The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related interstitial lung disease: a multicentre European Scleroderma Trials and Research group (EUSTAR) study.

Objectives: The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important mediators of inflammation and connective tissue remodelling. The aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) of ALOX5AP confer risk of SSc and/or SSc-related organ involvement. Methods: Seven SNPs of ALOX5AP (rs17222814, rs17216473, rs10507391, rs4769874, rs9551963, rs9315050 and rs7222842) were genotyped in a cohort of 977 patients with SSc and 558 healthy controls from centres collaborating within the European Scleroderma Trials and Research group. In 22 SSc patients, concentrations of cysteinyl LTs and LT B4 (LTB4) were measured in the supernatants of ionophore-stimulated peripheral blood mononuclear cells (PBMCs) by means of commercially available enzyme immunoassay kits. Results: Significant association was found between rs10507391 polymorphism (T/A) of ALOX5AP and the risk of SSc [odds ratio (OR) 1.27 (95% CI 1.07, 1.50), P < 0.05 vs controls], the presence of SSc-related interstitial lung disease on high-resolution CT of the lungs [OR 1.45 (95% CI 1.17, 1.79), P < 0.05 vs patients without SSc-related interstitial lung disease] as well as with restrictive ventilatory defect [forced vital capacity <70% of predicted; OR 1.51 (95% CI 1.16, 1.97), P < 0.05 vs SSc patients without pulmonary restriction]. PBMCs from SSc carriers of rs10507391 allele A synthesized greater amounts of cysteinyl LTs as compared with SSc patients with rs10507391 TT genotype ( P < 0.05). Synthesis of LTB4 did not differ significantly between the two groups. Conclusion: The results of our study indicate that the genetic variants of ALOX5AP might play a role in the development of SSc-related pulmonary fibrosis.

Efficacy of daytime transcutaneous electrical stimulation of the genioglossus muscle in patients with obstructive sleep apnea syndrome: short report.

Obstructive sleep apnea syndrome (OSAS) is characterized by hypotonia of lingual and suprahyoid muscles. Genioglossus muscle is responsible for protrusion and depression of the tongue. Its dysfunction results in occlusion of the upper airways and greater incidence of apnea-hypopnea events during sleep. The aim of this prospective study was to compare the effects of daytime transcutaneous electrical stimulation of the genioglossus muscle and standard continuous positive airway pressure (CPAP) therapy on the quality of sleep, in patients with OSAS. During a 4-week study period, 19 patients with OSAS were subjected to daytime transcutaneous electrical stimulation of the genioglossus muscle before sleep and another 19 subjects underwent standard CPAP therapy. Polysomnography (apnea-hypopnea index, AHI), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to diagnose OSAS and to verify the efficacy of both treatments. Electrical stimulation treatment was reflected by a decrease in PSQI (p = 0.012) but did not influence ESS and AHI values (p > 0.05). In turn, CPAP therapy resulted in a significant decrease in ESS and AHI values (p < 0.001) but exerted no effect on PSQI (p = 0.089). Despite improvement of sleep quality, electrical stimulation does not seem to reduce AHI values in patients with OSAS. Daytime electrical stimulation can be considered as an adjunct treatment in OSAS. Future prospective studies should center on the identification of patients with OSAS who may benefit most from transcutaneous electrical stimulation.

[Excessive daytime sleepiness and risk for obstructive sleep apnea in the public transport drivers]. / Ocena wystepowania wzmozonej sennosci w ciagu dnia oraz ryzyka obturacyjnego bezdechu podczas snu u kierowców zawodowych komunikacji miejskiej.

BACKGROUND: Obstructive sleep apnea (OSA) is a set of symptoms related to the increased upper airways resistance during sleep (due to pharyngeal walls collapse) leading to intermittent airflow obstruction in the lungs. One of the most severe OSA symptoms is excessive daytime sleepiness. Sustained daytime sleepiness may impair cognitive functions and thus influence the everyday functioning of affected person. MATERIAL AND METHODS: The aim of the study was to prospectively assess excessive daytime sleepiness and the risk for OSA in municipal bus drivers. The study was performed in a group of 103 men. The anonymous survey comprised Epworth Sleepiness Scale (ESS) for daytime sleepiness assessment and STOP-Bang Questionnaire (SBQ) for OSA risk assessment. RESULTS: In 43 (42%) respondents OSA risk was assessed as low, while moderate and high risk was observed in 55 (53%) and 5 (5%) drivers, respectively. Severe daytime sleepiness correlated positively with ESS results (r = 0.32; p < 0.05). In drivers with high OSA risk revealed in SBQ no correlation with high ESS was observed. CONCLUSIONS: In drivers with moderate and high OSA risk a sleep medicine specialist consultation with a consecutive diagnostic procedures is necessary. STOP-Bang Questionnaire and ESS are the fast tools to identify patients at increased risk for OSA.

Effectiveness and safety of a simple home-based rehabilitation program in pulmonary arterial hypertension: an interventional pilot study.

BACKGROUND: Rehabilitation plays an important role in the management of patients with pulmonary arterial hypertension (PAH) and current guidelines recommend implementation of a monitored individualized exercise training program as adjuvant therapy for stable PAH patients on optimal medical treatment. An optimal rehabilitation model for this group of patients has not yet been established. This randomized prospective study assessed the effectiveness and safety of a 6-month home-based caregiver-supervised rehabilitation program among patients with pulmonary arterial hypertension. METHODS: A total of 39 patients with PAH were divided into two groups: intervention group (16 patients), subjected to a 6-month home-based physical training and respiratory rehabilitation program adapted to the clinical status of participants, and control group (23 patients) who did not perform physical training. The 6-min walk test (6MWT), measurement of respiratory muscle strength, quality of life assessment (SF-36, Fatigue Severity Scale - FSS) were performed before study commencement, and after 6 and 12 months. Adherence to exercise protocol and occurrence of adverse events were also assessed. RESULTS: Physical training significantly improved 6MWT distance (by 71.38 ± 83.4 m after 6 months (p = 0.004), which remained increased after 12 months (p = 0.043), and respiratory muscle strength after 6 and 12 months (p < 0.01). Significant improvement in quality of life was observed after the training period with the use of the SF-36 questionnaire (Physical Functioning, p < 0.001; Role Physical, p = 0.015; Vitality, p = 0.022; Role Emotional, p = 0.029; Physical Component Summary, p = 0.005), but it did not persist after study completion. Adherence to exercise protocol was on average 91.88 ± 14.1%. No serious adverse events were noted. CONCLUSION: According to study results, the home-based rehabilitation program dedicated to PAH patients is safe and effective. It improves functional parameters and quality of life. Strength of respiratory muscles and 6MWD remain increased 6 months after training cessation. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03780803 . Registered 12 December 2018.

The influence of Multiwave Locked System (MLS) laser therapy on clinical features, microcirculatory abnormalities and selected modulators of angiogenesis in patients with Raynaud's phenomenon.

The aim of this study was to investigate the influence of the Multiwave Locked System (MLS) laser therapy on clinical features, microvascular changes in nailfold videocapillaroscopy (NVC) and circulating modulators releasing as a consequence of vascular endothelium injury such as vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2) in patients with primary and secondary Raynaud's phenomenon. Seventy-eight RP patients and 30 healthy volunteers were recruited into the study. All patients with RP received MLS laser irradiation for 3 weeks. Clinical, NVC and laboratory investigations were performed before and after the MLS laser therapy. The serum concentration of VEGF and Ang-2 were determined by an enzyme-linked immunosorbent assay (ELISA). After 3 weeks of MLS laser therapy, the clinical improvement manifested by decreasing of the number of RP attacks, mean duration of Raynaud's attack and pain intensity in RP patients was observed. After MLS laser therapy in 65% of patients with primary and in 35% with secondary RP, an increase in the loop number and/or a reduction in avascular areas in NVC were observed. In comparison with a control group, higher serum concentration of VEGF and Ang-2 in RP patients was demonstrated. After MLS laser therapy, a reduction of Ang-2 in both groups of RP patients was found. Our results suggest that NVC may reflect microvascular changes associated with clinical improvement after MLS laser therapy in patients with primary and secondary RP. Ang-2 serum levels may be a useful marker of microvascular abnormalities in RP patients treated with MLS laser therapy.

Rehabilitation of patients with obstructive sleep apnea syndrome.

The current treatment of obstructive sleep apnea syndrome (OSAS) focuses on alleviation of symptoms by increasing airway patency during sleep through positive airway pressure, oral appliances, changes in sleep position, weight loss, or surgical treatment. Continuous positive airway pressure (CPAP) is currently the treatment of choice and prevents upper airway obstruction, resulting in improved sleep architecture and daytime symptoms. Despite proven efficacy, adherence to CPAP treatment is still not efficient. The new methods of rehabilitation (exercise training programs, hypoglossal nerve stimulation) for patients with OSAS are currently modified. The aim of the present study was to present recent developments in the field of selected aspects of rehabilitation in patients with OSAS. Database search was focused on exercise training programs and electrostimulation of genioglossus muscle. The search for articles on the rehabilitation interventions for OSAS was performed using the PubMed database from 1966 to 2013. Most of the findings have shown beneficial effects of rehabilitation. In detail, we describe the recent developments and potential adverse effects of electrostimulation and physical exercises. According to the results of studies presented, the above therapy might support conventional treatment or may be an alternative for patients with poor compliance to CPAP therapy, mandibular advancement devices, or ineffective results of surgical procedures as well.

The role of leukotrienes in the pathogenesis of systemic sclerosis.

Systemic sclerosis (SSc, scleroderma) is an autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. SSc-related involvement of the lungs, heart, kidneys and/or the gastrointestinal system accounts for the increased mortality of scleroderma patients. Despite the progress which has recently been made in this field, the treatment of SSc is still unsatisfactory due to the low efficacy and/or high toxicity of available therapies. Leukotrienes are a family of lipid mediators synthesized from arachidonic acid in a process mediated by 5-lipoxygenase; they include leukotriene B4 and a group of cysteinyl leukotrienes: C4, D4, and E4. Leukotrienes play an important role in the regulation of all the processes vital to the pathogenesis of SSc, namely inflammation, vascular function and connective tissue remodeling. The available data suggests that an excessive synthesis of leukotrienes may contribute to the development and progression of SSc. Accordingly, blockade of leukotriene pathways appears to be a new, promising target for the treatment of SSc.