Paroxysmal dyspnoea in asthma: Wheeze, ILO or dysfunctional breathing?

Paroxysms of dyspnoea in the general population are commonly reported and are frequently assumed to be asthma-related, especially if this diagnostic label has been previously applied. Often, this is not the case. Inducible Laryngeal Obstruction (ILO) and Dysfunctional Breathing (DB) are common comorbid conditions that go unrecognised in many difficult-to-treat asthmatics. On average, these patients have a delay in diagnosis of almost 5 years. This delay, along with ineffective, inappropriate escalation of asthma therapy, frequent hospital presentations for uncontrolled symptoms, and even intensive care admissions, magnifies patient morbidity and poor quality of life. ILO and DB have similar presentations and triggers to asthma. Differentiating between them can be challenging, especially in centres that do not have access to multidisciplinary subspecialty asthma services. Objectively confirming the diagnosis can likewise be challenging as symptoms fluctuate, and gold-standard investigations require extensive experience. This mini-review will summarise the clinical features of ILO and DB, with particular focus in the context of individuals treated for asthma. This narrative review will define each condition, highlight poignant aspects of the history and describe elements of the diagnostic pathway to gain objective confirmation.

Oxygen exchange and C-reactive protein predict safe discharge in patients with H1N1 influenza.

BACKGROUND: : Pandemic influenza has potential to overwhelm healthcare resources. There is uncertainty over performance of existing triage tools for hospital admission and discharge decisions. AIM: : Our aim was to identify clinical criteria that predict safe discharge from hospital and develop a pragmatic triage tool to guide physician decision-making. DESIGN: : We retrospectively examined an existing database of patients who presented to the Royal Liverpool University Hospital during the 2010-11 influenza pandemic. METHODS: Inclusion criteria: patients ≥18 years, with PCR confirmed H1N1 influenza. Exclusion criteria: died in the emergency department or case notes unavailable. Successful discharge was defined as discharge within 24 h of presentation and no readmission within 7 days. RESULTS: Eighty-six patients were included and 16 were successfully discharged. Estimated P/F ratio and C-reactive protein predicted safe discharge in a multivariable logistic regression model (AUC 0.883). A composite univariate predictor (estimated P/F minus C-reactive protein, AUC 0.877) was created to calculate specific cut off points for sensitivity and specificity. A pragmatic decision tool was created to incorporate these thresholds and relevant guidelines. Discharge: SpO 2 (in air) ≥ 94% and CRP <50. Observe: SpO 2 ≥ 94% and CRP >50 or SpO 2 ≤ 93% and CRP <50. Admit: SpO 2 ≤ 93% and CRP >50. CONCLUSIONS: We identified that oxygen exchange and CRP, a marker of acute inflammation, were the most important predictors of safe discharge. Our proposed simple triage model requires validation but has the potential to aid clinical decisions in the event of a future pandemic, and potentially for seasonal influenza.

Defining and managing risk in asthma.

Asthma attacks are a major global source of morbidity and cost. The incidence and impact of asthma attacks have not improved despite widespread adoption of effective universal treatment guidelines. Consequently, there is increasing interest in managing asthma based on specific assessments of both current symptoms and future risk. In this review, we consider 'risk' in asthma, and how it might be assessed from the patient's history and objective measurements. We also discuss the potential for encouraging shared decision-making and improving medical consensus through explicit communication of risk and highlight the potential opportunities and challenges in risk assessment to improve asthma management through individualised treatment strategies.

Can mobile technology improve response times of junior doctors to urgent out-of-hours calls? A prospective observational study.

BACKGROUND: The Hospital at Night system has been widely adopted to manage Out-of-Hours workload. However, it has the potential to introduce delays and corruption of information. The introduction of newer technologies to replace landlines, pagers and paper may ameliorate these issues. AIM: To establish if the introduction of a Hospital at Night system supported by a wireless taskflow system affected the escalation of high Early Warning Scores (EWSs) to medical attention, and the time taken to medical review. DESIGN: Prospective 'pre and post' observational study in a teaching hospital in the UK. METHODS: Review of observation charts and medical records, and data extraction from the electronic taskflow system. RESULTS: The implementation of a technology-supported Hospital at Night system was associated with a significant decrease in time to documentation of initial review in those who were reviewed. However, there was no change in the proportion of those with a high EWS that were reviewed, and throughout the study a majority of patients with high EWSs were not reviewed in accordance with guidelines. CONCLUSION: Introduction of a Hospital at Night system supported by mobile technology appeared to improve the transfer of information, but did not affect the nursing decision whether to escalate abnormal findings.

Genome-wide association study to identify genetic determinants of severe asthma.

BACKGROUND: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. OBJECTIVE: To identify common genetic variants affecting susceptibility to severe asthma. METHODS: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. RESULTS: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. CONCLUSIONS: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

What is severe asthma?

Asthma is common, and some individuals are severely affected by it. Learned institutions have sought to provide a definition of 'severe asthma' to facilitate research and clinical care. This is a challenging undertaking given the difficulty in defining asthma and the lack of supportive evidence for a distinct severe asthma phenotype. In this review, we discuss the rationale for a definition of severe asthma and the relative merits of the sequential attempts that have been made to produce such a definition. The difficulty in disentangling control and severity is highlighted, as is the heterogeneity of phenotype in severe asthma, and potential for misclassification. We conclude that the search for a singular definition of severe asthma is problematic, though likely to continue. We suggest the alternative strategy of using classifiers with a specific aim related to symptoms, pathophysiology or service provision.

Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort.

OBJECTIVE: The aim of this study was to estimate the contribution of polymorphisms in the positionally cloned asthma candidate genes ADAM33, PHF11, DPP10, GPRA and PTGDR to the risk of asthma, total and specific immunoglobulin E level, lung function and wheezing in a large, nationally representative, population. METHODS: An association analysis was undertaken using genotype data for tagging and previously associated single nucleotide polymorphisms (SNPs) in regions of these genes and longitudinal phenotype data from singletons of white ethnicity in the British 1958 Birth Cohort DNA archive (n = 7703). Population-attributable risk fractions for SNPs showing association were calculated. RESULTS: Polymorphisms producing small but statistically significant increases in asthma risk (OR 1.1 per allele) were identified in DPP10 and ADAM33, with the strongest evidence being for SNPs tagging the DPP10 gene. No individual SNP in any gene under study markedly increased risk for any of the phenotypes in the population studied. CONCLUSIONS: These data suggest that DPP10 and ADAM33 influence asthma risk in the UK population. However, the effects driven by any given locus are small, and genotyping of multiple polymorphisms in many genes will be needed to define a full genetic profile for disease risk.

Unintentional parathyroidectomy during thyroidectomy.

OBJECTIVES: In the United States thyroidectomy is a frequently performed surgery by both general and head and neck surgeons. Even the most experienced thyroid surgeon, however, has probably received a pathology report stating that an incidental parathyroid gland or parathyroid tissue was found in the submitted thyroidectomy specimen. The aim of this report is to explore some of the pathologic and clinical characteristics of unintentional parathyroidectomy during thyroidectomy. STUDY DESIGN: A retrospective review was performed of thyroidectomies performed at the University of California, Los Angeles, Center for the Health Sciences between 1989 and June 1998 which had pathology reports showing parathyroid tissue contained within the thyroidectomy specimen. This excluded any tissue submitted separately to be evaluated for parathyroid tissue and parathyroid tissue removed unintentionally during a thyroidectomy for a different procedure such as a laryngectomy or surgery for parathyroid disease. METHODS: The pathology slides were reviewed to determine the incidence of unintentional parathyroid tissue removal, the size of the parathyroid tissue found within the thyroid specimen, the location of the parathyroid tissue (extracapsular, intracapsular, intrathyroidal), and whether this unintentional parathyroidectomy during thyroidectomy caused clinical consequences. RESULTS: Four hundred fourteen applicable thyroidectomies were performed during this time with 45 (11%) discovered cases of unintentional parathyroidectomy during thyroidectomy. Twenty-five (56%) cases were discovered during thyroidectomy for benign disease, and 20 (44%) during thyroidectomy for malignant thyroid disease. All the parathyroid tissue was normal and was found in extracapsular (58%), intracapsular (20%), or intrathyroidal (22%) locations. Of these 45 cases, recurrent laryngeal nerve paralysis was found only in two patients who had the nerve resected intentionally during the thyroidectomy, and none of the patients developed permanent hypocalcemia. CONCLUSIONS: Incidental parathyroid gland tissue was reported in 11% of the thyroidectomies performed in our series, without the clinical consequence of hypocalcemia. The majority (78%) of this parathyroid tissue was found in the extracapsular and intracapsular locations; therefore it is possible that these parathyroid glands may be identified and preserved with more meticulous inspection of the thyroid capsule during and after thyroidectomy to decrease the incidence of unintentional parathyroidectomy during thyroidectomy in the future.