International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

Predominance of Comorbidities in the Detriment of Daily Activity in Sarcoidosis Patients.

Sarcoidosis may affect lung function, working ability, overall mobility, and daily activity. In the present study we performed an analysis of clinical settings in patients with sarcoidosis to disentangle its influence on daily physical activity (PA). PA assessment (number of steps per day, daily energy expenditure) was performed by accelerometry during consecutive 7 days after discharge from hospital. Thirty patients with sarcoidosis, aged 46.4 ± 10.5, were enrolled in the study. Clinical data (age, gender, steroid consumption, weight, and comorbidities), lung function tests (forced expiratory volume in one second - FEV1, forced vital capacity - FVC, and lung diffusion for carbon monoxide - DLCO), mobility (6-minute walk test - 6 MWT) and physical performance (oxygen consumption at anaerobic threshold - VO2/AT) were estimated. The mean daily PA (5214 ± 2699 steps/day) and VO2max (22.3 ± 7.0 ml/kg/min) were lower when referenced to the age-group predicted values. A significant greater daily PA was observed in sarcoidosis patients without comorbidities compared with those having more than two comorbidities (p = 0.046). No association was found between steroid use, lung function, and 6MWT. Daily PA was associated with patients aerobic efficacy and VO2max (r = 0.38, p < 0.04). The findings demonstrate a significant influence of comorbidities on sarcoidosis patients' exercise tolerance and daily PA. Special treatment considerations, including the potential impact of comorbidities, may help optimize exercise regimes, link physical activity with health, and prevent sarcoidosis complications.

Physical Functioning and Symptoms of Chronic Fatigue in Sarcoidosis Patients.

Scientific reports underscore the importance of measuring the health-related quality of life in sarcoidosis patients. The present study seeks to define how sarcoidosis patients' quality of life, daily physical activity, and physical performance are related to each other. Seventeen patients (mean age 46.8 ± 8.8 years) suffering from sarcoidosis completed the following questionnaires: the fatigue assessment scale (FAS), the quality of life scale (SF-36 questionnaire), and the Borg dyspnea scale. Physical activity (PA) was assessed using accelerometry. Respiratory function, consisting of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory volume in one second as a percentage of vital capacity (FEV1/%FVC), and diffusing capacity of the lungs for carbon monoxide (DLCO), were assessed. In addition, performance in 6-min walk test (MWT), aerobic capacity assessed from maximal oxygen uptake (VO2max), and the metabolic equivalent of task (MET) were evaluated. We found that daily PA (4566 ± 2378 steps/day) and VO2max (21.8 ± 5.9 ml/kg/min) were lower in sarcoidosis patients than the known predicted values in healthy age-matched individuals. There were significant inverse associations between the FAS score and 6MWT (r = -0.62; p < 0.01), and between SF-36 score and 6MWT (r = -0.55; p < 0.03). In contrast, SF-36 scores associated with fatigue and dyspnea scores (r = 0.72; p < 0.001 and r = 0.85; p < 0.001). These findings imply that sarcoidosis patients are less active compared with healthy subjects. The FAS and SF-36 scales seem to be effective tools for assessing the severity of fatigue in sarcoidosis patients.

Expression of the JAK/STAT Signaling Pathway in Bullous Pemphigoid and Dermatitis Herpetiformis.

A family of eleven proteins comprises the Janus kinases (JAK) and signal transducers and activators of transcription (STAT) signaling pathway, which enables transduction of signal from cytokine receptor to the nucleus and activation of transcription of target genes. Irregular functioning of the cascade may contribute to pathogenesis of autoimmune diseases; however, there are no reports concerning autoimmune bullous diseases yet to be published. The aim of this study was to evaluate the expression of proteins constituting the JAK/STAT signaling pathway in skin lesions and perilesional area in dermatitis herpetiformis (DH) and bullous pemphigoid (BP), as well as in the control group. Skin biopsies were collected from 21 DH patients, from 20 BP patients, and from 10 healthy volunteers. The localization and expression of selected STAT and JAK proteins were examined by immunohistochemistry and immunoblotting. We found significantly higher expression of JAK/STAT proteins in skin lesions in patients with BP and DH, in comparison to perilesional skin and the control group, which may be related to proinflammatory cytokine network and induction of inflammatory infiltrate in tissues. Our findings suggest that differences in the JAK and STAT expression may be related to distinct cytokines activating them and mediating neutrophilic and/or eosinophilic infiltrate.

Respiratory Function and Language Abilities of Profoundly Deaf Adolescents with and without Cochlear Implants.

The objective of the study was to investigate whether hearing loss has an effect on the ventilatory functional capability and whether possible deviations of ventilatory variables from the reference ranges could have to do with the language abilities of deaf adolescents. Spirometric evaluations were performed in 72 prelingually profoundly deaf adolescents with and without cochlear implants (CI) and compared with the results of a control group consisting of 48 participants with normal hearing (CG). The deaf adolescents showed a significantly lower vital capacity (VC), forced vital capacity (FVC), and expiratory flows (PEF and MEF) compared with their hearing peers. The adolescents with CI demonstrated predominantly the oral communication mode, which however did not affect the students' education achievements. Perseverance of oral communication was also associated with higher FVC and PEF, compared with deaf participants without CI. We conclude that sensory deprivation of prelingually deaf adolescents affects the respiratory system function. The use of oral communication seems to have beneficial effects on respiratory performance in profoundly deaf adolescents.

Endurance training and the risk of bronchial asthma in female cross-country skiers.

Exercise is one of the crucial factors responsible for asthma development and exacerbation. The purpose of the present study was to assess the risk of bronchial asthma in female athletes. Spirometric evaluations and physical exercise test were performed and exhaled nitric oxide (eNO) levels were measured in 12 female elite cross-country skiers. Serum concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) were measured in all subjects before exercise, immediately after it, and after 15 min of recovery. Peak eNO values were 18.7±4.8 (ppb) and did not confirm the risk of early bronchial asthma symptoms. A graded exercise test caused significant increases in TNF-α and IL-1ß concentration (p<0.05) after 15 min of recovery. A significant negative correlation was found between resting and post-exercise eNO and IL-6 levels (p<0.01). Our study did not confirm an increased risk of bronchial asthma or respiratory tract inflammatory conditions among female cross-country skiers exposed to physical exertion.

Fatigue in sarcoidosis and exercise tolerance, dyspnea, and quality of life.

Fatigue is one of the major symptoms reported by sarcoidosis patients. The relationship between fatigue and clinical course of sarcoidosis remains unclear. The aim of the study was to evaluate the relationship between fatigue and lung function tests, exercise tolerance, dyspnea, and quality of life among sarcoidosis patients. One hundred eleven sarcoidosis patients completed the following questionnaires: Fatigue and Assessment Scale (FAS), Quality of Life Scale (SF-36), and dyspnea scales: Medical Research Council Questionnaire, Baseline Dyspnea Index, and Oxygen Cost Diagram. Clinical parameters (FVC, FEV1, DLCO, VO2, and VO2/AT, and work load) were derived from the patients' medical files. The exercise tolerance was the only clinical parameter associated with fatigue (Max. Work Load -0.65, VO2 -0.42, VO2/AT -0.51). No correlations were found between FAS and spirometry or diffusing tolerance. Fatigue correlated with all dyspnea domains by means of (r values ranging from 0.47 to 0.77 in multivariate regression analysis) and with quality of life in SF-36 questionnaire (r values ranging from -0.33 to -0.83). We conclude that FAS seems a reliable and valid indicator of dyspnea level, quality of life, and exercise tolerance in sarcoidosis patients.

IGF-1 response to arm exercise with eccentric and concentric muscle contractions in resistance-trained athletes with left ventricular hypertrophy.

The study aimed at evaluating changes in plasma levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), testosterone, growth hormone (GH), cortisol, and insulin in resistance-trained male athletes with (n=9) and without (n=9) left ventricular hypertrophy (LVH) in response to eccentric (ECC) and concentric (CON) arm exercise. 10 age-matched healthy non-trained subjects served as controls. M-mode and 2D Doppler echocardiography were used to estimate LV mass.Resting IGF-1 concentration was higher in LVH athletes compared to controls (52 ± 5 nM vs. 46 ± 7 nM, p<0.05). ECC exercise resulted in higher (p<0.05) serum IGF-1 concentrations in athletes with LVH (70 ± 11 nM, n=9) compared to those without LVH (62 ± 10 nM, n=9), and to untrained controls (54 ± 6 nM). Both CON and ECC exercise resulted in higher serum IGFBP-3 levels in LVH athletes compared to controls (242 ± 57 and 274 ± 58, athletes, vs. 215 ± 63 and 244 ± 67, controls, nM, p<0.05). In ECC exercise, GH concentrations were lower in LVH than in non-LVH athletes (4.7 ± 2.1 vs. 6.1 ± 1.8 ng mL(-1), p<0.05). No differences in other hormones were found between groups. In conclusion, LVH is accompanied by elevated resting serum IGF-1 and enhanced response to eccentric arm exercise. These findings suggest a role of IGF-1, possibly released from contracting muscle, in stimulating LV hypertrophy in resistance training.

Pulmonary rehabilitation in patients referred for lung transplantation.

Effectiveness of pulmonary rehabilitation in patients with chronic obstructive lung diseases, cystic fibrosis, and interstitial lung disease is well documented but little is known about the results of pulmonary rehabilitation in patients referred for lung transplantation. The purpose of this study is to prospectively examine the efficacy of Nordic walking, a low cost, accessible, and proven beneficial form of physical exercise, as a form of pulmonary rehabilitation in patients referred for lung transplantation. Twenty-two male patients referred for lung transplantation at the Department of Lung Diseases and Tuberculosis in Zabrze, Poland, were invited to take part in the study. The rehabilitation program, which was conducted for 12 weeks, was based on Nordic walking exercise training with ski poles. Lung function tests (FVC, FEV1), mobility (6 min walking test (6MWT)), rating of dyspnea (Oxygen Cost Index, MRC and Baseline Dyspnea Index), and quality of life assessments (SF-36) were performed before and after the completion of the exercise program. No adverse events were observed after completing the pulmonary rehabilitation program in patients referred for lung transplantation. After 12 weeks of pulmonary rehabilitation with Nordic walking we observed a significant increase in the mean distance walked in the 6MWT (310.2 m vs. 372.1 m, p < 0.05). The results of lung function tests also showed improvement in FVC. There were no significant differences in the perception of dyspnea before and after completing the rehabilitation program. General health and quality of life questionnaire (SF-36) showed improvement in the domain of social functioning (p < 0.05). In conclusion, pulmonary rehabilitation with a Nordic walking program is a safe and feasible physical activity in end-stage lung disease patients referred for lung transplantation and results in improvements in patients' mobility and quality of life.

Spirometric measurements and physical efficiency in children and adolescents with hearing and visual impairments.

The objective of the study was to investigate whether a sensory impairment has an effect on functional capabilities of the respiratory system and whether possible deviations from reference ranges of selected parameters might indicate a decrease of physical efficiency. Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), forced expiratory flow of 25-75% (FEF25-75), maximum voluntary volume (MVV), and maximum oxygen uptake VO2 max were measured in 86 deaf and 102 blind children and adolescents, and in a matched group of hearing controls. We found a significant influence of deafness on PEF (P<0.01), FEF25-75 (P<0.05), and MVV (P<0.05). As compared with the control subjects, mean VC was significantly lower in blind adolescents (P<0.05). Our results seem to suggest that both sensory defects during childhood and adolescence affect functional capabilities of the respiratory system.

Spirometric values and aerobic efficiency of children and adolescents with hearing loss.

Vital capacity (VC), forced expiratory volume in 1 s (FEV(1)), peak expiratory flow (PEF), mean forced expiratory flow (FEV(25-75)), and maximum voluntary volume (MVV) were measured in 36 girls and 36 boys with hearing loss and compared with the same number of normal healthy children, all subjects were aged 10-16 years. They participated in an exercise test to calculate VO(2 max) in order to determine their physical efficiency. We found that all spirometric indices tended to be lower in deaf children, in all age-groups studied and irrespective of gender, compared with their hearing counterparts; the differences assumed significance with respect to PEF and MVV (P<0.05). Moreover, some deaf children had an appreciably lower level of VO(2 max) compared with hearing children. Our results demonstrate that sensory deprivation of deaf children affects functional capabilities of the respiratory system.

A new method of synthesis of fluorescently labelled oligonucleotides and their application in DNA sequencing.

A new approach to the chemical synthesis of oligodeoxynucleotides bearing reporter functional groups at base residues of 3'-end nucleosides is reported. Applications of the 3'-end fluorescently labelled primers for automated DNA sequencing are shown.