1,721,018 research outputs found
NO way!: Nasal nitric oxide measurement in infants
No full textPrimary ciliary dyskinesia (PCD) generally causes symptoms from the first weeks of life, but diagnosis is usually delayed for years or can be missed altogether. Referral for diagnostic testing is often late because key symptoms, such as wet cough, chronic rhinitis and recurrent upper and lower respiratory tract infection, are non-specific. An international survey of patients reported that 37% had >40 visits to medical professionals due to PCD-related symptoms before being referred for diagnostic testing [1]. Approximately 50% of children with PCD have situs inversus, a rare condition in the general population, and it is therefore not surprising that these patients are investigated earlier. A European survey found that age of diagnosis was at 3.5 years in those with situs inversus and 5.8 years in children with normal situs [2]. Assuming a prevalence of 1 in 10 000 [3], we expect ∼1180 diagnosed children in England (childhood population ∼11.8 million); however, there are currently only ∼340 children in the National Paediatric PCD Service. This highlights a huge proportion of undiagnosed patients even in a country with a national PCD service [4]. This is in stark contrast to cystic fibrosis (CF) where neonatal screening programmes ensure that diagnosis occurs in early infancy in many countries, with positive impact on clinical outcome [5]. Young children with PCD have similarly impaired forced expiratory volume in 1 s to children with CF [6], and require multidisciplinary treatment. Early diagnosis facilitates a management plan, including regular airway clearance physiotherapy, surveillance for airway pathogens with treatment of respiratory exacerbations, genetic counselling for families, audiology monitoring and management of conductive hearing loss [7, 8]. We expect that early diagnosis would delay respiratory decline and ensure specialist treatment of ear, hearing and nasal issues, thereby optimising health, psychological, social and educational outcomes.
There is no single gold standard test for PCD diagnosis. Presently, the diagnosis is made in patients with a compatible medical history following a demanding combination of tests including nasal nitric oxide (nNO), high-speed video microscopy, transmission electron microscopy, genetics, and culture of respiratory epithelial cells [7, 9–12]. These tests are costly and need experienced staff using sophisticated equipment, hence testing is restricted to reference centres which may be geographically distant from the patient. Identifying the correct patients for testing is therefore important and screening tools are needed. Although individual symptoms are non-specific, the pattern of symptoms is often characteristic. A typical history might include neonatal respiratory distress in an infant with no risk factors, a daily wet cough starting in early infancy, recurrent chest infections, persistent rhinitis and serous otitis media. Screening tools (e.g. PICADAR) to identify patients based on their clinical history are helpful but require a history that might not yet have evolved in young infants [13, 14]
Nasal nitric oxide is an important test in the diagnostic pathway for primary ciliary dyskinesia.
No full textManifesting carriage of a Duchenne muscular dystrophy mutation: An unusual cause of impaired lung function in CF
No full textNasal nitric oxide screening for primary ciliary dyskinesia: systematic review and meta-analysis
No full textNasal nitric oxide (nNO) concentrations are low in patients with primary ciliary dyskinesia (PCD) providing a noninvasive screening test. We conducted a systematic review of the literature to examine the utility of nNO in screening for PCD, in particular 1) different respiratory manoeuvres during sampling (velum closure, tidal breathing, etc.), 2) accuracy in screening young/uncooperative children, 3) stationary versus portable analysers, and 4) nNO in "atypical" PCD. 96 papers were assessed according to modified PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and 22 were included in this review. Meta-analysis of 11 studies comparing nNO during a velum closure breath hold gave a mean±sd nNO of 19.4±18.6 nL·min(-1) in PCD (n = 478) and 265.0±118.9 nL·min(-1) in healthy controls (n = 338). Weighted mean difference for PCD versus healthy controls was 231.1 nL·min(-1) (95% CI 193.3-268.9; n = 338) and 114.1 nL·min(-1) (95% CI 101.5-126.8; n = 415) for PCD versus cystic fibrosis. Five studies of nNO measurement during tidal breathing demonstrated that this is an acceptable manoeuvre in young children where velum closure is not possible, but the discriminatory value was reduced. Four small studies of portable NO analysers suggest these are reliable tools for screening for PCD. However, nNO must be interpreted alongside clinical suspicion. Future studies should focus on standardising sampling techniques and reporting
Diffuse 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
Genetic testing in the diagnosis of primary ciliary dyskinesia: state-of-the-art and future perspectives
No full textPrimary ciliary dyskinesia (PCD) is a heterogeneous autosomal recessive condition affecting around 1:15,000. In people with PCD, microscopic motile cilia do not move normally resulting in impaired clearance of mucus and debris leading to repeated sinopulmonary infection. If diagnosis is delayed, permanent bronchiectasis and deterioration of lung function occurs. Other complications associated with PCD include congenital heart disease, hearing impairment and infertility. A small number of longitudinal studies suggest that lung function deteriorates before diagnosis of PCD but may stabilise following diagnosis with subsequent specialist management. Early diagnosis is therefore essential, but for a number of reasons referral for diagnostic testing is often delayed until older childhood or even adulthood. Functional diagnostic tests for PCD are expensive, time consuming and require specialist equipment and scientists. In the last few years, there have been considerable developments to identify genes associated with PCD, currently enabling 65% of patients to be identified by bi-allelic mutations. The rapid identification of new genes continues. This review will consider the evidence that early diagnosis of PCD is beneficial. It will review the recent advances in identification of PCD-associated genes and will discuss the role of genetic testing in PCD. It will then consider whether screening for PCD antenatally or in the new born is likely to become a feasible and acceptable for this rare disease
Primary tracheomalacia and persistent wheezing in cystic fibrosis during infancy
No full textPersistent wheezing, poorly responsive to bronchodilator therapy, raises concerns about the progression of cystic fibrosis-related lung disease. We describe 3 infants with such symptoms who were observed to have primary tracheomalacia. The diagnoses were made using flexible bronchoscopy during spontaneous respiration. Early recognition of this etiology can limit unnecessary investigation and the overuse of empirical treatments such as oral and inhaled corticosteroids.</p
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