High altitude journeys and flights are associated with the increased risk of flares in IBD patients

Background: There is increasing evidence that hypoxia induces inflammation in the gastrointestinal tract. The clinical impact of hypoxia in patients with inflammatory bowel disease (IBD) is so far poorly investigated. Aim: We wanted to evaluate if flights and journeys to regions >= 2000 meter above sea level are associated with the occurrence of flares in IBD patients in the following 4 weeks. Methods: A questionnaire was completed by inpatients and outpatients of the IBD clinics of three tertiary referral centers presenting with an IBD flare. Patients were inquired about their habits in the 4 weeks prior to the flare. Patients with flares were matched with an IBD group in remission during the observation period (according to age, gender, smoking habits, and medication). Results: A total of 103 IBD patients were included (43 Crohn's disease (CD), whereof 65% female, 60 ulcerative colitis, whereof 47% female, mean age 39.3 ± 14.6 years for CD and 43.1 ± 14.2 years for UC). Fifty-two patients with flares were matched to 51 patients without flare. Overall, IBD-patients with flares had significantly more frequently a flight and/or journey to regions >= 2000 meters above sea level in the observation period compared to the patients in remission (21/52 (40.4%) vs. 8/51 (15.7%), p = 0.005). There was a statistically significant correlation between the occurrence of a flare and a flight and/or journey to regions >= 2000 meters above sea level among CD patients with flares as compared to CD patients in remission (8/21 (38.1%) vs. 2/22 (9.1%), p = 0.024). A trend for more frequent flights and high-altitude journeys was observed in UC patients with flares (13/31 (41.9%) vs. 6/29 (20.7%), p = 0.077). Mean flight duration was 5.8 ± 4.3 hours. The groups were controlled for the following factors (always flare group cited first): age (39.6 ± 13.4 vs. 43.5 ± 14.6, p = 0.102), smoking (16/52 vs. 10/51, p = 0.120), regular sports activities (32/52 vs. 33/51, p = 0.739), treatment with antibiotics in the 4 weeks before flare (8/52 vs. 7/51, p = 0.811), NSAID intake (12/52 vs. 7/51, p = 0.221), frequency of chronic obstructive pulmonary disease (both groups 0) and oxygen therapy (both groups 0). Conclusion: IBD patients with a flare had significantly more frequent flights and/or high-altitude journeys within four weeks prior to the IBD flare compared to the group that was in remission. We conclude that flights and stays in high altitude are a risk factor for IBD flares.

Regulation of the akt signalling in human skeletal muscle atrophy

Abstract : The term "muscle disuse" is often used to refer collectively to reductions in neuromuscular activity as observed with sedentary lifestyles, reduced weight bearing, cancer, chronic obstructive pulmonary disease, chronic heart failure, spinal cord injury, sarcopenia or exposure to microgravity (spaceflight). Muscle disuse atrophy, caused by accelerated proteolysis, is predominantly due to the activation of the ATP-dependent ubiquitin (Ub) proteasome pathway. The current advances in understanding the molecular factors contributing to the Ub-dependent proteolysis process have been made mostly in rodent models of human disease and denervation with few investigations performed directly in humans. Recently, in mice, the genes Atrogin-1 and MuRF1 have been designated as primary candidates in the control of muscle atrophy. Additionally, the decreased activity of the Akt/GSK-3ß and Akt/mTOR pathways has been associated with a reduction in protein synthesis and contributing to skeletal muscle atrophy. Therefore, it is now commonly accepted that skeletal muscle atrophy is the result of a decreased protein synthesis concomitant with an increase in protein degradation (Glass 2003). Atrogin-1 and MuRF1 are genes expressed exclusively in muscle. In mice, their expression has been shown to be directly correlated with the severity of atrophy. KO-mice experiments showed a major protection against atrophy when either of these genes were deleted. Skeletal muscle hypertrophy is an important function in normal postnatal development and in the adaptive response to exercise. It has been shown, in vitro, that the activation of phosphatidylinositol 3-kinase (PI-3K), by insulin growth factor 1 (IGF-1), stimulates myotubes hypertrophy by activating the downstream pathways, Akt/GSK-3ß and Akt/mTOR. It has also been demonstrated in mice, in vivo, that activation of these signalling pathways causes muscle hypertrophy. Moreover, the latter were recently proposed to also reduce muscle atrophy by inhibiting the FKHR mediated transcription of several muscle atrophy genes; Atrogin-1 and MuRF1. Therefore, these targets present new avenues for developing further the understanding of the molecular mechanisms involved in both skeletal muscle atrophy and hypertrophy. The present study proposed to investigate the regulation of the Akt/GSK-3ß and Akt/mTOR signalling pathways, as well as the expression levels of the "atrogenes", Atrogin-1 and MuRF1, in four human models of skeletal muscle atrophy. In the first study, we measured the regulation of the Akt signalling pathway after 8 weeks of both hypertrophy stimulating resistance training and atrophy stimulation de-training. As expected following resistance training, muscle hypertrophy and an increase in the phosphorylation status of the different members of the Akt pathway was observed. This was paralleled by a concomitant decrease in FOXO1 nuclear protein content. Surprisingly, exercise training also induced an increase in the, expression of the atrophy genes and proteins involved in the ATP-dependant ubiquitin-proteasome system. On the opposite, following the de-training period a muscle atrophy, relative to the post-training muscle size, was measured. At the same time, the phosphorylation levels of Akt and GSK-3ß were reduced while the amount of FOXO1 in the nucleus increased. After the atrophy phase, there was also a reduction in Atrogin-1 and MuRF1 contents. In this study, we demonstrate for the first time in healthy human skeletal muscle, that the regulation of Akt and its downstream targets GSK-3ß, mTOR and FOXO1 are associated with both thé skeletal muscle hypertrophy and atrophy processes. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of both upper and lower motor neurons, which leads to severe muscle weakness and atrophy. All measurements were performed in biopsies from 22 ALS patients and 16 healthy controls. ALS patients displayed an increase in Atrogin-1 mRNA and protein content which was associated with a decrease in Akt activity. However there was no difference in the mRNA and phospho-protein content of FOXO1, FOXO3a, p70S6K and GSK-3ß. The transcriptional regulation of human Atrogin-1 may be controlled by an Akt-mediated transcription factor other than FKHR or via an other signalling pathway. Chronic complete spinal cord injury (SCI) is associated with severe muscle atrophy which is linked to co-morbidity factors such as diabetes, obesity, lipid disorders and cardiovascular diseases. Molecular mechanisms associated with chronic complete SCI-related muscle atrophy are not well understood. The aim of the present study was to determine if there was an increase in catabolic signalling targets such as Atrogin-1, MuRF1, FOXO and myostatin, and decreases in anabolic signalling targets such as IGF, Akt, GSK-3ß, mTOR, 4E-BP1 and p-70S6K in chronic complete SCI patients. All measurements were performed in biopsies taken from 8 complete chronic SCI patients and 7 age matched healthy controls. In SCI patients when compared with controls, there was a significant reduction in mRNA levels of Atrogin1, MuRF1 and Myostatin. Protein levels for Atrogin-1, FOX01 and FOX03a were also reduced. IGF-1 and both phosphorylated GSK-3ß and 4E-BP1 were decreased; the latter two in an Akt and mTOR independent manner, respectively. Reductions in Atrogin-1, MuRF1, FOXO and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. The downregulation of signalling proteins regulating anabolism such as IGF, GSK3ß and 4E-BP1 would reduce the ability to increase protein synthesis rates in this chronic state of muscle wasting. The molecular mechanisms controlling age-related skeletal muscle loss in humans are poorly understood. The present study aimed to investigate the regulation of several genes and proteins involved in the activation of key signalling pathways promoting muscle hypertrophy such as GH/STAT5/IGF, IGF/Akt/GSK-3ß/4E-BP1 and muscle atrophy such as TNFα/SOCS3 and Akt/FOXO/Atrogin-1 or MuRF1 in muscle biopsies from 13 young and 16 elderly men. In the older, as compared with the young subjects, TNFα and SOCS-3 were increased while growth hormone receptor protein (GHR) and IGF-1 mRNA were both decreased. Akt protein levels were increased however no change in phosphorylated Akt content was observed. GSK-3ß phosphorylation levels were increased while 4E-BP1 was not changed. Nuclear FKHR and FKHRL1 protein levels were decreased, with no changes in their atrophy target genes, Atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signalling proteins such as GHR, IGF and Akt. TNFα, SOCS-3 and myostatin are potential candidates influencing this anabolic perturbation. In conclusion our results support those obtained in rodent or ín vitro models, and demonstrate Akt plays a pivotal role in the control of muscle mass in humans. However, the Akt phosphorylation status was dependant upon the model of muscle atrophy as Akt phosphorylation was reduced in all atrophy models except for SCI. Additionally, the activity pattern of the downstream targets of Akt appears to be different upon the various human models. It seems that under particular conditions such as spinal cord injury or sarcopenia, .the regulation of GSK-3ß, 4eBP1 and p70S6K might be independent of Akt suggesting alternative signalling pathways in the control of these the anabolic response in human skeletal muscle. The regulation of Atrogin-1 and MuRF1 in some of our studies has been shown to be also independent of the well-described Akt/FOXO signalling pathway suggesting that other transcription factors may regulate human Atrogin-1 and MuRF1. These four different models of skeletal muscle atrophy and hypertrophy have brought a better understanding concerning the molecular mechanisms controlling skeletal muscle mass in humans.

Walking activity measured by accelerometry during respiratory rehabilitation.

PURPOSE: Activity monitoring is considered a highly relevant outcome measure of respiratory rehabilitation. This study aimed to assess the usefulness of a new accelerometric method for characterization of walking activity during a 3-week inpatient rehabilitation program. METHODS: After individual calibration of the accelerometer at different walking speeds, whole-day physical activity was recorded for 15 patients with chronic obstructive pulmonary disease on the first and the last days of the program, and for 10 healthy subjects. Data were expressed as percentage of time spent in inactivity, low level activity, and medium level activity, with the latter corresponding to usual walking speed. RESULTS: The patients spent more time being inactive and less time walking than healthy subjects. At the end of the rehabilitation program, medium level activity had increased from 4% to 7% of total recording time. However, the change was not significant after periods of imposed exercise training were excluded. Walking activity increased to a greater degree among the patients with preserved limb muscle strength at entry to the program. Although health status scores improved, the changes did not correlate with the changes in walking activity. CONCLUSION: The findings lead to the conclusion that this new accelerometric method provides detailed analysis of walking activity during respiratory rehabilitation and may represent an additional useful measure of outcome.

Chronic Airflow Obstruction Briefing

The Chronic Conditions Hub is a website that brings together information on chronic health conditions. It allows you to easily access, manage and share relevant information resources. The Chronic Conditions Hub includes the Institute of Public Health in Ireland’s (IPH) estimates and forecasts of the number of people living with chronic conditions. On the Chronic Conditions Hub you will find: - A Briefing for each condition - Detailed technical documentation - Detailed national and sub-national data that can be downloaded or explored using online data tools - A prevalence tool that allows you to calculate prevalence figures for your population data Chronic airflow obstruction (CAO) is a chronic lung condition that interferes with normal breathing. For the purpose of this briefing, CAO includes chronic obstructive pulmonary disease (COPD), chronic bronchitis and emphysema. CAO is responsible for a substantial amount of early deaths, reduced quality of life and significant costs to the health and social care system and to the economy. The World Health Organization estimates that COPD is the fourth leading cause of death worldwide and predicts that it will soon become the third leading cause of death.

Chronic Airflow Obstruction Briefing: Technical Documentation

Chronic airflow obstruction (CAO) is a chronic lung condition that interferes with normal breathing. CAO includes chronic obstructive pulmonary disease (COPD), chronic bronchitis and emphysema. IPH has systematically estimated and forecast the prevalence of CAO on the island of Ireland. This document details the methods used to calculate these estimates and forecasts.

IPH response to NICE consultation on new indicators for Quality and Outcomes Framework (QOF)

IPH responded to the consultation on potential new indicators for the 2013/14 Quality and Outcomes Framework (QOF) in the UK. The 20 potential new indicators relate to chronic obstructive pulmonary disease (COPD), heart failure, coronary heart disease, diabetes, depression, hypertension, rheumatoid arthritis, asthma and cancer. The consultation asked people to consider whether there were any barriers to the implementation of the care described by any of the indicators; whether there were potential unintended consequences to the implementation of any of the indicators; whether there was potential for differential impact (in respect of age, disability, gender reassignment, pregnancy and maternity, race, religion or belief, sex and sexual orientation); and whether the indicators may have an adverse impact in different groups in the community.”

Prevalence of chronic conditions – Chronic Airflow Obstruction

IPH has estimated and forecast clinical diagnosis rates of CAO among adults for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007. The data describe the number of people who report that they have experienced doctor-diagnosed chronic bronchitis, chronic obstructive lung (pulmonary) disease, or emphysema in the previous 12 months (annual clinical diagnosis). Data is available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data are based on the Health and Social Wellbeing Survey 2005/06. The data describe the number of people who report that they have experienced doctor-diagnosed COPD or chronic obstructive pulmonary disease eg chronic bronchitis / emphysema or both disorders at any time in the past (lifetime clinical diagnosis). Data are available by age and sex for each Local Government District in Northern Ireland. Clinical diagnosis rates in the Republic of Ireland relate to the previous 12 months and are not directly comparable with clinical diagnosis rates in Northern Ireland which relate to anytime in the past.   The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

End of life trajectories across conditions

The findings of Pinnock and colleagues’ study on the longitudinal perspectives of people with severe chronic obstructive pulmonary disease (COPD) have implications for other non-malignant conditions.To read the 'BMJ' news article in full.

Get Healthwise this new year!

The Public Health Agency is encouraging people with specific health conditions to join the Healthwise scheme – a free 12 week physical activity programme to get their new year off to a healthy start. The scheme is available at registered leisure centres and Healthy Living Centres (HLCs) within the Belfast and South Eastern Health and Social Care Trust areas and is for people with certain health conditions who have been referred by their GP, nurse or other health professionals. The scheme is suitable for those with: • high blood pressure; • a body mass index (BMI) of more than 25; • asthma or chronic obstructive pulmonary disease (COPD); • diabetes; • osteoporosis; • hypertension; • coronary heart disease and associated risk factors; • anxiety; • stress; • depression.

Age does not hamper the response to pulmonary rehabilitation of COPD patients

Pulmonary rehabilitation (PR) improves health status and exercise tolerance, but not respiratory function in patients with chronic obstructive pulmonary disease (COPD). The objective of the study was to identify predictors of improvement in the 6-min walked distance (6'WD) in elderly COPD patients after PR. Methods: this was a prospective observational study performed in an ambulatory rehabilitation setting. The authors enrolled 74 patients aged 65-83 years (mean: 74.2, SD: 4.4) with stable COPD in GOLD stage 3-4. About half (45.6%) of them had a basal O2 saturation of 90% or less. After a baseline multi-dimensional assessment, patients underwent a 20-session rehabilitation cycle including training of the upper and lower extremities, and respiratory exercises, along with education sessions.

Clinical characteristics and outcome of patients admitted to a medico- surgical ICU requiring non invasive ventilation (NIV) for hypercapnic respiratory failure

Introduction Because it decreases intubation rate and mortality, NIV has become first-line treatment in case of hypercapnic acute respiratory failure (HARF). Whether this approach is equally successful for all categories of HARF patients is however debated. We assessed if any clinical characteristics of HARF patients were associated with NIV intensity, success, and outcome, in order to identify prognostic factors. Methods Retrospective analysis of the clinical database (clinical information system and MDSi) of patients consecutively admitted to our medico-surgical ICU, presenting with HARF (defined as PaCO2 > 50 mmHg), and receiving NIV between May 2008 and December 2010. Demographic data, medical diagnoses (including documented chronic lung disease), reason for ICU hospitalization, recent surgical interventions, SAPS II and McCabe scores were extracted from the database. Total duration of NIV and the need for tracheal intubation during the 5 days following the first hypercapnia documentation, as well as ICU, hospital and one year mortality were recorded. Results are reported as median [IQR]. Comparisons were carried out with Chi2 or Kruskal-Wallis tests, p<0.05 (*). Results Two hundred and twenty patients were included. NIV successful patients received 16 [9-31] hours of NIV for up to 5 days. Fifty patients (22.7%) were intubated 11 [2-34] hours after HARF occurence, after having receiving 10 [5-21] hours of NIV. Intubation was correlated with increased ICU (18% vs. 6%, p<0.05) and hospital (42% vs. 31%, p>0.05) mortality. SAPS II score was related to increasing ICU (51 [29-74] vs. 23 [12-41]%, p<0.05), hospital (37% [20-59] vs 20% [12-37], p<0.05) and one year mortality (35% vs 20%, p<0.05). Surgical patients were less frequent among hospital fatalities (28.8% vs. 46.3%, p<0.05, RR 0.8 [0-6-0.9]). Nineteen patients (8.6%) died in the ICU, 73 (33.2%) during their hospital stay and 108 (49.1%) were dead one year after HARF. Conclusion The practice to start NIV in all suitable patients suffering from HARF is appropriate. NIV can safely and appropriately be used in patients suffering from HARF from an origin different from COPD exacerbation. Beside usual predictors of severity such as severity score (SAPS II) appear to be associated with increased mortality. Although ICU mortality was low in our patients, hospital and one year mortality were substantial. Surgical patients, although undergoing a similar ICU course, had a better hospital and one year outcome.

Multimorbidity in the older population: CARDI research brief

New research funded by the Centre for Ageing Research and Development in Ireland (CARDI) finds that people suffering from two or more chronic conditions are 20 times more likely to report disability than those with none. The study examines the prevalence of two or more chronic conditions, known as multimorbidity, and its impact on quality of life and disability in older people. The research Multimorbidity and Disability in the Older Population of Ireland, studied eight chronic conditions: cancer; heart attack; angina; stroke; diabetes; asthma; chronic obstructive pulmonary disease (COPD) and musculoskeletal pain (including rheumatism, arthritis and back pain). Musculoskeletal pain was the most widely reported condition across the island with a prevalence of 40%, followed by diabetes (7%) and angina (6%). Asthma and COPD have the same levels of prevalence, 5%, while cancer and stroke were reported less frequently (1-2%). The study also revealed some clear differences in the prevalence of chronic diseases between ROI and NI. Angina was reported far more frequently in NI, 10% compared to 4% in ROI. So too was musculoskeletal pain, 55% compared to 35% in ROI while asthma was reported more frequently in ROI, 6% compared to 3% in NI.

Trends in the main diseases in an internal medicine ward, 2003-2011

Introduction : Population aging leads to a considerable increase in the prevalence of specific diseases. We aimed to assess if those changes were already reflected in an Internal Medicine ward. Methods : Anonymous data was obtained from the administrative database of the department of internal medicine of the Lausanne University Hospital (CHUV). All hospitalizations of adult (>=18 years) patients occurring between 2003 and 2011 were included. Infections, cancers and diseases according to body system (heart, lung...) were defined by the first letter of the ICD-10 code for the main cause of hospitalization. Specific diseases (myocardial infarction, heart failure...) were defined by the first three letters of the ICD-10 codes for the main cause of hospitalization. Results : Data from 32,741 hospitalizations occurring between 2003 and 2011 was analyzed. Cardiovascular (ICD-10 code I) and respiratory (ICD-10 code J) diseases ranked first and second, respectively, and their ranks did not change during the study period (figure). Digestive and endocrine diseases decreased while psychiatric diseases increased from rank 9 in 2003 to rank 6 in 2011 (figure). Among specific diseases, pneumonia (organism unspecified, code J18) ranked first in 2003 and second in 2011. Acute myocardial infarction (code I21) ranked second in 2003 and third in 2011. Chronic obstructive pulmonary disease with acute lower respiratory infection (code J44) ranked third in 2003 and decreased to rank 8 in 2011. Conversely, heart failure (code I50) increased from rank 8 in 2003 to rank 1 in 2011 and delirium (not induced by alcohol and other psychoactive substances, code F05) increased from below rank 20 in 2003 to rank 4 in 2011. For more details, see table. Conclusion : In less than 10 years, considerable changes occurred in the presentation of patients attending an Internal Medicine ward. The changes in diseases call for adaptations in hospital staff and logistics.

L'hyperréactivité bronchique et son importance pour le clinician [Bronchial hyperresponsiveness and its importance for the clinician].

Asthma is a chronic inflammatory airway disease, characterised by bronchial hyperresponsiveness causing bronchoconstriction, and thereby provoking typical symptoms (dyspnoea, cough, wheezing). Bronchial hyperres- ponsiveness indicates a temporary airflow limitation when exposed to a bronchoconstricting stimulus. Its measurement by challenge tests can be a valuable tool for confirming or excluding asthma, as well as for evaluating the efficacy of treatment. However, the origin of bronchial hyperresponsiveness is multifactorial and the different challenge tests are not equivalent. Direct challenge tests, like methacholine, mainly reflect chronic airway remo- delling, whereas indirect tests, like mannitol, better reflect bronchial inflammation.

Enfermedad pulmonar obstructiva crónica: proceso asistencial integrado. 2ª ed

En noviembre de 2015, se ha publicado la 3ª edición de este proceso (http://hdl.handle.net/10668/2125). Existe una guía de información para pacientes "Conozca cómo vivir mejor con la EPOC" basada en la 2ª edición de este Proceso.