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Publications (82)
Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10-15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT)...
Post-acute COVID-19 causes long term sequalae in adults. This is less well described in children. We performed clinical assessments on a large cohort of children and young people admitted with a positive SARS-CoV-2 RNA swab. We assessed for symptoms of post-acute COVID-19 syndrome after 4 weeks or more. We found that most (85%) of children made a f...
Exposure to tobacco smoke is harmful to children and young people (CYP). There is, to our knowledge, no published evidence quantifying the success of smoking cessation interventions targeted at both CYP and their parents or guardians in paediatric respiratory clinics. We offered 102 participants smoking cessation advice, using motivational intervie...
Post-acute COVID-19 causes long term sequalae in adults. This is less well described in children. We performed clinical assessments on a large cohort of children and young people admitted with a positive SARS-CoV-2 RNA swab. We assessed for symptoms of post-acute COVID-19 syndrome after 4 weeks or more. We found that most (85%) of children made a f...
Tonsillectomy and adenoidectomy (T&A) is frequently performed in children with sickle cell disease (SCD). Our aim was to evaluate the impact of this surgery on overnight oxygenation and rates of complications in these patients.
Children with SCD who underwent T&A between 2008 and 2014 in two tertiary hospitals were retrospectively evaluated. Overni...
This case alerts professionals to take a broad approach when considering childhood chronic cough in sickle cell disease. Certain respiratory conditions are difficult to recognise in childhood, with many children suffering from delayed diagnosis. https://bit.ly/2GZAgmE.
Objectives
To investigate the agreement between pulse oximetry (SpO 2 ) and oxygen saturation (SaO 2 ) measured by CO-oximetry on arterialised earlobe blood gas (EBG) in children and adolescents with sickle cell disease (SCD).
Design and setting
We retrospectively reviewed 39 simultaneous and paired SaO 2 EBG and SpO 2 measurements from 33 ambulat...
Introduction:
Lung clearance index (LCI) is a measure of airway disease that has been shown to be abnormal in asthma. We hypothesized that LCI would be higher (worse) in children with severe therapy-resistant asthma (STRA) compared with difficult asthma (DA) and healthy controls and that LCI would fall in response to parenteral steroids in STRA....
Introduction
Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and reduced life expectancy. Hydroxyurea (HU) has been shown to reduce the frequency and severity of vaso-occlusive episodes in SCD. Hypoxaemia and intermittent nocturnal oxygen desaturations occur frequently in ch...
Background:
Nutrition is closely related to mortality and pulmonary and respiratory muscle function in cystic fibrosis (CF) patients. We initially validated results from a bioelectrical impedance device against dual energy x-ray absorptiometry (DEXA). We then determined whether fat free mass assessed by a portable impedance device rather than body...
Introduction
Many factors might influence length of chest drainage (LOCD) when managing parapneumonic effusions/empyema including effusion size, septations, extent of pneumonia, presence of air leaks, pathogen virulence, fibrinolytic therapy with urokinase and local policies. UK guidelines recommend using the same fixed volumes for infants and for...
Introduction
Severe therapy resistant asthma (STRA) in children is heterogeneous: many have normal lung function, however there is a group with persistent airflow limitation (PAL). Little is known about PAL in children and previous studies are limited by the definitions used. We hypothesised that when PAL is classified according to stringent criter...
Introduction
Children with severe therapy resistant asthma (STRA) have heterogeneous disease with variable response to steroids. Currently, spirometry (forced expiratory volume in 1 s (FEV1)) is most widely used to assess treatment response. We hypothesised lung clearance index (LCI) would more sensitively assess steroid response than FEV1 alone, u...
Conclusions:
This review highlights that the currently available evidence does not support the use of montelukast in preschool children with recurrent wheeze. We recommend further studies to investigate if a 'montelukast responder' phenotype exists, and how these can be easily identified in the clinical setting. What is Known: • Current guidelines...
Background
Sickle Cell Disease (SCD) affects about 1 in 1,900 children born in the UK. Respiratory morbidity affects children as well as adults with SCD and the burden may have been underestimated in the past. The published literature suggests that asthma, airway hyper-reactivity and sleep disordered breathing (SDB) are common in children with SCD....
Background:
Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in paediatric asthma is unknown.
Objectives:
To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA).
Me...
Evidence has shown that omalizumab is highly effective for the treatment of severe allergic asthma inadequately controlled on step 5 of BTS guideline.
OBJECTIVE: To evaluate the efficacy of Omalizumab in carefully selected group of children with severe allergic asthma aged 6 -18 years.
METHOD: This is a retrospective observational study of 19 child...
Introduction: Pseudomonas aeruginosa (PA) is associated with worsening morbidity and mortality in children with long term O2, long term ventilation or tracheostomy. There are currently no guidelines for management of PA in these patients.
Aim: To report on incidence and management of PA infection in children with long term O2, long term ventilation...
Background: Evidence suggests poor agreement between pulse oximetry SpO2 and arterial blood gas (ABG) SaO2 in measuring Hb O2 saturation in sickle cell disease (SCD) (Blaisdell, Arch Pediatr Adoles Med 2000). Earlobe blood gas co-oximetry (EBG) is an easily performed painless method of measuring SaO2, with good agreement with ABG (Zavorsky, Respir...
Background Wheeze in the preschool age has a high prevalence and healthcare burden. There is conflicting evidence of the effectiveness of montelukast, a leukotriene receptor antagonist, in preschool wheeze. Recent meta-analyses have focused on its use in viral induced or multiple-trigger wheeze, however such groups are unlikely to exist in real-lif...
Background:
There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients.
Objective:
We sought to evaluate the utility of a multidomain approach incorporating sympto...
Background:
Ethnicity may influence response to treatment of asthmatic patients, but this is controversial. This study's objective is to determine if ethnicity influences the response to intramuscular steroid (eliminating adherence as an issue).
Methods:
Children with severe therapy resistant asthma who had previously undergone a detailed assess...
The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored.
We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33.
Eighty-two children (median age,...
Rhinovirus infections are the dominant cause of asthma exacerbations, and deficient virus induction of IFN-α/β/λ in asthmatic patients is important in asthma exacerbation pathogenesis. Mechanisms causing this interferon deficiency in asthmatic patients are unknown.
We sought to investigate the expression of suppressor of cytokine signaling (SOCS) 1...
Introduction Therapeutic options for children with severe asthma are limited. Clinical studies support the use of the anti-IgE antibody, omalizumab, in children with severe atopic asthma. However, children included in these studies had less severe disease than those in whom omalizumab is currently recommended. Little is known about the clinical eff...
Parental smoking is known to worsen asthma symptoms in children and make them refractory to asthma treatment, but the molecular mechanism is unclear. Recently, oxidative stress from tobacco smoke has been reported to impair histone deacetylase-2 (HDAC2) via phosphoinositide-3-kinase (PI3K)/Akt activation and thus to reduce corticosteroid sensitivit...
Children with severe asthma have recurrent exacerbations and/or persistent symptoms despite maximal treatment with conventional medication. Severe asthma in childhood is particularly difficult to treat, with substantial morbidity. There are few randomised controlled trials in these patients; evidence therefore has to be extrapolated from adult stud...
Background:
TH2 cytokines are not responsible for the ongoing symptoms and pathology in children with severe therapy-resistant asthma (STRA). IL-33 induces airway hyperresponsiveness, but its role in airway remodeling and steroid resistance is unknown.
Objective:
We sought to investigate the relationship between IL-33 and airway remodeling in pe...
The inflammatory phenotypes of severe asthma in adults may be reflected in peripheral blood. If this were true in children with severe therapy-resistant asthma (STRA), invasive tests could be avoided. At the moment there is no conclusive evidence in children.
All patients underwent blood tests, exhaled nitric oxide (FeNO), sputum induction, broncho...
Deficient type I interferon-β and type III interferon-λ induction by rhinoviruses has previously been reported in mild/moderate atopic asthmatic adults. No studies have yet investigated if this occurs in severe therapy resistant asthma (STRA). Here, we show that compared with non-allergic healthy control children, bronchial epithelial cells culture...
Background:
Increased airway smooth muscle (ASM) is a feature of established asthma in schoolchildren, but nothing is known about ASM in preschool wheezers.
Objective:
We sought to determine endobronchial biopsy specimen ASM area fraction in preschool wheezers and its association with asthma at school age.
Methods:
ASM area, reticular basement...
BACKGROUND: Rhinovirus (RV)-induced pulmonary exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium in vitro. Here, we assess in vivo the association of RV prevalence and load with antiviral defense mechanisms, airway inflammation, and lung function parameters in children...
Background Children with problematic severe asthma (PA) may have genuine therapy-resistant disease, or may be difficult-to-treat because of unaddressed potentially modifiable factors.
Objectives Evaluate the long-term efficacy of a structured protocol including a nurse-led assessment1 (Stage 1) in identifying modifiable factors and differentiating...
The pathology of pediatric severe therapy-resistant asthma (STRA) is little understood.
We hypothesized that STRA in children is characterized by airway eosinophilia and mast cell inflammation and is driven by the T(H)2 cytokines IL-4, IL-5, and IL-13.
Sixty-nine children (mean age, 11.8 years; interquartile range, 5.6-17.3 years; patients with STR...
Introduction Spirometry is often normal in children with STRA, and is thus a poor outcome measure (1). Lung Clearance Index is a sensitive, non-effort dependent measure of distal airway gas mixing, which has been shown to be more sensitive than spirometry in Cystic Fibrosis (2). We hypothesised that LCI would be a better marker of steroid response...
Introduction
Severe asthma with fungal sensitisation (SAFS) in adults is associated with reduced lung function and increased morbidity [EurRespir J 2006;
27
:615?26, Am J RespirCare Med 2009;
179
:11?18]. We hypothesised that fungal sensitisation in children with severe, therapy-resistant asthma (STRA) is associated with increased symptoms, medic...
Background A small proportion of patients with long standing severe asthma develop irreversible airway obstruction (persistent airflow limitation (PAL)). There is no agreed definition of PAL in children, but pragmatically, most would define it as post steroid, post-bronchodilator FEV1 percent predicted <80% or Z score less than −1.96, with normativ...
During air flight, cabin pressurisation produces an effective fraction of inspired oxygen (FiO(2)) of 0.15. This can cause hypoxia in predisposed individuals, including infants with bronchopulmonary dysplasia (BPD), but the effect on ex-preterm babies without BPD was uncertain. The consequences of feeding a baby during the hypoxia challenge were al...
Defining atopy in children with severe, therapy-resistant asthma is complex. There is currently no gold standard test; both skin prick testing (SPT) and allergen-specific IgE (sIgE) are used. Furthermore, atopy is increasingly considered to be a spectrum, not an all-or-none phenomenon.
SPTs and sIgE cannot be used interchangeably, and if both tests...
Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion.
We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of...
Background In asthma there is a direct relationship between tissue eosinophilic inflammation and RBM thickness. However, relationships between components of remodelling have not been explored, but may be important especially in determining disease severity. There are no reports of an association between smooth muscle mass and asthma severity in chi...
Background Studies of airway inflammation and remodelling may help us to understand the pathophysiology of SA. Adult studies have shown mast cell inflammation within smooth muscle is specific to asthma and is associated with airway hyperresponsiveness (AHR). However, this has not been studied in childhood disease.
Hypothesis Children with SA have i...
Dysfunctional swallowing is an uncommon, but important cause of bronchiectasis. We describe a child with a brainstem tumor, who developed bronchiectasis caused by chronic aspiration secondary to a dysfunctional swallow. The case highlights the importance of thorough and repeated evaluation before a diagnosis of idiopathic bronchiectasis is made. If...
A rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. We compared the airway microbiota at three levels in adult patients with asthma, the related condition of COPD, and controls. We also studied bronchial lavage from asthmatic children and controls.
We identified 5,054 16S rRN...
To evaluate and identify potentially modifiable factors in children with problematic asthma by a nurse-led assessment and home visit.
Observational cohort study.
A tertiary paediatric respiratory centre.
71 children, aged 4.5-17.5 years, with problematic asthma currently under follow-up at a tertiary respiratory centre.
A nurse-led hospital visit f...
Exciting new data are increasing the evidence base for the management of paediatric asthma. To inform the treatment of preschool wheeze, the best current classification is into episodic (viral) and multitrigger wheeze, rather than according to epidemiological pattern (transient versus persistent) and the presence or absence of atopy. Episodic (vira...
This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction ( F eNO ) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paedi...
During air flight, cabin pressurisation results in a reduced fraction of inspired oxygen to 0.15. Healthy children desaturate by around 4% and remain asymptomatic. However children under the age of 1 year are more susceptible to hypoxia, especially if they were born preterm, and even more so if they are survivors of chronic neonatal lung disease. P...
