Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment

TNFα‐, IL‐23‐ and IL‐17‐targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin, the presence of Langerhans cells (LCs) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL‐23/IL‐17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL‐17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air‐liquid interphase for 4 days. In a gene array analysis, we found that the two LC markers, CD1a and CD207, were among the most up‐ or downregulated genes in psoriatic skin after anti‐TNFα therapy. Validation showed that both mRNA expression and protein level followed the same pattern and became significantly upregulated after 4 days of treatment. No changes were seen after ustekinumab treatment. In the ex vivo skin model, a decrease in the CD1a level was seen after TNFα stimulation and it was caused by LC migration from epidermis. No response in LC migration was seen after IL‐17A stimulation. Taken together, we demonstrated that changes in the LC level in epidermis precede the histological and clinical changes during adalimumab treatment in psoriatic skin. Furthermore, TNFα plays a prominent role in orchestrating LC migration in the skin. This seems not to be the true for the IL‐23/IL‐17A pathway.     

Physical activity and asthma: A longitudinal and multi-country study

Objective: To investigate the impact of physical activity on asthma in middle-aged adults, in one longitudinal analysis, and one multi-centre cross-sectional analysis. Methods: The Respiratory Health in Northern Europe (RHINE) is a population-based postal questionnaire cohort study. Physical activity, height and weight were self-reported in Bergen, Norway, at RHINE II (1999–2001) and all centres at RHINE III (2010–2012). A longitudinal analysis of Bergen data investigated the association of baseline physical activity with follow-up asthma, incident asthma and symptoms, using logistic and zero-inflated Poisson regression (n = 1782). A cross-sectional analysis of all RHINE III centres investigated the association of physical activity with concurrent asthma and symptoms (n = 13,542) using mixed-effects models. Body mass index (BMI) was categorised (<20, 20–24.99, 25–29.99, 30+ kg/m²) and physical activity grouped by amount and frequency of lighter (no sweating/heavy breathing) and vigorous (sweating/heavy breathing) activity. Results: In the Bergen longitudinal analysis, undertaking light activity 3+ times/week at baseline was associated with less follow-up asthma (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.22, 0.89), whilst an effect from undertaking vigorous activity 3+ times/week was not detected (OR 1.22, 95% CI 0.44, 2.76). The associations were attenuated with BMI adjustment. In the all-centre cross-sectional analysis an interaction was found, with the association between physical activity and asthma varying across BMI categories. Conclusion: These findings suggest potential longer-term benefit from lighter physical activity, whilst improvement in asthma outcomes from increasing activity intensity was not evident. Additionally, it appears the benefit from physical activity may differ according to BMI.     

Resistance training in the early postoperative phase reduces hospitalization and leads to muscle hypertrophy in elderly hip surgery patients--a controlled, randomized study

OBJECTIVES: To better understand how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes. DESIGN: A prospective randomized, controlled study. SETTING: Bispebjerg University Hospital, Copenhagen, Denmark. PARTICIPANTS: Thirty-six patients (aged 60-86) scheduled for unilateral hip replacement due to primary hip osteoarthrosis. INTERVENTION: Patients were randomized to standard home-based rehabilitation (1 h/d x 12 weeks), unilateral neuromuscular electrical stimulation of the operated side (1 h/d x 12 weeks), or unilateral resistance training of the operated side (3/wk x 12 weeks). MEASUREMENTS: Hospital length of stay (LOS), quadriceps muscle cross-sectional area (CSA), isokinetic muscle strength, and functional performance. Patients were tested presurgery and 5 and 12 weeks postsurgery. RESULTS: Mean+/-standard error LOS was shorter for the resistance training group (10.0+/-2.4 days, P<.05) than for the standard rehabilitation group (16.0+/-7.2 days). Resistance training, but not electrical stimulation or standard rehabilitation, resulted in increased CSA (12%, P<.05) and muscle strength (22-28%, P<.05). Functional muscle performance increased after resistance training (30%, P<.001) and electrical stimulation (15%, P<.05) but not after standard rehabilitation. CONCLUSION: Postoperative resistance training effectively increased maximal muscle strength, muscle mass, and muscle function more than a standard rehabilitation regime. Furthermore, it markedly reduced LOS in elderly postoperative patients.     

Release patterns of pregnancy‐associated plasma protein A in patients with acute coronary syndromes assessed by an optimized monoclonal antibody assay

Objective. Pregnancy‐associated plasma protein A (PAPP‐A) is expressed in eroded and ruptured atheromatous plaques, and circulating levels are elevated in acute coronary syndromes (ACS). Our objective was to investigate release patterns of PAPP‐A in ACS and whether they differ among different types of ACS. Methods. In 40 patients, PAPP‐A concentrations were measured in serially collected samples assessed by a novel ELISA technique. The patients were grouped according to type of ACS. Results. Release patterns for ST elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI) showed a single substantial PAPP‐A increase shortly after pPCI, followed by an abrupt return to normal levels without secondary peaks. STEMI, high‐risk and low‐risk non‐ST elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients without pPCI showed highly variable patterns with primary peaks followed by secondary PAPP‐A increases. All patients with elevated PAPP‐A levels reached the upper reference level within 24?h. There was a significant difference in median peak levels between STEMI (23.2?mIU/L) and low‐risk ACS patients (6.35?mIU/L) (p = 0.004) and between high‐risk (median = 15.3?mIU/L) and low‐risk ACS patients (p = 0.01). Among high‐risk ACS patients, NSTEMI patients had significantly higher peak levels than UAP patients (p = 0.003). Conclusion. PAPP‐A serum levels increase above normal values within 24?h after onset of symptoms in ACS. There are significant differences in PAPP‐A peak levels and release patterns across the spectrum of ACS patients.     

Aspects of healthcare utilisation in self‐reported obstructive lung disease

Introduction: Utilisation of healthcare resources because of pulmonary diseases have previously been presented according to lung function or symptom severity. We aimed to compare the associations of symptoms and lung function to healthcare and social service utilisation in subjects with self‐reported obstructive lung diseases (OLDs) (asthma, chronic obstructive pulmonary disease, chronic bronchitis, emphysema). Materials and Methods: Of 2819 participants aged 27–82 years in the Hordaland County Respiratory Health Survey, 200 subjects (7.1%) self‐reported OLD. They answered 13 questions on respiratory symptoms and 5 questions on use of healthcare and social services. Altogether, 161 participants (81%) completed post‐bronchodilation spirometry. Results: Use of anti‐asthmatic drugs, regular physician's appointment, sick leave payment for the last 12 months, hospital admission for the last 12 months and disability pension were reported by 68%, 63%, 18%, 8% and 7% of those with self‐reported OLD, respectively. Twenty per cent of subjects with self‐reported OLD had not received any healthcare or social services. In adjusted multivariate logistic regression analyses, increase in the respiratory symptom score was significantly associated with more healthcare and social services. Lower forced expiratory volume in 1 s in % predicted, however, was not significantly associated with more use of healthcare and social services. Conclusion: The majority (80%) of subjects in a general population with self‐reported OLD received healthcare services. The utilisation of healthcare and social services was strongly associated to the burden of respiratory symptoms, and, to a lesser degree, to the level and pattern of lung function. Please cite this paper as: Nielsen R, Johannessen A, Bakke PS, Askildsen JE, Omenaas ER and Gulsvik A. Aspects of healthcare utilisation in self‐reported obstructive lung disease. The Clinical Respiratory Journal 2009; 3: 34–41.     

Exposure to second-hand smoke and reproductive outcomes depending on maternal asthma

Tobacco consumption and exposure to second-hand smoke (SHS) are associated with reduced birth weight. One issue that has not been clarified previously is that of the potential higher risk of this outcome in mothers with asthma. We assessed the role of prenatal maternal tobacco use and SHS on reproductive outcomes and assessed the interaction with maternal history of asthma. Data was collected from the INMA study, a maternal birth cohort selected from the general population established in Spain in 2002. We measured cotinine at the 32nd week of pregnancy in 2,219 females. Diagnosed maternal asthma was self-reported during pregnancy. 35% of mothers reported not being exposed to smoking or SHS during pregnancy. Active smoking (i.e. self-reported or cotinine >50 ng·mL(-1)) was related to a 134 g decrease in birth weight and a relative risk of 1.8 for small for gestational age and fetal growth restriction. These results were not modified by maternal asthma. Maternal asthma had a similar frequency in all exposure groups. Non SHS-exposed females had the lowest prevalence of asthma. SHS (i.e. cotinine 20-50 ng·mL(-1)) decreased birth weight by 32 g among those without maternal asthma, but these differences were not statistically significant (95% CI -88.76-24.76). Maternal asthma did not promote these effects. Maternal history of asthma did not modify the effects of smoking on reproductive outcomes in a cohort sampled from the general population.