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Nasal nitric oxide is an important test in the diagnostic pathway for primary ciliary dyskinesia.
No full textDiffuse bronchiectasis of genetic or idiopathic origin
No full textBronchiectasis is a significant cause of morbidity and mortality. It is the end point of a pathological process. We should be aiming to identify at risk patients before they develop bronchiectasis and to treat them aggressively to prevent disease progression. With improved social conditions and health care, infective causes of bronchiectasis have diminished in higher-income countries, and genetic causes are therefore relatively more common. The underlying cause of bronchiectasis should always be sought and readdressed, for example as discoveries of innate immune defects are made. ‘Idiopathic bronchiectasis’ should be a diagnosis of last resort. This chapter reviews potential genetic causes of bronchiectasis and suggests a plan for investigating the underlying aetiology. Management is discussed but it is important to note that suggested treatment strategies are often extrapolated from evidence in bronchiectasis associated with cystic fibrosis; this is likely to be inappropriate in diseases of differing pathophysiology. Rare lung diseases need to be moved out of the ‘orphan’ category by instigating multi-centre, multi-national clinical trials and producing disease-specific evidence-based guidelines
Monovalent inactivated split-virion AS03-adjuvanted pandemic influenza A (H1N1) vaccine
No full textThe first cases of pandemic influenza A (H1N1) 2009 infection were seen in Mexico in March 2009. Since then, it is thought to have been responsible for at least 18,337 deaths globally. Owing to the young age of fatalities, there have been an estimated 2 million years of life lost, which is comparable to the previous pandemics of 1957 and 1968. In this article, we consider the available data on a monovalent inactivated split-virion AS03-adjuvanted pandemic influenza A (H1N1) vaccine, Pandemrix™ (GlaxoSmithKline, Rixensart, Belgium). At present, Pandemrix appears to be highly immunogenic in all age groups, including children and infants under 3 years of age, with an acceptable safety profile in the context of an influenza pandemic. However, owing to the novel adjuvant, further studies on the safety, immunogenicity and vaccine effectiveness of Pandemrix together with robust post-marketing surveillance are required
Neuronal NOS localises to human airway cilia
No full textWe report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function
Nitric oxide in primary ciliary dyskinesia.
No full textNitric oxide is continually synthesized in the respiratory epithelium and is upregulated in response to infection or inflammation. Primary ciliary dyskinesia is characterized by recurrent sinopulmonary infections due to impaired mucociliary clearance. Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition. These low levels were first described over 15 years ago but the underlying mechanisms have yet to be fully elucidated. We review epithelial nitric oxide synthesis, release and measurement in the upper airways with particular reference to primary ciliary dyskinesia. The key hypotheses that have been proposed to explain the low levels in this condition are explored and the potential benefits of augmenting airway nitric oxide levels are considered. Further work in these patients clarifying both whether the respiratory epithelium is able to biosynthesise normal levels of nitric oxide and the role played by abnormalities in the anatomy of the paranasal sinuses is essential. While nitric oxide augmentation is unlikely to be beneficial in common primary ciliary dyskinesia phenotypes, it has potential in the treatment of secondary dyskinesias and may also improve treatment of bacterial infections, particularly where biofilms are implicated
PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia
Full text linkSymptoms of primary ciliary dyskinesia (PCD) are nonspecific and guidance on whom to refer for testing is limited. Diagnostic tests for PCD are highly specialised, requiring expensive equipment and experienced PCD scientists. This study aims to develop a practical clinical diagnostic tool to identify patients requiring testing.Patients consecutively referred for testing were studied. Information readily obtained from patient history was correlated with diagnostic outcome. Using logistic regression, the predictive performance of the best model was tested by receiver operating characteristic curve analyses. The model was simplified into a practical tool (PICADAR) and externally validated in a second diagnostic centre.Of 641 referrals with a definitive diagnostic outcome, 75 (12%) were positive. PICADAR applies to patients with persistent wet cough and has seven predictive parameters: full-term gestation, neonatal chest symptoms, neonatal intensive care admittance, chronic rhinitis, ear symptoms, situs inversus and congenital cardiac defect. Sensitivity and specificity of the tool were 0.90 and 0.75 for a cut-off score of 5 points. Area under the curve for the internally and externally validated tool was 0.91 and 0.87, respectively.PICADAR represents a simple diagnostic clinical prediction rule with good accuracy and validity, ready for testing in respiratory centres referring to PCD centres
Overcoming challenges in the management of primary ciliary dyskinesia: the UK model
No full textPrimary 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
Accuracy of diagnostic testing in primary ciliary dyskinesia
Full text linkDiagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30?nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (?30?nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ?10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority
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