Haulage Cycles Identification for Wheeled Transport in Underground Mine Using Neural Networks.

The task of ore transportation is performed in all mines, regardless of their type (open pit/underground) or mining process. A substantial number of enterprises utilize wheeled machines to perform ore haulage, especially haul trucks and loaders. These machines' work consists of repeating cycles, and each cycle can be divided into 4 operations: loading, driving with full box/bucket, unloading and driving with empty box/bucket. Monitoring this process is essential to create analytical tools that support foremen and other management crew in achieving effective and optimal production and planning activities. Unfortunately, information gathered regarding the process is frequently based on operators' oral testimony. This process not only allows for abuse but is also a repetitive and tedious task that must be performed by foremen. The time and attention of foremen is valuable as they are responsible for managing practically everything in their current mine section (machines, operators, works, repairs, emergencies, safety, etc.). Therefore, the automatization of the described process of information gathering should be performed. In this article, we present two neural network models (one for haul trucks and one for loaders) build for detecting work cycles of the ore haulage process. Both models were built utilizing a 2-stage approach. In the first stage, the models' structures were optimized, while the second was focused on optimizing hyperparameters for the structure with best performance. Both of the proposed models were trained using data collected from on-board monitoring systems over hundreds of the machines' work hours and utilized the same input features: vehicle speed, fuel consumption, selected gear and engine rotational speed. Models have been subjected to comprehensive testing during which the efficiency and stability of the model responsible for haul trucks was proven. Results for loaders were not as high quality for haul trucks; however, some interesting facts were discovered that indicate possible directions for future development.

Fuzzy Risk-Based Maintenance Strategy with Safety Considerations for the Mining Industry.

Enterprises today are increasingly seeking maintenance management strategies to ensure that their machines run faultlessly. This problem is particularly relevant in the mining sector, due to the demanding working conditions of underground mines and machines and equipment-operating regimes. Therefore, in this article, the authors proposed a new approach to mining machinery maintenance management, based on the concept of risk-based maintenance (RBM) and taking into account safety issues. The proposed method includes five levels of analysis, of which the first level focuses on hazard analysis, while the next three are connected with a risk evaluation. The final level relates to determining the RBM recommendations. The recommendations are defined in relation to the three main improvement areas: maintenance, safety, and resource availability/allocation. The proposed approach is based on the use of fuzzy logic. To present the possibilities of implementing our method, a case study covering the operation of selected mining machinery in a selected Polish underground mine is presented. In the case of mining machinery, fourteen adverse-event scenarios were identified and investigated; general recommendations were also given. The authors have also indicated further directions of research work to optimize system maintenance strategies, based on the concept of risk-based maintenance. Additionally, the discussion about the implementation possibilities of the approach developed herein is provided.

Application of Wearable Computer and ASR Technology in an Underground Mine to Support Mine Supervision of the Heavy Machinery Chamber.

Systems that use automatic speech recognition in industry are becoming more and more popular. They bring benefits especially in cases when the user's hands are often busy or the environment does not allow the use of a keyboard. However, the accuracy of algorithms is still a big challenge. The article describes the attempt to use ASR in the underground mining industry as an improvement in the records of work in the heavy machinery chamber by a foreman. Particular attention was paid to the factors that in this case will have a negative impact on speech recognition: the influence of the environment, specialized mining vocabulary, and the learning curve. First, the foreman's workflow and documentation were recognized. This allowed for the selection of functionalities that should be included in the application. A dictionary of specialized mining vocabulary and a source database were developed which, in combination with the string matching algorithms, aim to improve correct speech recognition. Text mining analysis, machine learning methods were used to create functionalities that provide assistance in registering information. Finally, the prototype of the application was tested in the mining environment and the accuracy of the results were presented.

Unique sleep-stage transitions determined by obstructive sleep apnea severity, age and gender.

In obstructive sleep apnea, patients' sleep is fragmented leading to excessive daytime sleepiness and co-morbidities like arterial hypertension. However, traditional metrics are not always directly correlated with daytime sleepiness, and the association between traditional sleep quality metrics like sleep duration and arterial hypertension is still ambiguous. In a development cohort, we analysed hypnograms from mild (n = 209), moderate (n = 222) and severe (n = 272) obstructive sleep apnea patients as well as healthy controls (n = 105) from the European Sleep Apnea Database. We assessed sleep by the analysis of two-step transitions depending on obstructive sleep apnea severity and anthropometric factors. Two-step transition patterns were examined for an association to arterial hypertension or daytime sleepiness. We also tested cumulative distributions of wake as well as sleep-states for power-laws (exponent α) and exponential distributions (decay time τ) in dependency on obstructive sleep apnea severity and potential confounders. Independent of obstructive sleep apnea severity and potential confounders, wake-state durations followed a power-law distribution, while sleep-state durations were characterized by an exponential distribution. Sleep-stage transitions are influenced by obstructive sleep apnea severity, age and gender. N2 → N3 → wake transitions were associated with high diastolic blood pressure. We observed higher frequencies of alternating (symmetric) patterns (e.g. N2 → N1 → N2, N2 → wake → N2) in sleepy patients both in the development cohort and in a validation cohort (n = 425). In conclusion, effects of obstructive sleep apnea severity and potential confounders on sleep architecture are small, but transition patterns still link sleep fragmentation directly to obstructive sleep apnea-related clinical outcomes like arterial hypertension and daytime sleepiness.

Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database.

BACKGROUND AND OBJECTIVE: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. METHODS: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2 ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). RESULTS: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. CONCLUSION: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

BACKGROUND AND OBJECTIVE: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHODS: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. RESULTS: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). CONCLUSION: Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Chronic obstructive pulmonary disease guidelines in Europe: a look into the future.

Clinical practice guidelines are ubiquitous and are developed to provide recommendations for the management of many diseases, including chronic obstructive pulmonary disease. The development of these guidelines is burdensome, demanding a significant investment of time and money. In Europe, the majority of countries develop their own national guidelines, despite the potential for overlap or duplication of effort. A concerted effort and consolidation of resources between countries may alleviate the resource-intensity of maintaining individual national guidelines. Despite significant resource investment into the development and maintenance of clinical practice guidelines, their implementation is suboptimal. Effective strategies of guideline dissemination must be given more consideration, to ensure adequate implementation and improved patient care management in the future.

Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects.

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 × 10-8) and PPP4R4/SERPINA1 (P = 1.01 × 10-8) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, ∼0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline.

This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations.Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation.The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.

Prevention of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline.

This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory Society and the American Thoracic Society.Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable (benefits) and undesirable consequences (burden in the form of adverse effects and cost), quality of evidence, feasibility, and acceptability of various interventions, the Task Force made recommendations for mucolytic, long-acting muscarinic antagonist, phosphodiesterase-4 inhibitor (roflumilast) and macrolide therapy, as well as a conditional recommendation against fluoroquinolone therapy. All of the recommendations were conditional, except for a strong recommendation for the use of a long-acting antimuscarinic agent versus a long-acting ß2-adrenergic, indicating that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.The guideline summarises the evidence and provides recommendations for pharmacological therapy for the prevention of COPD exacerbations.

Exome Array Analysis Identifies a Common Variant in IL27 Associated with Chronic Obstructive Pulmonary Disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) susceptibility is in part related to genetic variants. Most genetic studies have been focused on genome-wide common variants without a specific focus on coding variants, but common and rare coding variants may also affect COPD susceptibility. OBJECTIVES: To identify coding variants associated with COPD. METHODS: We tested nonsynonymous, splice, and stop variants derived from the Illumina HumanExome array for association with COPD in five study populations enriched for COPD. We evaluated single variants with a minor allele frequency greater than 0.5% using logistic regression. Results were combined using a fixed effects meta-analysis. We replicated novel single-variant associations in three additional COPD cohorts. MEASUREMENTS AND MAIN RESULTS: We included 6,004 control subjects and 6,161 COPD cases across five cohorts for analysis. Our top result was rs16969968 (P = 1.7 × 10(-14)) in CHRNA5, a locus previously associated with COPD susceptibility and nicotine dependence. Additional top results were found in AGER, MMP3, and SERPINA1. A nonsynonymous variant, rs181206, in IL27 (P = 4.7 × 10(-6)) was just below the level of exome-wide significance but attained exome-wide significance (P = 5.7 × 10(-8)) when combined with results from other cohorts. Gene expression datasets revealed an association of rs181206 and the surrounding locus with expression of multiple genes; several were differentially expressed in COPD lung tissue, including TUFM. CONCLUSIONS: In an exome array analysis of COPD, we identified nonsynonymous variants at previously described loci and a novel exome-wide significant variant in IL27. This variant is at a locus previously described in genome-wide associations with diabetes, inflammatory bowel disease, and obesity and appears to affect genes potentially related to COPD pathogenesis.

A review of national guidelines for management of COPD in Europe.

The quality of care can be improved by the development and implementation of evidence-based treatment guidelines. Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years. Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process. Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden. The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines. There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia. However, there are differences in the definitions of patient subgroups and other recommended treatments.

Efficacy and safety of aclidinium/formoterol versus salmeterol/fluticasone: a phase 3 COPD study.

The efficacy and safety of twice-daily aclidinium bromide/formoterol fumarate was compared with that of salmeterol/fluticasone propionate in patients with stable, moderate-to-severe chronic obstructive pulmonary disease (COPD).AFFIRM COPD (Aclidinium and Formoterol Findings in Respiratory Medicine COPD) was a 24-week, double-blind, double-dummy, active-controlled study. Patients were randomised (1:1) to aclidinium/formoterol 400/12 µg twice-daily via Genuair/Pressair or salmeterol/fluticasone 50/500 µg twice-daily via Accuhaler. The primary end-point was peak forced expiratory volume in 1 s (FEV1) at week 24. Other end-points included Transition Dyspnoea Index (TDI) focal score at week 24, TDI and St George's Respiratory Questionnaire (SGRQ) responders, COPD Assessment Test and SGRQ scores, assessment of COPD symptoms and exacerbations, use of reliever medication, and device preference. Adverse events were monitored throughout.In total, 933 patients were eligible (mean age 63.4 years, 65.1% male). Aclidinium/formoterol was superior to salmeterol/fluticasone in peak FEV1 and noninferior in TDI. Health status and reduction in exacerbation risk were similar in both groups. While both treatments were well tolerated, pneumonia occurred less frequently with aclidinium/formoterol than salmeterol/fluticasone.In stable COPD, aclidinium/formoterol significantly improved bronchodilation versus salmeterol/fluticasone, with equivalent benefits in symptom control and reduction in exacerbation risk. Both treatments were well tolerated and treatment-related adverse events were less common with aclidinium/formoterol.

The national alpha-1 antitrypsin deficiency registry in Poland.

The alpha-1 antitrypsin deficiency (AATD) targeted screening program, together with the National Registry, were established in Poland in 2010 soon after the AATD diagnostics became available. Between 2010 and 2014 a total of 2525 samples were collected from respiratory patients countrywide; 55 patients with severe AAT deficiency or rare mutations were identified and registered, including 36 PiZZ subjects (65%). The majority of AATD patients were diagnosed with COPD (40%) or emphysema (7%), but also with bronchial asthma (16%) and bronchiectasis (13%). Therefore, the registry has proved instrumental in setting-up the AATD-dedicated network of respiratory medical centres in Poland. Since augmentation therapy is not reimbursed in our country, the smoking cessation guidance, optimal pharmacotherapy of respiratory symptoms as well the early detection, and effective treatment of exacerbations is absolutely essential.

Chronic obstructive pulmonary disease in the awareness of Polish society. Report from the public opinion survey by the Polish Respiratory Society and TNS Polska.

INTRODUCTION: It is assumed that signs of chronic obstructive pulmonary disease (COPD) can be found in 9.3% subjects of more than 40 years of age in general population in Poland. The aim of the presented survey was to assess knowledge of COPD in adult general population in Poland. MATERIAL AND METHODS: The study was performed in June 2013 in a representative sample of 1,000 persons of at least 15 years of age in Poland, using standardized direct interview. RESULTS: In 2013 only 3% Polish people admitted they had ever heard of COPD and knew what the acronym meant. Further 11% persons admitted having heard the term but had no further knowledge of the subject. Thus, the total of 14% persons in general population had previously heard of COPD albeit superficially. This figure is slightly higher as compared to the study performed in 2004. The second part of the study was performed in patients with COPD. Patients perceive the disease as a limiting factor in their daily lives, including negative impact on physical activity, causing loss of physical attractiveness (more often reported by women) or hurting their image of a strong and caring person (more often reported by men). The disease demands re-evaluation of the previous lifestyle, alienates patients from other people, and generates financial burden. Half of the entire studied general population either does not have any associations concerning potential causes of COPD or report various erroneous connotations (e.g. excessive alcohol consumption as a cause of the disease). Even patients with COPD have a similar view on causes of the disease. Importantly, the study revealed that awareness of the disease in smokers does not essentially differ from that in general public. Half of the res pondents admitted having no knowledge on prevention of COPD. CONCLUSIONS: There is an urgent need for widespread public education on preventive measures. Study results support the need of educating both healthy subjects and patients with COPD as to how effectively reduce the risk of developing the disease. One third of all respondents has no assumptions in this regard (i.e. explicitly declares having no knowledge at all on the subject), and more than 40% subjects have various misconceptions. Educators should therefore spread information about the disease but also correct these misconceptions.

Causes of deaths in COPD patients in primary care setting--a 6-year follow-up.

INTRODUCTION: COPD is one of the most frequent respiratory diseases responsible for patients' disability and mortality. In 2005 a single primary care practice, COPD was diagnosed in 183 out of 1,960 eligible subjects ≥ 40 years (9.3%). The aim of this study was to assess mortality rate and causes of deaths in this group after 6 years. MATERIAL AND METHODS: In 2011 we invited all 183 patients with COPD recognised in 2005. We performed spirometry, physical examination, questionnaire of respiratory symptoms, smoking habits, concomitant diseases and treatment. Information about deaths was taken from primary care register, furthermore, family members were asked to deliver medical documentation or death certificate. RESULTS: In 2011 we studied only 74 subjects (40.4%), 43 subjects died (23.5%) and 66 subjects were lost from the follow-up (36.1%). Cardiovascular diseases were the most frequent causes of deaths - 21 subjects (48.8%) (heart attack - 8 patients and stroke - 8 patients). Respiratory failure in the course of COPD exacerbation was the cause of 10 deaths (23.3%). Neoplastic diseases lead to 9 deaths (20.9%) (lung cancer 7 patients). Renal insufficiency was responsible for one death (2.325%), and the causes of 2 deaths remained unknown (4.65%). Subjects who died (predominantly males) were older, had higher MRC score and lower FEV1. CONCLUSIONS: Study performed six years after COPD diagnosis revealed that 23.5% of subjects died. The main causes of deaths were the following: cardiovascular diseases (mainly heart attack and stroke), COPD exacerbations and lung cancer (more than 75%). Death risk in COPD patients was associated with age, male sex, dyspnoea and severity of the disease.

Pilot program on distance training in spirometry testing - the technology feasibility study.

INTRODUCTION: Office spirometry has been widely used in recent years by general practitioners in primary care setting, thus the need for stricter monitoring of the quality of spirometry has been recognized. MATERIAL AND METHODS: A spirometry counseling network of outpatients clinics was created in Poland using portable spirometer Spirotel. The spirometry data were transferred to counseling centre once a week. The tests sent to the counseling centre were analyzed by doctors experienced in the analysis of spirometric data. In justified cases they sent their remarks concerning performed tests to the centres via e-mail. RESULTS: We received 878 records of spirometry tests in total. Data transmission via the telephone was 100% effective. The quality of spirometry tests performed by outpatients clinics was variable. CONCLUSIONS: The use of spirometers with data transfer for training purposes seems to be advisable. There is a need to proper face-to-face training of spirometry operators before an implementation of any telemedicine technology.

Venous thromboembolism and sarcoidosis: co-incidence or coexistence?

The association between venous thromboembolism (VTE) and sarcoidosis has been reported recently, nevertheless the true incidence of co-incident sarcoidosis and VTE is unknown. Sarcoidosis as a chronic disease of immune dysregulation might be associated with an increased risk of VTE. The mechanisms responsible for VTE development are not clear and may be influenced by several factors: activity of inflammation, clinical characteristics of sarcoidosis and comorbidities. Pulmonary embolism (PE) as a potentially fatal condition should be considered in all of the patients with sarcoidosis in whom worsening of the respiratory status is diagnosed. A high plasma D-dimers (DD) level may be suggestive of VTE, nevertheless elevated plasma DD should be interpreted with caution, in the context of the active inflammatory process. If sarcoidosis appears to be one of risk factors for VTE development, further investigations are needed to define the pro-thrombotic phenotype of this disease.

Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP.

Multiple intergenic single-nucleotide polymorphisms (SNPs) near hedgehog interacting protein (HHIP) on chromosome 4q31 have been strongly associated with pulmonary function levels and moderate-to-severe chronic obstructive pulmonary disease (COPD). However, whether the effects of variants in this region are related to HHIP or another gene has not been proven. We confirmed genetic association of SNPs in the 4q31 COPD genome-wide association study (GWAS) region in a Polish cohort containing severe COPD cases and healthy smoking controls (P = 0.001 to 0.002). We found that HHIP expression at both mRNA and protein levels is reduced in COPD lung tissues. We identified a genomic region located ∼85 kb upstream of HHIP which contains a subset of associated SNPs, interacts with the HHIP promoter through a chromatin loop and functions as an HHIP enhancer. The COPD risk haplotype of two SNPs within this enhancer region (rs6537296A and rs1542725C) was associated with statistically significant reductions in HHIP promoter activity. Moreover, rs1542725 demonstrates differential binding to the transcription factor Sp3; the COPD-associated allele exhibits increased Sp3 binding, which is consistent with Sp3's usual function as a transcriptional repressor. Thus, increased Sp3 binding at a functional SNP within the chromosome 4q31 COPD GWAS locus leads to reduced HHIP expression and increased susceptibility to COPD through distal transcriptional regulation. Together, our findings reveal one mechanism through which SNPs upstream of the HHIP gene modulate the expression of HHIP and functionally implicate reduced HHIP gene expression in the pathogenesis of COPD.

Nocturnal intermittent hypoxia predicts prevalent hypertension in the European Sleep Apnoea Database cohort study.

Systemic hypertension is associated with obstructive sleep apnoea syndrome (OSAS) but the pathophysiological mechanisms are incompletely understood. A collaborative European network of 24 sleep centres established a European Sleep Apnoea Database to evaluate cardiovascular morbidity associated with OSAS. 11 911 adults referred with suspected OSAS between March 2007 and September 2013 underwent overnight sleep studies, either cardiorespiratory polygraphy or polysomnography. We compared the predictive value of the apnoea-hypopnoea index (AHI) and 4% oxygen desaturation index (ODI) for prevalent hypertension, adjusting for relevant covariates including age, smoking, obesity, dyslipidaemia and diabetes. Among patients (70% male, mean±sd age 52±12 years), 78% had AHI>5 events·h(-1) and 41% systemic hypertension. Both AHI and ODI independently related to prevalent hypertension after adjustment for relevant covariates (p<0.0001 for linear trend across quartiles (Q) of severity for both variables). However, in multiple regression analysis with both ODI and AHI in the model, ODI was, whereas AHI was not, independently associated with prevalent hypertension: odds ratios (95% CI) for Q4 versus Q1 regarding ODI were 2.01 (1.61-2.51) and regarding AHI were 0.92 (0.74-1.15) (p<0.0001 and p=0.3054, respectively). This cross sectional study suggests that chronic intermittent hypoxia plays an important role in OSAS-related hypertension.