with comorbid lung disease. Oxytocin should be used with caution in patients with compromised lung function.     

Mucociliary transport using 99mTc-albumin colloid: a reliable screening test for primary ciliary dyskinesia

BACKGROUND: A study was undertaken to assess the reliability of the nasal mucociliary transport test using 99mTc-albumin colloid as a screening test for primary ciliary dyskinesia (PCD) and to compare it with the gold standard nasal biopsy for study of ciliary motility and ultrastructure. METHODS: During a 4 year period both tests were performed in 55 children referred with persistent or recurrent respiratory tract infections. Their median age was 4 years (range 1 month to 15 years). RESULTS: The nasal biopsy results were as follows: PCD, n = 8; secondary ciliary dyskinesia (SCD), n = 19; normal, n = 28. The mucociliary transport test was abnormal in 29 patients (all 8 with PCD, 7/19 with SCD, and 14/28 with a normal biopsy). The sensitivity of the mucociliary transport test to diagnose PCD was therefore 100% (8/8) (95% exact confidence limits 63.06 to 100.00); the specificity was only 55% (26/47) (40.95 to 69.89). The negative predictive value was 100% (26/26) (86.77 to 100.00) and the positive predictive value was 28% (8/29) (12.37 to 47.24). CONCLUSION: Mucociliary transport is a non-invasive screening test that can be performed even in infants. The sensitivity of the test is high but its specificity is low. A normal test result excludes PCD.     

Primary ciliary dyskinesia in association with Marfan's syndrome. A case report

Marfan's syndrome and primary ciliary dyskinesia are both disease entities with specific criteria for diagnosis. Pulmonary manifestations of Marfan's syndrome, including bronchiectasis, are well documented, but the association with ciliary dyskinesia is unknown. A case in which criteria for both diagnoses were satisfied is discussed.     

Variability in ciliary beat frequency in normal subjects and in patients with bronchiectasis.

BACKGROUND--There is a wide variation in tracheobronchial clearance of inhaled aerosol in normal subjects and in patients with bronchiectasis, but little information is available on the variability in ciliary beat frequency (CBF). METHODS--The variability in CBF was measured in 10 nasal mucosal samples from each of 19 normal controls and 23 stable bronchiectatic subjects. RESULTS--The CBF varied at different mucosal sites in both normal subjects and bronchiectatic patients. Although the CBF of the fastest beating cilia was similar in both groups, the CBF of the slowest beating cilia was, on average, lower and showed greater within subject variation in bronchiectatic than in normal subjects. CONCLUSIONS--There is a wide variation in CBF in nasal mucosal samples and this is significantly wider in bronchiectatic subjects with some cilia beating slowly. This may be a consequence of chronic inflammation or infection.