Aortic arch replacement with simultaneous antegrade cerebral and systemic perfusion using a single centrifugal pump driven 'split arterial line' extracorporeal circuit design.

The ability to provide antegrade cerebral and systemic perfusion simultaneously may negate the requirement for any prolonged period of circulatory arrest during complex aortic arch reconstruction procedures, depending on the cannulation strategy. We describe the development and successful implementation of a custom 'split arterial line' extracorporeal circuit configuration to facilitate complex aortic surgery. This circuit design offers a wide range of cannulation and perfusion strategies, is safe, adaptable, simple to manage, and avoids the use of roller pumps for blood delivery, which are associated with deleterious haematological complications during prolonged cardiopulmonary bypass cases. The split arterial line approach has now become the standardised methodology for facilitating complex aortic surgery at our institution.

Pollen season trends as markers of climate change impact: Betula, Quercus and Poaceae.

The incidences of respiratory allergies are at an all-time high. Pollen aeroallergens can reflect changing climate, with recent studies in Europe showing some, but not all, pollen types are increasing in severity, season duration and experiencing an earlier onset. This study aimed to identify pollen trends in the UK over the last twenty-six years for a range of pollen sites, with a focus on the key pollen types of Poaceae (grass), Betula (birch) and Quercus (oak) and to examine the relationship of these trends with meteorological factors. Betula pollen seasons show no significant trends for onset, first high day or duration but increasing pollen production in the Midlands region of the UK is being driven by warmer temperatures in the previous June and July. Quercus pollen seasons are starting earlier, due to increasing temperature and sunshine totals in April, but are not becoming more severe. The seasons are lasting longer, although no significant climate drivers for this were identified. The first high day of the Poaceae pollen season is occurring earlier in central UK regions due to an increasing trend for all temperature variables in the previous December, January, April, May and June. Severity and duration of the season show no significant trends and are spatially and temporally variable. Important changes are occurring in the UK pollen seasons that will impact on the health of respiratory allergy sufferers, with more severe Betula pollen seasons and longer Quercus pollen seasons. Most of the changes identified were caused by climate drivers of increasing temperature and sunshine total. However, Poaceae pollen seasons are neither becoming more severe nor longer. The reasons for this included a lack of change in some monthly meteorological variables, or land-use change, such as grassland being replaced by urban areas or woodland.

Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe.

Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season.

Fungal bronchitis is a distinct clinical entity which is responsive to antifungal therapy.

Chronic productive cough in the context of exacerbations of airway disease can be associated with positive sputum cultures for fungi, in particular Aspergillus fumigatus and Candida spp., suggesting fungal bronchitis, a condition not widely recognised, as a possible cause for the exacerbation. Our objective was to determine the response to antifungal therapy in patients with suspected fungal bronchitis. Retrospective analysis of data extracted from case records of patients under secondary care respiratory clinics who had been treated with triazole therapy for suspected fungal bronchitis between 2010-2017. Primary outcome was lung function response after 1 month of treatment. Nineteen patients with fungal bronchitis due to A. fumigatus and 12 patients due to Candida spp., were included in the study. Most of the patients, particularly in the Aspergillus group, had allergic fungal airway disease on a background of asthma. All but one of the patients in each group were recorded as showing clinical improvement with antifungal therapy. In the majority of patients this was reflected in an improvement in lung function. Aspergillus group: FEV1 (1.44 ± 0.8 L vs 1.6 ± 0.8 L: p < 0.02), FVC (2.49 ± 1.08 L vs 2.8 ± 1.1 L: p = 0.01), and PEF (260 ± 150L/min vs 297 ± 194ml/min: p < 0.02). Candida group: FEV1 (1.6 ± 0.76 L vs 2.0 ± 0.72 L: p < 0.004), FVC (2.69 ± 0.91 L vs 3.13 ± 0.7 L: p = 0.05), and PEF (271± 139L/min vs 333 ± 156 L/min: p = 0.01). Side effects of treatment were common, but resolved on stopping treatment. This service improvement project supports the idea that fungal bronchitis is a distinct clinical entity which is responsive to treatment. Controlled clinical trials to confirm the clinical impression that this is relatively common and treatable complication of complex airway disease are required.

Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively.

BACKGROUND: Sensitization to thermotolerant fungi, including filamentous fungi and Candida albicans, is associated with poor lung function in adults with severe asthma. Data in children are lacking. Environmental exposure to fungi is linked with acute severe asthma attacks, but there are few studies reporting the presence of fungi in the airways during asthma attacks. METHODS: We investigated the association between fungal sensitization and/or positive fungal sputum culture and markers of asthma severity in children with chronic and acute asthma. Sensitization was determined using serum-specific IgE and skin prick testing against a panel of five fungi. Fungal culture was focused towards detection of filamentous fungi from sputum samples. RESULTS: We obtained sensitization data and/or sputum from 175 children: 99 with chronic asthma, 39 with acute asthma and 37 controls. 34.1% of children with chronic asthma were sensitized to thermotolerant fungi compared with no children without asthma (p =< 0.001). These children had worse pre-bronchodilator lung function compared with asthmatics without sensitization including a lower FEV1 /FVC ratio (p < .05). The isolation rate of filamentous fungi from sputum was higher in children with acute compared with chronic asthma. CONCLUSIONS: Fungal sensitization is a feature of children with chronic asthma. Children sensitized to thermotolerant fungi have worse lung function, require more courses of systemic corticosteroids and have greater limitation of activities due to asthma. Asthma attacks in children were associated with the presence of filamentous fungi positive sputum culture. Mechanistic studies are required to establish whether fungi contribute directly to the development of acute asthma.

The airway fungal microbiome in asthma.

BACKGROUND: Fungal involvement in asthma is associated with severe disease. The full spectrum of fungal species in asthma is not well described and is derived largely from insensitive culture techniques. OBJECTIVES: To use high-throughput sequencing to describe the airway mycobiota in asthmatics with and without fungal sensitization and healthy controls; to compare samples representing different airway compartments; to determine whether the mycobiota was influenced by the fungal composition of outdoor air; and to compare findings with clinically relevant outcomes. METHODS: We amplified the internal transcribed spacer region 2 of the nuclear ribosomal operon to identify the fungal species present. Ninety-seven subjects were recruited and provided sputum (83 asthmatics; 14 healthy subjects), with 29 also undergoing a bronchoscopy. A subset of airway samples were compared with matched outdoor air and mouthwash samples. RESULTS: Two hundred and six taxa at the species level were identified in sputum, most at low relative abundance. Aspergillus fumigatus, Candida albicans and Mycosphaerella tassiana had the highest relative abundances and were the most prevalent species across all subjects. The airway mycobiota consisted of a complex community with high diversity between individuals. Notable shifts in the balance of fungi detected in the lung were associated with asthma status, asthma duration and biomarkers of inflammation. Aspergillus tubingensis, a member of the Aspergillus niger species complex, was most prevalent from bronchoscopic protected brush samples and significantly associated with a low sputum neutrophilia. Cryptococcus pseudolongus, from the Cryptococcus humicola species complex, was more abundant from bronchoscopy samples than sputum, and differentially more abundant in asthma than health. CONCLUSIONS AND CLINICAL RELEVANCE: The airway mycobiota was dominated by a relatively small number of species, but was distinct from the oropharyngeal mycobiota and air samples. Members of the A. niger and C. humicola species complexes may play unexpected roles in the pathogenesis of asthma.

HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants.

Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 × 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.