Analysis of possible risk factors for the severity of paediatric obstructive sleep apnoea syndrome.

PURPOSE: This study aimed to determine the effect of body mass index (BMI) percentile, asthma, sex, and age on the paediatric obstructive sleep apnoea (OSA) severity. Furthermore, to determine the possible predictive role of the BMI percentile and age in severe OSA. METHODS: This retrospective study included 921 children aged 2-18 years diagnosed with OSA by polysomnography. Analysis of Covariance (ANCOVA), Spearman's correlation, Receiver Operating Characteristics (ROC) analyses were performed and area under the curve (AUC) was determined. RESULTS: We observed a significant association between a higher BMI percentile and the severity of OSA (p < 0.001, ρ = 0.15). The correlation also was significant under (p = 0.007, ρ = 0.11) and over 7 (p = 0.0002, ρ = 0.23) years of age. There was no association between the severity of OSA and the presence of asthma (p = 0.9) or sex (p = 0.891), respectively. Age was significantly related to OSA severity (p = 0.01, ρ = 0.08). Although both the BMI percentile (0.59 AUC [0.54-0.65]) and age (0.58 AUC [0.52-0.63]) predicted severe OSA, according to the sensitivity and specificity values of the ROC curve, the association presents a slight clinical relevance. CONCLUSIONS: OSA severity is determined by the BMI percentile and age in children; however, these factors are unsuitable for predicting severe OSA in clinical practice. Based on our results, obesity is also a significant risk factor for OSA in younger children. Our study highlights that older, overweight, and obese children have a higher risk for severe OSA.

ERS statement: a core outcome set for clinical trials evaluating the management of COPD exacerbations.

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.

Dysregulation of the endothelial nitric oxide pathway is associated with airway inflammation in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is related to endothelial dysfunction and the impaired generation of nitric oxide (NO) from L-arginine by the endothelial NO synthase (eNOS). The relationship between eNOS dysfunctionality and airway inflammation is unknown. We assessed serum asymmetric and symmetric dimethylarginine (ADMA and SDMA) and nitrite/nitrate concentrations, indicators of eNOS function, in patients with COPD and correlated them with markers of inflammation. METHODS: We recruited 15 control smokers, 29 patients with stable and 32 patients with exacerbated COPD requiring hospitalization (20 of them were measured both at admission and discharge). Serum L-arginine, ADMA, SDMA, nitrite and nitrate were measured and correlated with airway inflammatory markers (fractional exhaled nitric oxide concentration - FENO, sputum nitrite and nitrate, sputum cellularity), serum C-reactive protein - CRP, white blood cell count, lung function and blood gases. ANOVA, t-tests and Pearson correlation were used (mean ± SD or geometric mean ± geometric SD for nitrite/nitrate). RESULTS: Serum L-arginine/ADMA, a marker of substrate availability for eNOS, was lower in stable (214 ± 58, p < 0.01) and exacerbated COPD (231 ± 68, p < 0.05) than in controls (287 ± 64). The serum concentration of SDMA, a competitor of L-arginine transport, was elevated during an exacerbation (0.78 ± 0.39 µM) compared to stable patients (0.53 ± 0.14 µM, p < 0.01) and controls (0.45 ± 0.14 µM, p < 0.001). ADMA correlated with blood neutrophil percentage (r = 0.36, p < 0.01), FENO (r = 0.42, p < 0.01) and a tendency for positive association was observed to sputum neutrophil count (r = 0.33, p = 0.07). SDMA correlated with total sputum inflammatory cell count (r = 0.61, p < 0.01) and sputum neutrophil count (r = 0.62, p < 0.01). Markers were not related to lung function, blood gases or CRP. L-arginine/ADMA was unchanged, but serum SDMA level decreased (0.57 ± 0.42 µM, p < 0.05) after systemic steroid treatment of the exacerbation. Serum nitrite level increased in stable and exacerbated disease (4.11 ± 2.12 and 4.03 ± 1.77 vs. control: 1.61 ± 1.84 µM, both p < 0.001). CONCLUSIONS: Our data suggest impaired eNOS function in stable COPD, which is transiently aggravated during an exacerbation and partly reversed by systemic steroid treatment. Serum ADMA and SDMA correlate with airway inflammatory markers implying a possible effect of anti-inflammatory therapy on endothelial dysfunction. Serum nitrite can serve as a compensatory pool for impaired endothelial NO generation.

A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammation.

OBJECTIVE: Extended nitric oxide (NO) analysis offers the partitioned monitoring of inflammation in central and peripheral airways. Different mathematical models are used to estimate pulmonary NO dynamics in asthma with variable results and limitations. We aimed to establish a protocol for extended NO analysis in patients with differing asthma severity. METHODS: Forty patients with stable asthma and 25 matched control subjects were recruited. Exhaled NO was measured at constant flow rates between 10 and 300 mL/s. Twelve controls performed NO measurements weekly for 4 weeks. RESULTS: The proportions of patients with technically acceptable measurements at 10-30-50-100-150-200-250-300 mL/s exhalation flow rates were 8-58-100-98-98-95-90-80%, respectively. Alveolar NO (CANO) and total flux of NO in the conducting airways (JawNO) were calculated with the linear method from NO values measured at 100-150-200-250 mL/s exhalation flows. The mean intrasubject bias for JawNO and CANO in controls was 0.16 nL/s and 0.85 ppb, respectively. Both JawNO (1.31/0.83-2.97/vs. 0.70/0.54-0.87/nL/s, p < 0.001) and CANO (4.08/2.63-7.16/vs. 2.42/1.83-2.89/ppb, p < 0.001) were increased in patients with asthma compared to controls. In patients, CANO correlated with RV/TLC (r = 0.58, p < 0.001), FEF25-75% (p = 0.02, r = -0.36) and DL,CO (r = -0.46, p = 0.004). JawNO was not related to lung function parameters. CONCLUSIONS: Calculation of alveolar NO concentration with the linear method from values obtained at medium flow rates (100-250 mL/s) is feasible even in asthmatic patients with severe airflow limitation and may provide information on small airways dysfunction in asthma.

Association Between Serum Lipid Profile and Obstructive Respiratory Events During REM and Non-REM Sleep.

PURPOSE: Obstructive sleep apnoea (OSA) represents a risk for dyslipidaemia. Obstructive respiratory events during rapid eye movement (REM) sleep are more strongly related to the development of hypertension and diabetes than in non-REM. However, the relationship between sleep phases and serum lipid profile is unclear. We aimed to analyse the relationship between obstructive respiratory events in REM and non-REM sleep as well as serum lipid profile. METHODS: Polysomnography was performed in 94 adult subjects who did not take any lipid-modifying medications. Fasting venous blood sample was taken the following morning for total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, lipoprotein(a), apoprotein A1 (ApoA1) and for apoprotein B (ApoB) measurements. Lipid profiles were correlated with apnoea-hypopnoea index (AHI) during REM (AHIREM) and non-REM (AHINREM) stages in all subjects. In addition, lipid profiles were compared between REM-dependent OSA patients (AHIREM ≥ 5/h, but AHINREM < 5/h) and control subjects (both AHIREM and AHINREM < 5/h). RESULTS: AHIREM correlated only with triglyceride concentrations (p = 0.04, Spearman's rho, ρ = 0.21). In contrast, there was a significant association between AHINREM and triglyceride (p = 0.02, ρ = 0.23), ApoB (p = 0.03, ρ = 0.21), HDL-C (p < 0.01, ρ = - 0.32) as well as ApoA1 levels (p = 0.04, ρ = - 0.21). However, these correlations were not present after adjustment for BMI (all p > 0.05). There was no difference in the lipid profile of REM-dependent OSA subjects and healthy controls (p > 0.05). CONCLUSIONS: Altered serum lipid profile is equally associated with a disturbed REM and non-REM sleep in OSA. Obesity must be considered as a strong covariate when interpreting lipid data in sleep apnoea.

Complement system activation in obstructive sleep apnea.

The complement system may play a role in the systemic inflammation characterising obstructive sleep apnea; however, this has not been investigated before. We aimed to study the involvement of effector complement elements in obstructive sleep apnea, namely C3a, C5a and SC5b-9. Venous blood was collected in 50 patients with obstructive sleep apnea and 26 control subjects in the evening and the following morning. Plasma complement proteins were analysed with ELISA. Complement factor levels were compared between the two groups and correlated with clinical variables. Plasma C3a concentration was elevated in obstructive sleep apnea both in the evening (84.1 [0-338.5] ng ml-1 ) and in the morning (85.5 [0-247.8] ng ml-1 ) compared with controls (30.3 [0-176.8] ng ml-1 and 36.3 [0-167.1] ng ml-1 , evening and morning, respectively, both p < 0.05). On the contrary, C5a and SC5b-9 levels were comparable between patients and controls at each time point (p > 0.05). There was no change in complement factors from evening to morning in either group (p > 0.05), except for C5a that decreased from evening to morning in obstructive sleep apnea (from 11.6 [1.6-47.4] ng ml-1 to 9.3 [0-46.4] ng ml-1 , p = 0.01). Elevated C3a levels were directly related to obstructive sleep apnea severity, and were significantly associated with male gender, weight, body mass index, hypertension, high C-reactive protein and low high-density lipoprotein cholesterol (p < 0.05). The complement system is activated in obstructive sleep apnea, which is correlated with disease severity. Our findings highlight the potential role of complement system in the pathophysiology of obstructive sleep apnea, thus facilitating further research.

Circulating Survivin Levels in Obstructive Sleep Apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA) is characterised by a low-grade systemic and airway inflammation; however, the regulatory mechanisms of inflammation are poorly explored. Survivin (Birc5) is an anti-apoptotic protein which inhibits Type 1 inflammation; however, this molecule has not been investigated in OSA. METHODS: Forty-five patients with OSA and 31 non-OSA control subjects were involved. Venous blood was collected for plasma survivin measurements before and after diagnostic overnight polysomnography. Plasma survivin levels were compared between the two groups and correlated to OSA severity and comorbidities. RESULTS: Plasma survivin levels were lower in OSA in the evening (27.6 ± 89.9 vs. 108.3 ± 161.2 pg/ml, p < 0.01) and in the morning (17.4 ± 48.6 vs. 36.4 ± 69.2 pg/ml, p = 0.02) compared to the control group. This OSA-related decrease was also present when only the non-obese patients were analysed. Significant indirect relationships were observed between plasma survivin levels and measures of OSA severity such as the apnoea-hypopnoea index (r = - 0.45) or oxygen desaturation index (r = - 0.40, both p < 0.01); however, when adjusting to BMI, these became insignificant (p > 0.05). Low plasma survivin concentrations were associated with high BMI (r = - 0.35), high CRP (r = - 0.31), low HDL cholesterol (r = 0.24) and high triglyceride levels (r = - 0.24, all p < 0.05). CONCLUSION: Plasma survivin levels are reduced in OSA, relate to disease severity, and are associated with high CRP levels. This suggests an impaired immunoregulation in this disorder which needs to be studied in further detail.

Overnight Changes in Lung Function of Obese Patients with Obstructive Sleep Apnoea.

PURPOSE: Obstructive sleep apnoea (OSA) is a prevalent disorder, characterised by collapse of the upper airways during sleep. The impact of sleep-disordered breathing on pulmonary function indices is however currently not well described. The aim of the study was to evaluate diurnal change in lung function indices in a cohort of patients with OSA and relate pulmonary function changes to disease severity. METHODS: 42 patients with OSA and 73 healthy control subjects participated in the study. Asthma and COPD were excluded in all volunteers following a clinical and spirometric assessment. Spirometry was then performed in all subjects in the evening and the morning following a polysomnography study. RESULTS: There was no difference in evening or morning FEV1 or FVC between patients and control subjects (p > 0.05). Neither FEV1 nor FVC changed in control subjects overnight (p > 0.05). In contrast, FEV1 significantly increased from evening (2.18/1.54-4.46/L) to morning measurement (2.26/1.42-4.63/L) in OSA without any change in FVC. The FEV1 increase in OSA was related to male gender, obesity and the lack of treatment with statins or ß-blockers (all p < 0.05). A tendency for a direct correlation was apparent between overnight FEV1 change and RDI (p = 0.05, r = 0.30). CONCLUSIONS: Diurnal variations in spirometric indices occur in patients with OSA and FEV1 appears to increase in subjects with OSA overnight. These changes occur in the absence of change in FVC and are directly related to the severity of OSA. These findings dictate a need to consider time of lung function measurement.

Diurnal variation of circulating microvesicles is associated with the severity of obstructive sleep apnoea.

PURPOSE: Microvesicles (MVs) have been implicated in the pathomechanism of obstructive sleep apnoea (OSA); however, the results are inconsistent, possibly due to an unrevealed temporal variation in circulating MV levels. We aimed to investigate the diurnal changes of MV fractions in OSA. METHODS: Peripheral blood was taken from 18 patients with OSA and 9 healthy subjects at different time points (11:00, 17:00, 21:00, 01:30 and 06:00). Samplings were repeated in nine OSA patients after 2 months of continuous positive airway pressure (CPAP) therapy. CD41+, CD62P+, glycophorin A+ and Annexin V+ MVs were determined with flow cytometry. Areas under the MV concentrations-time curves (AUC) were calculated and correlated with the severity of OSA. RESULTS: A significant diurnal variability of plasma CD41+ and Annexin V+ MVs was observed only in OSA with a marked peak at 17:00. There was a direct correlation between CD41+ MV AUCs and the severity of OSA. CPAP treatment reduced diurnal variability in both CD41+ and Annexin V+ MV levels. CONCLUSIONS: The relationship between the diurnal variability of CD41+ MVs and disease severity as well as the effect of CPAP treatment on MV levels support the role of MVs in the pathophysiology of OSA. More importantly, considering the significant diurnal variation in circulating MV levels, introduction of strict protocols for blood sampling is required for MV measurements.

NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD.

Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smoke-induced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39.Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema.Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage.

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation.

Sphingolipids are involved in the pathogenesis of inflammatory diseases. The central molecule is ceramide, which can be converted into ceramide-1-phosphate (C1P). Although C1P can exert anti- and pro-inflammatory effects, its influence on cigarette smoke (CS)-induced lung inflammation is unknown. We aimed to clarify the role of C1P in the pathogenesis of CS-triggered pulmonary inflammation and emphysema in humans and mice. The effects of C1P were addressed on CS-induced lung inflammation in C57BL/6 mice, CS extract-triggered activation of human airway epithelial cells (AECs) and neutrophils from patients with chronic obstructive pulmonary disease. Differential cell counts in bronchoalveolar lavage fluid were determined by flow cytometry and pro-inflammatory cytokines were measured by ELISA. Expression and DNA binding of nuclear factor (NF)-κB and neutral sphingomyelinase (nSMase) were quantified by PCR, electrophoretic mobility shift and fluorometric assays. C1P reduced CS-induced acute and chronic lung inflammation and development of emphysema in mice, which was associated with a reduction in nSMase and NF-κB activity in the lungs. nSMase activity in human serum correlated negatively with forced expiratory volume in 1 s % predicted. In human AECs and neutrophils, C1P inhibited CS-induced activation of NF-κB and nSMase, and reduced pro-inflammatory cytokine release. Our results suggest that C1P is a potential target for anti-inflammatory treatment in CS-induced lung inflammation.

Exhaled Breath Condensate pH in Lung Cancer, the Impact of Clinical Factors.

PURPOSE: Lung cancer may be associated with airway acidification due to enhanced airway inflammation and oxidative stress. Exhaled breath condensate (EBC) pH is a non-invasive indicator of airway acidity; however, it is still unclear how EBC pH changes in lung cancer. The aim of the study was to investigate EBC pH in lung cancer together with clinical variables. METHODS: Thirty-five patients with lung cancer and 37 control subjects (21 patients with stable COPD and 16 non-COPD smokers) were enrolled. EBC was collected for pH, which was determined with the argon-purging method, compared among the groups and correlated with clinical variables of patients with lung cancer. RESULTS: No difference was found in EBC pH between patients with lung cancer and control subjects. However, endobronchial tumour localisation, squamous-cell carcinoma subtype and gastro-oesophageal reflux were associated with low EBC pH values. No relationship was observed between EBC pH and the presence of COPD, lung function variables or smoking history. CONCLUSIONS: Although, EBC pH is unchanged in lung cancer, lower EBC pH values are associated with distinct phenotypes. Our findings could facilitate further research on airway acidity in lung cancer.

Evening and morning exhaled volatile compound patterns are different in obstructive sleep apnoea assessed with electronic nose.

PURPOSE: Electronic noses represent a technique for the measurement of exhaled breath volatile compound pattern which can discriminate patients with obstructive sleep apnoea (OSA) from control subjects. Although overnight changes in circulating biomarkers were reported, this effect on the exhaled volatile compound pattern has not been studied before. We aimed to compare breath patterns in the evening and in the morning in patients with OSA and to study the ability of the electronic nose to distinguish patients from controls based on these exhaled volatile patterns. METHODS: Exhaled breath volatile compound pattern was measured before and after night in 26 patients with suspected sleep-disordered breathing (53 ± 15 years) who underwent polysomnography and in ten control subjects (37 ± 15 years), by whom sleep-disordered breathing was excluded with a home apnoea screening device. Breath measurements were also performed in the morning in 26 healthy, non-smoking age-matched controls (48 ± 10 years) with no complaints about disturbed sleep. Exhaled volatile compound pattern was processed with a Cyranose 320 electronic nose, and principal component analysis was used for statistical analysis. RESULTS: Exhaled volatile compound patterns recorded in the evening and in the morning were different in patients with OSA (p = 0.01) but not in non-OSA habitual snorers (p = 0.49) or in control subjects (p = 0.23). The electronic nose distinguished patients with OSA from control subjects based on the breath samples collected in the morning (p < 0.001, classification accuracy 77 %) but not in the evening (p > 0.05). CONCLUSIONS: Evening and morning exhaled volatile compound patterns are different in OSA. This might affect the ability of electronic noses to identify this disorder. Overnight alterations in volatile substances need to be taken into account during exhaled breath measurements in OSA.

Modest genetic influence on bronchodilator response: a study in healthy twins.

AIM: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. METHODS: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 µg salbutamol). Univariate quantitative genetic modeling was performed. RESULTS: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P<0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1-adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). CONCLUSION: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

Genetic influence on capillary oxygen saturation: a twin study.

BACKGROUND: While heritability has been shown for daytime sleepiness, the heritability of daytime capillary oxygen saturation (SpO(2)) has not been described in detail. Our aim was to estimate the role of genes and environmental factors--both shared and unshared--in the variation of daytime SpO(2). METHODS: A total of 193 adult healthy twin pairs (138 monozygotic, 55 dizygotic) were recruited in Hungary and in the United States [age = 43.6 ± 15.6 years (mean ± SD)]. SpO(2) was measured by pulse oximetry. Univariate quantitative genetic modeling was performed to decompose the phenotypic variance of the considered parameter into heritability (A), shared (C), and unshared (E) environmental effects. RESULTS: SpO(2) twin correlation in monozygotic twins was stronger than in dizygotic twins (0.30 and -0.15, respectively, p < 0.05). Age-, sex-, country-, and body mass index-adjusted genetic effects accounted for 26 % (95 % CI 10, 45 %) of the variance of SpO(2), and the unshared environmental component explained the remaining 74 % (95 % CI 59, 89 %). No shared environmental influence on SpO(2) was detected. The heritability of SpO(2) was not different between smokers and nonsmokers. CONCLUSION: In summary, individual differences in daytime SpO(2) are explained by genetic and unshared environmental effects. The strong unshared environmental influence highlights the role of prevention of known environmental risk factors.

[Epidemiological and treatment characteristics of patients with chronic obstructive pulmonary disease on maintenance inhaled therapy between 2011 and 2019 in Hungary]. / A krónikus obstruktív tüdobetegség miatt fenntartó inhalációs kezelésben részesült betegek epidemiológiai és terápiás jellemzoi 2011 és 2019 között Magyarországon.

Introduction: Morbidity and mortality due to chronic obstructive pulmonary disease (COPD) are on the rise worldwide. The cornerstone of treatment is maintenance inhaled therapy and the patients' good treatment adherence. Objective: To determine epidemiological and treatment characteristics of patients treated with COPD in Hungary. Methods: Using data from the National Health Insurance Fund, we recruited patients under maintenance inhaled therapy due to COPD between 2011 and 2019 (aged >40 years, who filled in at least one prescription of a maintenance inhaled drug for ICD (International Classification of Diseases) code J44, which was followed by two further prescriptions within 1 year). Data of patients were analysed every year after inclusion. Findings on age, sex, inhaled therapies, and the use of retard oral theophylline were compared among the years (chi2 test). Results: In total, 227,251 patients were included (2011­2019: 81,308­160,241 patients/year). In 2011, most patients were >70 years of age and males, while in 2019, most patients were 60­69 years old and females. The proportion of patients filling in a prescription for mono-bronchodilators or inhaled corticosteroids decreased in the observational period, while dual bronchodilators became available, and their use gradually increased. The adherence to maintenance inhaled therapies was good (>180 days/year) only in approximately half of the population (51.6% in 2019). The number of patients filling in prescriptions for oral theophylline did not decline in the observation period (32% in 2019). Discussion: Between 2011 and 2019, the number of COPD patients on maintenance inhaled therapy did not reach that of the registered patients. Adherence to maintenance inhaled treatment is inadequate in a significant portion of patients. The rate of patients taking oral theophylline is high. Conclusion: Improvement of adherence to maintenance inhaled therapies is essential for a better prognosis of COPD in Hungary. Orv Hetil. 2024; 165(9): 338­345.

Platelet count and platelet-to-lymphocyte ratio at the onset of a severe COPD exacerbation are unrelated to the time till the next moderate or severe relapse.

PURPOSE: Acute exacerbations (AE) are severe complications of chronic obstructive pulmonary disease (COPD); however, the need for biomarkers which predict them is still unmet. High platelet count (PLC) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in patients with COPD. We investigated if PLC and PLR at the onset of a severe AE could predict the time of the next relapse. METHODS: In a prospective observational cohort study, data of 152 patients hospitalized with AECOPD were collected, and patients were divided into PLC-low (<239 â€‹× â€‹109/L, n â€‹= â€‹51), PLC-medium (239-297 â€‹× â€‹109/L, n â€‹= â€‹51) and PLC-high (>297 â€‹× â€‹109/L, n â€‹= â€‹50) or PLR-low (<147, N â€‹= â€‹51), PLR-medium (147-295, n â€‹= â€‹51) and PLR high (>295, n â€‹= â€‹50) groups based on PLC and PLR tertiles using admission laboratory results. Clinical characteristics and the time to the next severe or moderate AE within 52 weeks were compared among subgroups using log-rank test. RESULTS: PLC and PLR tertiles did not differ in clinical characteristics or the time till the next AE (p â€‹> â€‹0.05). PLC and PLR showed a direct weak correlation to neutrophil count (Pearson r â€‹= â€‹0.26, p â€‹< â€‹0.01 and r â€‹= â€‹0.20, p â€‹= â€‹0.01) and PLC also demonstrated a weak relationship to white blood cell counts (Pearson r â€‹= â€‹0.29, p â€‹< â€‹0.001). However, PLR presented an inverse relationship to monocyte and eosinophil counts (r â€‹= â€‹-0.32, p â€‹< â€‹0.001 and r â€‹= â€‹-0.17, p â€‹= â€‹0.03). CONCLUSION: PLC and PLR do not predict the time till the next relapse; however, they may reflect on neutrophilic inflammatory response during an exacerbation of COPD.

Assessment of bronchodilator responsiveness to salbutamol or ipratropium using different criteria in treatment-naïve patients with asthma and COPD.

Background: The criteria for significant bronchodilator responsiveness (BDR) were published in 2005 by the European Respiratory Society/American Thoracic Society, which were revised in 2021, however, data on the agreement between these two recommendations in untreated patients with airflow limitation are missing. Aims: We aimed to study BDR to salbutamol (SABA) or ipratropium bromide (SAMA) in patients with suspected bronchial asthma or COPD at initial clinical presentation using the 2005 and 2021 criteria and explore clinical factors associated with BDR+. Methods: Symptomatic, treatment-naïve patients with expiratory airflow limitation (n = 105, 57 men, age (mean ± standard deviation): 65 ± 10 years) underwent BDR testing with 400 mcg salbutamol (day 1) or 80 mcg ipratropium bromide (day 2) and BDR was measured after 15 and 30 minutes. Clinical factors with risk for BDR+ were assessed with binomial logistic regression analysis. Results: We found a good agreement between the number of 2005-BDR+ and 2021-BDR+ patients at 15 and 30 minutes post-salbutamol and post-ipratropium (88.6-94.8%). More patients showed BDR+ after 30 minutes than following 15 minutes using either criterion. When results at 30 minutes are considered, the number of patients with 2005-BDR+ (82%) was higher than that of 2021-BDR+ (75%), with the proportion of SAMA+ patients being higher than that of SABA+ (2005: 70% vs. 49%, Fisher exact p < 0.01; 2021: 64% vs. 41%, p = 0.001). 2005-BDR+ and 2021-BDR+ to SABA were associated with decreasing pre-BD FEV1% predicted and the presence of cough. More patients with asthma were in the SABA+ group compared to the SAMA+ group (2005: 71% vs. 53%, Fischer exact p = 0.04; 2021: 77% vs. 52%, p = 0.02). Conclusions: Fewer patients show BDR+ according to the 2021 criteria in comparison with the 2005 recommendations, and protocols for BDR testing may consider the assessment of response to both SABA and SAMA after 30 minutes.

Changes in exhaled breath condensate pH in healthy and asthmatic pregnant women.

OBJECTIVE: Asthma is a common chronic disease complicating pregnancy with a risk for perinatal complications. Control of airway inflammation in the asthmatic pregnancy improves pregnancy outcomes. Our aim was to evaluate pH of exhaled breath condensate (EBC), a non-invasive method for the assessment of asthmatic airway inflammation, in healthy and asthmatic pregnancies. DESIGN: Cross-sectional study. SETTING: Hungarian university clinics. POPULATION: Seventeen healthy pregnant women, 21 asthmatic pregnant women, 23 healthy non-pregnant women and 22 asthmatic non-pregnant women. METHODS: EBC samples were collected using a portable condenser, EBC pH was measured after argon deaeration. MAIN OUTCOME MEASURE: EBC pH. RESULTS: EBC pH (mean ± SD) of healthy non-pregnant and asthmatic non-pregnant women was similar (7.75 ± 0.27 vs. 7.54 ± 0.57; p = 0.118), probably indicating an optimal control of airway inflammation in asthmatic women. On the other hand, EBC pH was higher in healthy pregnant women compared with healthy non-pregnant women (8.02 ± 0.43 vs. 7.75 ± 0.27; p = 0.017). Higher EBC pH accompanying healthy pregnancy was absent in asthmatic pregnant patients whose EBC pH was lower (7.65 ± 0.38) than that of healthy pregnant women (p = 0.006), and it was similar to that in asthmatic and healthy non-pregnant women (p = 0.470 and p = 0.300, respectively). The EBC pH in asthmatic pregnant women correlated positively with birthweight (r = 0.49, p = 0.047) and negatively with forced vital capacity (r = 0.45, p = 0.039). EBC pH was not related to blood pH. CONCLUSIONS: EBC pH is higher in healthy pregnant women but not in asthmatic pregnant women compared with data from healthy non-pregnant women, indicating that oxidative inflammatory processes induced by asthma may compromise the regulatory mechanisms causing alkaline pH in the airways during pregnancy.