Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic PEEP in COPD?

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume–time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild–moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV(1) in the whole cohort (r=−0.71, p<0.001) and patients alone (r=−0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=−0.55, p=0.0015) and patients (r=−0.71, p<0.001) and peak exercise tidal volume (r=−0.58, p=0.0062 and r=−0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=−0.65, p<0.001) and patients considered alone (r=−0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=−0.69, p<0.001) and patients (r=−0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity

Hypercalcemia associated with a parathyroid cyst.

Parathyroid cysts are rare. When they do occur they usually have no demonstrable endocrine function, but may cause respiratory distress by tracheal compression or may be mistakenly diagnosed as thyroid carcinomas or adenomas. We report a case of a parathyroid cyst which presented with hypercalcemia. CASE REPORT: A fifty eight year old man undergoing routine investigations was found to have hypercalcaemia. His calcium level was elevated to 3.63 mmol/l and the serum parathyroid hormone level was 18.4 pmol/l (normal range 1.0- 5.3). Serum alkaline phosphatase was at the upper limit of normal at 1 1 3U/1. X-ray of the renal tract revealed no evidence of calcification. He was asymptomatic and had no palpable neck mass. Ultrasound examination revealed a 3 cm cyst-like structure inferior and posterior to the left lobe of the thyroid, with a well defined wall approximately 2 mm thick. Exploration of the neck revealed a large cyst (6.5 x 5 x 3 cm), which was removed and found to weigh 57 g. Three other parathyroid glands with a normal appearance were found. Macroscopic examination of the removed specimen showed a smooth lined cyst containing greasy, pearly material. Histology revealed a fibrous lined cyst, containing several islands of parathyroid tissue with clear cell cytology and moderate nuclear pleomorphism. Post-operatively serum calcium returned to normal. The patient was discharged on the fourth post-operative day. DISCUSSION Many theories have been advanced regarding the aetiology of parathyroid cysts. Goris1 was the first to report a case. Nylander2 has suggested that they arise from remnants of the third or fourth pharangeal pouch or are vestigia

Long‐term corticosteroid use, adrenal insufficiency and the need for steroid‐sparing treatment in adult severe asthma

Funder: AstraZeneca; Id: http://dx.doi.org/10.13039/100004325Abstract: Secondary adrenal insufficiency (AI) occurs as the result of any process that disrupts normal hypothalamic and/or anterior pituitary function and causes a decrease in the secretion of steroid hormones from the adrenal cortex. The most common cause of secondary AI is exogenous corticosteroid therapy administered at supraphysiologic dosages for ≥ 1 month. AI caused by oral corticosteroids (OCS) is not well‐recognized or commonly diagnosed but is often associated with reduced well‐being and can be life‐threatening in the event of an adrenal crisis. Corticosteroid use is common in respiratory diseases, and asthma is a representative condition that illustrates the potential challenges and opportunities related to corticosteroid‐sparing therapies. For individuals with severe asthma (approximately 5%–10% of all cases), reduction or elimination of maintenance OCS without loss of control can now be accomplished with biologic therapies targeting inflammatory mediators. However, the optimal strategy to ensure early identification and treatment of AI and safe OCS withdrawal in routine clinical practice remains to be defined. Many studies with biologics have involved short evaluation periods and small sample sizes; in addition, cautious approaches to OCS tapering in studies with a placebo arm, coupled with inconsistent monitoring for AI, have contributed to the lack of clarity. If the goal is to greatly reduce and, where possible, eliminate long‐term OCS use in severe asthma through the increasing adoption of biologic treatments, there is an urgent need for clinical trials that address both the speed of OCS withdrawal and how to monitor for AI

Seasonal and dietary influences on adipose tissue and systemic gene expression in control and previously laminitic ponies

The aims of the study were to determine whether adipose tissue global gene expression (i) differs between never laminitic (NL) and previously laminitic (PL) ponies; (ii) is influenced by season and/or a diet designed to simulate spring grass and (iii) differences seen also occur systemically in peripheral blood mononuclear cells (PBMCs). Subcutaneous adipose tissue and PBMCs were obtained from six NL and six PL ponies on three occasions; summer, winter (season study) and in winter after consuming a diet simulating spring grass for seven days (diet study). Adipose tissue global gene expression was determined using a 44K equine specific microarray, validated using multiplex quantitative real time PCR (qRT-PCR) and analysed using GeneSpring software and Ingenuity Pathway Analysis. PBMC gene expression was quantified using qRT-PCR. The total number of genes whose expression differed (=2-fold change, p=0.01) between PL and NL ponies was greater in summer (192 genes) compared to winter (58 genes); 40/192 genes influenced by disease in the summer were also seasonally regulated and were predominantly associated with inflammation. The genes modified by dietary intervention and PBMC gene expression did not follow the same pattern as the season study. Thus, adipose tissue global gene expression differed between NL and PL ponies most in summer compared to winter, and these differentially expressed genes predominantly related to inflammation