Association between undiagnosed obstructive sleep apnea and severe course of COVID-19: a prospective observational study.

PURPOSE: Obstructive sleep apnea (OSA) is associated with many long-term health consequences. We hypothesized that previously unrecognized and untreated OSA may be associated with more severe respiratory failure in hospitalized patients with COVID-19. METHODS: Patients hospitalized in the Pulmonology Department with confirmed COVID-19, University Hospital in Kraków, Poland, between September 2020 and April 2021 were enrolled. OSA screening questionnaires including Epworth Sleepiness Scale (ESS), STOP-BANG, Berlin questionaire (BQ), OSA-50, and No-SAS were completed. Polygraphy was performed after > 24 h without requirement for supplemental oxygen. RESULTS: Of 125 patients with median age of 61.0 years, 71% of whom were male. OSA was diagnosed in 103 patients (82%) and was categorized as mild, moderate, and severe in 41 (33%), 30 (24%), and 32 (26%), respectively. Advanced respiratory support was introduced in 85 patients (68%), and 8 (7%) patients eventually required intubation. Multivariable analysis revealed that increased risk of requirement for advanced respiratory support was associated with higher respiratory event index (OR 1.03, 95%CI 1.00 to 1.07), oxygen desaturation index (OR 1.05, 95%CI 1.02 to 1.10), and hypoxic burden (1.02 95% CI 1.00 to 1.03) and lower minimal SpO2 (OR 0.89, 95%CI 0.81 to 0.98), but not with results of OSA screening tools like BQ score (OR 0.66, 95%CI 0.38 to 1.16), STOP-BANG score (OR 0.73, 95%CI 0.51 to 1.01), NoSAS score (OR 1.01, 95%CI 0.87 to 1.18), or OSA50 score (OR 0.84, 95%CI 0.70 to 1.01). CONCLUSION: Previously undiagnosed OSA was common among hospitalized patients who survived the acute phase of COVID-19. The degree of OSA was associated with the severity of respiratory failure.

Clinical and Polysomnographic Features Associated with Poor Sleep Quality in Patients with Obstructive Sleep Apnea.

Background and Objectives: Poor sleep quality in patients with obstructive sleep apnea (OSA) may be associated with different clinical and polysomnographic features. The aim of this study was to identify features associated with poor sleep quality in OSA patients. Materials and Methods: This was a cross-sectional study enrolling patients with OSA confirmed by polysomnography (PSG). In addition to gathering clinical data, patients were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Clinical Global Impression Scale. Univariate and multivariable analyses were performed to identify factors associated with an increased risk of poor sleep quality in this population. Results: Among 505 enrolled patients (mean age of 57.1 years, 69.7% male) poor quality of sleep (PSQI score ≥ 5) was confirmed in 68.9% of them. Multivariable analysis revealed the following factors associated with poor sleep quality: chronic heart failure (OR 3.111; 95% CI, 1.083−8.941, p = 0.035), male sex (OR 0.396; 95% CI, 0.199−0.787, p = 0.008), total ESS score (OR 1.193; 95% CI, 1.124−1.266, p < 0.001), minimal saturation during sleep (OR 1.034; 95% CI, 1.002−1.066, p = 0.036), and N3 percentage of total sleep time (OR 1.110; 95% CI, 1.027−1.200, p = 0.009). Conclusions: Our study suggests that both the female sex and coexistence of heart failure are independent risk factors for poor sleep quality. Moreover, we hypothesize that nocturnal hypoxia may lead to a misperception of sleep quality and may explain the counterintuitive association between a higher proportion of deep sleep and poor sleep quality.

Home self-monitoring in patients with asthma using a mobile spirometry system.

BACKGROUND: Self-management is an appealing strategy for prevention of asthma exacerbations. This study aimed to evaluate the feasibility and safety of a portable spirometer for unsupervised home spirometry measurements among patients with asthma. METHODS: A multi-center, prospective, single-arm, open study recruited 86 patients with controlled or partly controlled asthma (41 women, 38.6 ± 10.4 y/o and 45 men, 36.2 ± 12.1 y/o). After a training session, patients performed daily spirometry at home with the AioCare® mobile spirometry system. Each spirometry examination was recorded and evaluated according to the ATS/ERS acceptability and repeatability criteria. The primary endpoint was defined as three or more acceptable examinations in any given seven-day period (+/- 1 day) during any of the three weeks of the study. The system allowed for online review of measurements by physicians/nurses to provide feedback to patients. RESULTS: Of 78 patients with complete data, 67 (86%) achieved the primary endpoint. Seventy-five (96%) participants used the device correctly once or more, and 10 (13%) patients succeeded every single day over the three-week follow-up. The rate of acceptable spirometry examinations differed between the sites (p = 0.013). Retraining was required in 20 of 62 (32%) eligible patients, and successful in 8 individuals (40%). Satisfaction with the AioCare® system was high, 90% of respondents perceived it as useful and user-friendly. CONCLUSIONS: Self-monitoring of asthma with a connected mobile spirometer is feasible, safe and satisfactory for patients with asthma. It remains to be established whether unsupervised home spirometry measurements may improve early diagnosis and outcomes of self-management in cases of exacerbation or loss of asthma control.

Highlights BoxThis study aimed to evaluate the ability of patients with asthma to perform high-quality daily spirometry examinations at home with using the AioCare^® mobile spirometry system. The study showed that unsupervised home spirometry is safe and feasible in patients with asthma. Most patients used the device on most days of the study, and nearly 90% of all patients achieved the primary endpoint. There were no device-related adverse events.

Subphenotypes of nonsteroidal antiinflammatory disease-exacerbated respiratory disease identified by latent class analysis.

BACKGROUND: Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID-exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro-inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous. OBJECTIVE: We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA). METHODS: A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA. RESULTS: Three classes (subphenotypes) were distinguished within the NERD cohort. Class 1 subjects had mild-to-moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE4 /logPGE2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro-inflammatory LTE4 in ISS and the highest logLTE4 /logPGE2 ratio. Class 3 subjects had mild-to-moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro- (LTE4 , PGD2 and 11-dehydro-TBX2 ) was balanced by anti-inflammatory PGE2 . The value of logLTE4 /logPGE2 was between values calculated for classes 1 and 3, similarly to disease control and severity. CONCLUSIONS: LCA revealed three distinct NERD subphenotypes. Our results support a more complex pathobiology of aspirin hypersensitivity. Considering NERD heterogeneity, the relationship between inflammatory pathways and clinical manifestations of asthma may lead to more individualized treatment in difficult to treat patients in the future.

Heart Rate Variability in the Diagnostics and CPAP Treatment of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is the most common manifestation of sleep-related breathing disorders that are often accompanied by dysfunction of the autonomic nervous system. The main objective of the study was to assess the usefulness of heart rate variability (HRV) analysis in the diagnosis of patients with severe OSA and in the assessment of the effects of 3-month treatment with continuous positive airway pressure (CPAP). There were 54 patients enrolled in the study. The OSA group consisted of 39 patients suffering from severe OSA (apnea/hypopnea index >30/h), and the control group included 15 non-OSA patients with matched demographic characteristics and comorbidities. All patients underwent 24-h Holter electrocardiographic monitoring. HRV was analyzed using the time- and frequency-domains. We found that OSA patients had decreases in time-domains and increases in frequency-domains of HRV, compared to non-OSA controls, which strongly suggested a clinically disadvantageous shift in the balance of parasympathetic/sympathetic activity toward the latter. Further, CPAP treatment, partly, albeit significantly, reversed the OSA-induced changes in HRV. We conclude that HRV analysis may be of help in the diagnosis of OSA and in the monitoring of the effectiveness of treatment.

Factors affecting the choice of therapeutic regimens in asthma and chronic obstructive pulmonary disease patients and patient adherence to the therapies prescribed.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and asthma are the most common chronic respiratory diseases worldwide. At the moment, there is no information about the preferences of Polish specialists as regards the treatment of asthma and COPD or factors influencing the choice of particular treatment regimens. AIM: To determine the treatment options most commonly used by experienced pulmonologists and allergists for asthma and COPD and to identify the factors affecting the choice of a particular therapy. MATERIAL AND METHODS: The survey included 224 doctors (pulmonologists and allergists) across Poland and concerned patients diagnosed with asthma (n = 4358) and COPD (n = 3062). RESULTS: In the case of asthma, the most common therapy applied was inhaled glucocorticosteroids and long-acting ß2 agonists. According to 27.2% of doctors, combination therapy was used in 70-80% of patients while 23.7% declared that the proportion of patients receiving such a treatment exceeded 80%. In the case of COPD, anticholinergics were most frequently prescribed when inhaled glucocorticosteroids and long-acting ß2 agonists had proved insufficient. According to 21% of specialists, the percentage of patients treated so was 41-50%, while 19% declared the use of this treatment in 71-80% of patients. CONCLUSIONS: The most common treatments for asthma and COPD in Poland are inhaled glucocorticosteroids and long-acting ß2 agonists. The main factors influencing treatment decisions are the current GINA and GOLD recommendations as well as patients' age, comorbidities, and price of treatment.

Coexistence of Chronic Bronchitis in Chronic Obstructive Lung Disease.

The incidence of chronic obstructive pulmonary disease (COPD) is on the rise worldwide. Chronic bronchitis is a frequent accompaniment of COPD, which increases the burden of COPD in affected individuals. The aim of this study was to characterize the phenotype of chronic bronchitis in COPD patients. The study was based on the survey data retrospectively retrieved from the Action Health-Lung Cancer Prophylaxis and Health Care Improvement screening program that concerned all the inhabitants, aged over 40, of the Proszowice administrative region situated in the Lesser Poland Voivodeship in southern Poland. Participants with the symptoms suggestive of a lung disease were subject to further evaluation. The findings were that 546 (13.3%) out of the 4105 individuals displayed spirometry features of COPD. Symptoms of chronic bronchitis were present in 92 (16.8%) out of the COPD afflicted persons. Chronic bronchitis was commoner in current smokers and its incidence increased with increasing severity of airway obstruction. In multivariate analysis, chronic bronchitis was independently related to lower FEV1, FVC, FEV1/FVC, and to dyspnea. In regression model, factors related to increased risk of chronic bronchitis were current smoking, asthma, and lower lung function. We conclude that COPD with coexisting chronic bronchitis is linked to severer dyspnea and worse lung function. Current smoking, asthma, and lower lung function are related to increased risk of chronic bronchitis accompanying COPD.

Prevalence and burden of chronic bronchitis symptoms: results from the BOLD study.

We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.Representative population-based samples of adults aged ≥40 years were selected in participating sites. Participants completed questionnaires and spirometry. Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.Data from 24 855 subjects from 33 sites in 29 countries were analysed. There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi). Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis. Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.The prevalence of chronic bronchitis symptoms varied widely across the studied sites. Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.

[Effects of biomass combustion and occupational exposures on lung function in random population sample of Malopolska inhabitants]. / Wplyw spalania biomasy i narazen zawodowych na czynnosc pluc w losowej próbie populacyjnej mieszkanców Malopolski.

INTRODUCTION: Risk factors other than tobacco smoking contribute to about 20% of chronic obstructive pulmonary disease cases. Exposure to these risk factors and their influence on lung function has not been adequately studied in the population of Malopolska. MATERIAL AND METHODS: In random population sample of adults at least forty years old, residents of 2 districts of Malopolska, data on exposure to known and probable respiratory risk factors were collected using questionnaire. All subjects without contraindications performed pre- and post-bronchodilatator spirometry. RESULTS: We analyzed data from 618 subjects; 94,8% subjects lived for longer than 6 months in a dwelling where stove using coal or wood has been used for cooking and/or heating. At the time of study as many as 32.5% subjects were still using coal or wood for cooking or heating. Coal or wood were used as fuel on average for more than 30 years; 67% of subjects have ever worked in professions carrying a risk of exposure to potential respiratory risk factors. We have identified an independent relationship of farming with lower FEV1/FVC values as well as increased chronic obstructive pulmonary disease risk. CONCLUSIONS: Significant proportion of Malopolska inhabitants has been exposed to risks associated with cooking or heating with coal or wood. In the studied population farming was related to increased risk of chronic obstructive respiratory disease.

Impact of bariatric surgery on obstructive sleep apnea severity and continuous positive airway pressure therapy compliance-prospective observational study.

To evaluate association between bariatric surgery and changes in obstructive sleep apnea (OSA) severity and sleep architecture was as well as to asses continuous positive airway pressure (CPAP) effectiveness and compliance. We enrolled patients undergoing bariatric surgery. Polysomnography was performed in each patient preoperatively and 12 months after the procedure in a subgroup of patients diagnosed with OSA. STOP-BANG, Epworth Sleepiness Scale (ESS) and Berlin questionnaire scores were obtained pre- and postoperatively. CPAP compliance data was recorded during follow-up hospitalization. Among 44 patients with median age of 49.5 years, predominantly women (68.2%) pre- and postoperative polysomnography was performed. We observed significant improvement in STOP-BANG (6.0 vs. 3.0, p < 0.001) and ESS (12.0 vs. 5.0, p < 0.001) scores, apnea-hypopnea index (44.9 vs. 29.2, p < 0.001), oxygen desaturation index (43.6 vs. 18.3, p < 0.001) and sleep architecture parameters. CPAP compliance was poor with a median percentage of days with CPAP use accounting to 49.3%. Bariatric surgery is associated with a significant decrease in the number of sleep-related respiratory disturbances, as well as improvement of sleep efficiency. Postoperative CPAP therapy compliance was poor despite low rate of OSA resolution. This study suggests that patients with OSA undergoing bariatric surgery require postoperative reassessment.

Eicosanoids and Eosinophilic Inflammation of Airways in Stable COPD.

PURPOSE: Lipid mediators, particularly eicosanoids, are associated with airway inflammation, especially with the eosinophilic influx. This study aimed to measure lipid mediators and cells in induced sputum, that could possibly reflect the inflammatory process in the bronchial tree of COPD subjects. PATIENTS AND METHODS: Eighty patients diagnosed with COPD and 37 healthy controls participated in the study. Induced sputum samples were ascertained for differential cell count and induced sputum supernatant concentrations of selected eicosanoids by the means of gas chromatography/mass spectrometry and high-performance liquid chromatography/tandem mass spectrometry. RESULTS: Increased sputum eosinophilia was associated with higher concentrations of selected proinflammatory eicosanoids. In COPD subjects prostaglandin D2 and 11-dehydro-thromboxane B2 correlated negatively with airway obstruction measured by FEV1 and FEV1/FVC values. COPD subjects with disease exacerbations during past 12 months had significantly higher concentrations of prostaglandin D2, 12-oxo-eicosatetraenoic acid and 5-oxo-eicosatetraenoic acid. CONCLUSION: Stable COPD is often associated with eosinophil influx in the lower airways and elevated concentrations of eicosanoids that is reflected by some disease characteristics.

High-flow nasal oxygen therapy in the treatment of acute respiratory failure in severe COVID-19 pneumonia: a prospective observational study.

INTRODUCTION: A significant proportion of patients with COVID­19 present with a rapidly progressing severe acute respiratory failure. OBJECTIVES: We aimed to assess the efficacy of high­flow nasal oxygen (HFNO) therapy in severe acute respiratory failure in the course of COVID­19 in a noncritical care setting as well as to identify predictors of HFNO failure. PATIENTS AND METHODS: This prospective observational study was conducted between March and December 2020. We enrolled all consecutive patients hospitalized with confirmed SARS­CoV­2 infection in whom HFNO therapy was used. The primary outcome was death or endotracheal intubation within 30 days from admission. RESULTS: Of the 380 patients with COVID­19 hospitalized at our tertiary center, 116 individuals (30.5%) requiring HFNO due to severe pneumonia were analyzed. The primary outcome occurred in 54 patients (46.6%). The overall 30­day mortality rates were 30.2% (35 out of 116 patients) in the entire cohort and 64.7% (34 out of 51 patients) among individuals requiring endotracheal intubation. A multivariable analysis revealed that the ROX index (the ratio of oxygen saturation / fraction of inspired oxygen to respiratory rate) below 3.85 measured within the first 12 hours of therapy was related to increased mortality (hazard ratio, 5.86; 95% CI, 3.03-11.35) compared with the ROX index of 4.88 or higher. CONCLUSIONS: The results of our study suggest that nearly half of patients treated with HFNO due to severe COVID­19 pneumonia will require mechanical ventilation. The ROX index is a useful tool for predicting HFNO failure in this population.

Can alveolar hypoventilation due to kyphoscoliosis be a contraindication to driving?

Road accidents are among the main fatalities worldwide and drowsy driving is a significant cause of road deaths where drivers are at fault. There are well known diseases which impair sensory and cognitive functions and can cause sleepiness during driving. Such diseases can be an important contraindication to driving because they may have an adverse effect on its safety. Thus, medical examinations for drivers should also be directed at identifying any possible conditions posing risks for driving safety. Occupational medicine specialists should look for symptoms of locomotor and sleep-related breathing disorders as these are medical conditions which could preclude a person from driving. In this case report, the authors describe a professional driver with chest deformity and present a pioneering attempt at assessing his medical fitness to drive. It is also explained why scoliosis can impair driving ability and how it should be diagnosed and treated. Finally, the authors describe how they used driving simulator tests as part of their diagnosis and suggest a relevant treatment regimen. Int J Occup Med Environ Health. 2019;32(5):735-45.

Symptoms of chronic bronchitis in individuals without chronic obstructive pulmonary disease: prevalence, burden, and risk factors in southern Poland.

Introduction Chronic bronchitis (CB) symptoms are commonly reported in individuals without chronic obstructive pulmonary disease (COPD), but CB is rarely diagnosed in this population. Objectives We aimed to determine the prevalence and burden of CB, as well as its risk factors, in a population of patients without COPD. Patients and methods Data from the "Health Action" program (a lung cancer prevention and health care improvement program conducted in Proszowice County, Poland) were used. All county inhabitants aged 40 years or older without COPD were invited to participate. As part of the program, a questionnaire was administered to assess CB symptoms and risk factors. Spirometry at baseline and after the bronchodilator test was also performed. Results CB symptoms were present in 9.1% of the 3558 participants. The prevalence of CB in the study population was 7.12% (95% CI, 6.70-7.56). Patients with CB had more dyspnea and more often received medical treatment for lung disease or were hospitalized for respiratory disorders than patients without CB. CB was associated with worse lung function and a worse score in the modified Medical Research Council Dyspnea Scale even after adjustment for possible confounders. In a multivariate analysis, male sex, age over 70 years, current smoking, passive exposure to tobacco smoke, gas or wood heating, occupational exposure to chemical agents, lower forced expiratory volume in 1 second, and asthma correlated with an increased risk of CB. Conclusions CB symptoms are common in individuals without COPD aged 40 years or older and are associated with more dyspnea irrespective of lung function and comorbidities.

Pulmonary prevention program in the Proszowice county: description and results.

INTRODUCTION: In the Proszowice county, both lung cancer and chronic obstructive pulmonary disease (COPD) are more common in comparison with other regions of Poland. The purpose of this study was to provide a report on a prevention program carried out in the area to reduce the burden of COPD and lung cancer in the region. MATERIAL AND METHODS: The program consisted of the following: active prevention - questionnaire survey offered to every county inhabitant aged at least 40 and chest X-ray and spirometry performed in selected subjects; and passive prevention - covering multiple educational activities promoting healthy lifestyle. Data obtained from questionnaire survey and spirometry were further analyzed. RESULTS: Education program covered all local children aged 13-15, a majority of adolescents and a significant proportion of adult inhabitants of the county. Questionnaire data were obtained from 14,455 subjects (about 70% of county inhabitants). On the basis of the questionnaire results, the participants were selected to undergo spirometry (5,816 subjects) and chest X-ray (5,514 subjects). Current smokers constituted 24.2% of the total number of participants (33.3% of men and 16.8% of women). Electronic cigarettes were currently used by 0.65% of the subjects. Negative impact of occupational exposures (including farming) on lung function and the presence of respiratory symptoms was observed. Basing on post-bronchodilator spirometry, COPD was diagnosed in 13.2% of the subjects. Physician's diagnosis of asthma was reported by 7.2%. CONCLUSION: Educational activities and questionnaire-based study were targeted at and reached the majority of the county inhabitants. The study provided data on the prevalence and risk factors of COPD, asthma and respiratory symptoms in the Proszowice region.

Systemic prostacyclin and thromboxane production in obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea increases the risk of cardiovascular diseases. Alternations in prostacyclin and thromboxane concentrations and balance could constitute one of mechanisms linking sleep apnea and cardiovascular events. Thus we aimed to assess the concentrations of 6-keto-prostaglandin F1α (6-keto-PGF1α) (metabolite of prostacyclin) and thromboxane B2 (TXB2) (metabolite of thromboxane A2) in urine and blood of obstructive sleep apnea patients and controls (snoring subjects with otherwise normal polysomnogram). MATERIAL AND METHODS: Overnight urine and morning blood samples were taken from subjects and controls at baseline and in sleep apnea group during continuous positive airway pressure (CPAP) treatment. Samples were analyzed using mass chromatography/gas spectrometry. RESULTS: We analyzed data from 26 obstructive sleep apnea subjects (mean apnea-hypopnea index 45.4±17.3) and 22 well-matched controls. At baseline sleep apnea patients, when compared to controls, have higher 6-keto-PGF1α in urine (0.89±0.15 vs 0.34±0.06, p=0.01) and blood (24.49±1.54 vs 19.70±1.77, p=0.04). TXB2 levels in urine and blood were not different across groups. CPAP treatment significantly decreased 6-keto-PGF1α in urine (0.92±0.17 vs 0.22±0.10, p=0.04), but not in blood. TXB2 levels during CPAP treatment did not change significantly. CONCLUSIONS: These results suggest augmented systemic prostacyclin production in obstructive sleep apnea patients, which potentially could constitute a protective mechanism against detrimental effects of sleep apnea.

Modulation of inflammatory and hemostatic markers in obstructive sleep apnea patients treated with mandibular advancement splints: a parallel, controlled trial.

STUDY OBJECTIVE: Obstructive sleep apnea (OSA) is associated with systemic inflammation and a hypercoagulable state. The current study aim was to investigate whether mandibular advancement splint (MAS) therapy affects inflammatory and hemostatic parameters in patients with mild-to-moderate OSA. METHODS: Twenty-two patients with mild-to-moderate OSA and 16 control subjects were studied. OSA subjects were treated with a titratable MAS for 6 months. Baseline plasma C-reactive protein, interleukin-1ß, interleukin-10, interleukin-6, P-selectin, fibrinogen, D-dimer, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex, activated thrombin-activatable fibrinolysis inhibitor (TAFIa), 6-keto-PGF1α, glucose, and fibrin clot lysis time (CLT) were measured in all subjects. After 3 months of MAS therapy, measurements were repeated for the 22 patients, and after 6 months all measurements were repeated for all study subjects. RESULTS: MAS treatment reduced significantly AHI at 3 months (24 vs 13.1/h) and further improved it at 6 months (13.1 vs 7.05/h). Compared with controls, OSA subjects had a significant higher baseline mean levels of fibrinogen, TAFIa, 6-keto-PGF1α, and glucose. MAS treatment significantly improved levels of IL-1ß, D-dimer, TAFIa, and CLT. Despite residual apneas, MAS treatment group presented similar measured homeostatic and inflammatory levels to controls except for glucose. CONCLUSION: Treatment with MAS in mild-to-moderate OSA subjects improves the inflammatory profile and homeostatic markers. CITATION: Nizankowska-Jedrzejczyk A; Almeida FR; Lowe AA; Kania A; Nastalek P; Mejza F; Foley JH; Nizankowska-Mogilnicka E; Undas A. Modulation of inflammatory and hemostatic markers in obstructive sleep apnea patients treated with mandibular advancement splints: a parallel, controlled trial.

Susceptibility to chronic mucus hypersecretion, a genome wide association study.

BACKGROUND: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. METHODS: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10(-9)) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. CONCLUSIONS: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.