ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax.

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.

Multicentric Genome-Wide Association Study for Primary Spontaneous Pneumothorax

Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29-2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis.

Multicentric Genome-Wide Association Study for Primary Spontaneous Pneumothorax

Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29-2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis.

Multicentric genome-wide association study for primary spontaneous pneumothorax

Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22–2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08–2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29–2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis.

[The role of thoracoscopy in paediatric spontaneous pneumothorax]

Spontaneous pneumothorax in children is an emergency. A rapid and structured treatment is necessary. Indicating clinical signs are dyspnoea with unilateral reduced breath sounds and hypersonic percussion note. Chest x-ray confirms diagnosis. CT scan shows detailed information's of pathological changes in lung tissue and offers important considerations for the therapy. Today video assisted thoracoscopic surgery (VATS) takes a central role in the treatment of spontaneous pneumothorax. Thoracoscopy completes diagnosis detecting the pathologies, which were missed in imaging procedures. Definitive surgical treatment is performed simultaneously in the same anaesthesia.

Pneumotórax espontâneo primário : da incerteza etiológica ás dicotomias do tratamento

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Emphysema and secondary pneumothorax in young adults smoking cannabis

BACKGROUND: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. STUDY DESIGN: Retrospective case series. METHODS: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). RESULTS: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p=0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. CONCLUSIONS: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the future.

Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays

Background Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat (‘artificial animal’) applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Results Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. Conclusions We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain tissues support emerging, exploitable commonalities between in vivo and in vitro preparations. We conclude that experimental manipulation of endogenous cholinergic tone could offer a novel opportunity to improve the use of cortical cultures for studies of network-level mechanisms in a manner that remains largely consistent with its functional role.

Spontaneous remission of primary hyperparathyroidism in a patient with neurofibromatosis type 1: case report

Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem disorder affecting approximately 1 in 3500 individuals. Patients with the disorder can develop carcinoid tumors, medullary thyroid carcinoma, pheochromocytoma and tumor of the hypothalamus. The association of NF1 with Primary Hyperparathyroidism (HPP) is very rare. We report a 56-year-old woman with NF1 who was referred to our service because of nephrolithiasis. Physical examination revealed the characteristic signs of NF1, and her laboratory calcium profile was compatible with HPP. The patient was referred for parathyroidectomy, but during the surgical work-up she underwent spontaneous remission of her HPP. This case is significant not only for the rarity of this presentation in NF1 patients, but also because of the spontaneous remission of HPP.

Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury 3 d to 8 months earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared with untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 months. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C- and Aδ-fibers revealed SCI-induced SA generated in or near the somata of the neurons in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.

Correlates of spontaneous reporting of adverse drug reactions within primary care: the paradox of low prescribers who are high reporters

AIM(S) To examine Primary Care Trust (PCT) demographics influencing general practitioner (GP) involvement in pharmacovigilance. METHODS PCT adverse drug reaction (ADR) reports to the Yellow Card scheme between April 2004 and March 2006 were obtained for the UK West Midlands region. Reports were analysed by all drugs, and most commonly reported drugs (‘top drugs’). PCT data, adjusted for population size, were aggregated. Prescribing statistics and other characteristics were obtained for each PCT, and associations between these characteristics and ADR reporting rates were examined. RESULTS During 2004–06, 1175 reports were received from PCTs. Two hundred and eighty (24%) of these reports were for 14 ‘top drugs’. The mean rate of reporting for PCTs was 213 reports per million population. A total of 153 million items were prescribed during 2004–06, of which 33% were ‘top drugs’. Reports for all drugs and ‘top drugs’ were inversely correlated with the number of prescriptions issued per thousand population (rs = -0.413, 95% CI -0.673, -0.062, P < 0.05, and r = -0.420, 95% CI -0.678, -0.071, P < 0.05, respectively). Reporting was significantly negatively correlated with the percentages of male GPs within a PCT, GPs over 55 years of age, single-handed GPs within a PCT, the average list size of a GP within a PCT, the overall deprivation scores and average QOF total points. ADR reports did not correlate significantly with the proportion of the population over 65 years old. CONCLUSIONS Some PCT characteristics appear to be associated with low levels of ADR reporting. The association of low prescribing areas with high ADR reporting rates replicates previous findings.