Predictors of excessive short-acting ß2-agonist use and asthma exacerbations: a retrospective analysis of a Polish prescription database.

Introduction: Despite being linked to unfavourable outcomes, short-acting ß2-agonists (SABAs) are still overused by a substantial proportion of patients with asthma. Aim: To analyse the prevalence and predictors of SABA overuse and exacerbations in patients with asthma in a nationwide database of prescription purchase records. Material and methods: The prevalence of excessive SABA use (≥ 12 canisters) and overuse (≥ 3 canisters) was analysed among patients aged 18-64 years who purchased asthma medications in 2018. Predictors of excessive SABA use and SABA overuse were examined by quasi-Poisson regression. Negative binomial regression was used to study the association of excessive SABA use or overuse to the risk of asthma exacerbation defined as a prescription for oral corticosteroids. Results: Of 91,763 patients with asthma, 42,189 (46%) were SABA users (mean age, 47 years; 58% female). Among them, 34% purchased ≥ 3 SABA canisters, and 6% purchased ≥ 12 canisters. The risk (risk ratio, 95% CI) of excessive SABA use was lower in patients with concomitant prescriptions for inhaled corticosteroids (0.41, 0.34-0.48) or inhaled corticosteroids and long-acting ß2-agonists (0.52, 0.47-0.56), women (0.63, 0.58-0.68), and those in secondary care (0.60, 0.44-0.66); older age was associated with a higher risk of excessive SABA use (1.06, 1.03-1.10). Excessive SABA use was the strongest predictor of asthma exacerbations among all patients (3.24, 2.84-3.70) and in those with ≥ 1 exacerbation (1.60, 1.50-1.71). Conclusions: Excessive SABA use is highly prevalent in asthma management, is associated with lack of prescriptions for inhaled corticosteroids, and substantially increases the exacerbation risk.

Airway inflammation in patients with chronic non-asthmatic cough.

INTRODUCTION: Chronic non-asthmatic cough (CC) is a clinical challenge and underlying pathophysiological mechanisms remain still not completely understood. One of the most common comorbidities in CC is gastro-oesophageal reflux disease (GORD). Airway epithelium damage can contribute to airway inflammation in CC. AIMS: We studied airway inflammation in patients with CC compared to healthy controls. Patients with GORD were treated with proton pump inhibitors (PPI) and cough response to PPI was evaluated. PATIENTS AND METHODS: Sputum was induced in 41 adults with CC and 20 healthy non-smokers who were age and sex matched. We compared sputum differential cell count by cytospin and cytokine and chemokine production at the mRNA and/or protein levels by real-time (RT)-PCR and cytokine bead array (CBA), between patients with CC and healthy subjects. Furthermore we studied airway inflammation in patients with different comorbidities. RESULTS: No differences in sputum differential cell counts were observed between patients with CC and healthy subjects. Sputum monocyte chemoattractant protein-1 (MCP-1) protein levels were significantly higher in patients when compared to controls. Thymic stromal lymphopoietin (TSLP) mRNA was significantly more often expressed in sputum of patients with CC than from healthy controls. Sputum transforming growth factor (TGF)-ß levels did not differ between patients and controls, but were significantly lower in the PPI responders compared to the non-responders; p=0.047. There is no evidence for impaired T helper cell (Th)1/Th2/Th17 balance in CC. Patients with reflux oesophagitis (RO) have significantly more sputum eosinophils than patients without RO. CONCLUSIONS: CC is a condition presenting with different disease phenotypes. High sputum MCP-1 levels are present in a large group of patients with CC and a majority of these patients with CC have increased sputum TSLP levels, most likely produced by damaged airway epithelial cells.

The role of the novel adipokines vaspin and omentin in chronic inflammatory diseases.

Obesity is a disease of epidemic proportions in many countries around the world. White adipose tissue is an active endocrine organ; therefore, its excess results in chronic and systemic inflammation. This inflammation is caused and maintained mostly by adipokines secreted by adipose tissue cells, mainly adipocytes and macrophages. The relatively newly discovered adipokines comprise vaspin and omentin. Their concentration in the blood, tissues, or bronchial secretion varies depending on the amount of adipose tissue and other accompanying factors, including comorbidities. The aim of this article is to demonstrate the usefulness of omentin and vaspin as biomarkers in inflammatory diseases. The Medline/PubMed database was used to search for information on obesity, inflammation, omentin, vaspin, and adipose tissue. Data from selected scientific studies, both original and review papers, are presented. Vaspin has been found to improve insulin sensitivity mainly in white adipose tissue. Omentin has an anti-inflammatory effect and, like vaspin, sensitizes tissues to insulin. The serum concentration and tissue expression of both adipokines are different in different inflammatory diseases. This review aims to present the biological functions of vaspin and omentin in the body and to indicate the possible use of these adipokines as disease markers in the future.

Efficacy of Sildenafil in Patients with Severe COVID-19 and Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is common in severe coronavirus disease 2019 (COVID-19) and worsens the prognosis. Sildenafil, a phosphodiesterase-5 inhibitor, is approved for PAH treatment but little is known about its efficacy in cases of severe COVID-19 with PAH. This study aimed to investigate the clinical efficacy of sildenafil in patients with severe COVID-19 and PAH. Intensive care unit (ICU) patients were randomly assigned to receive sildenafil or a placebo, with 75 participants in each group. Sildenafil was administered orally at 0.25 mg/kg t.i.d. for one week in a placebo-controlled, double-blind manner as an add-on therapy alongside the patient's routine treatment. The primary endpoint was one-week mortality, and the secondary endpoints were the one-week intubation rate and duration of ICU stay. The mortality rate was 4% vs. 13.3% (p = 0.078), the intubation rate was 8% and 18.7% (p = 0.09), and the length of ICU stay was 15 vs. 19 days (p < 0.001) for the sildenafil and placebo groups, respectively. If adjusted for PAH, sildenafil treatment significantly reduced mortality and intubation risks: OR = 0.21 (95% CI: 0.05-0.89) and OR = 0.26 (95% CI: 0.08-0.86), respectively. Sildenafil demonstrated some clinical efficacy in patients with severe COVID-19 and PAH and should be considered as an add-on therapy in these patients.

Impact of Alteplase on Mortality in Critically Ill Patients with COVID-19 and Pulmonary Embolism.

COVID-19 is an independent risk factor for pulmonary embolism (PE). Little is known about alteplase therapy in this patient group. A retrospective study analyzed 74 patients with PE and acute respiratory distress syndrome (ARDS) due to COVID-19 who were hospitalized in the intensive care unit in 2021. Patients with or without confirmed right heart thrombi (RHT) were treated with unfractionated heparin or alteplase. The mortality rate in patients with RHT treated with heparin was 100% compared to 37.9% and 55.2% in those treated with alteplase without RHT and alteplase with RHT, respectively. The risk of death in the alteplase group increased with delayed thrombolysis (p = 0.009, odds ratio (OR) = 1.73 95% CI (confidence interval) 1.14-2.62), increased D-dimer concentration (p = 0.02, OR = 1.43 95% CI 1.06-1.93), and decreased PaO2/FiO2 ratio (p = 0.001, OR = 0.56 95% CI 0.41-0.78). The receiver operating characteristic method determined that a 1-day delay in thrombolytic treatment, D-dimer concentration >5.844 mg/L, and PaO2/FiO2 <144 mmHg predicted a fatal outcome. The risk of death in patients with severe COVID-19 with ARDS and PE increases with higher D-dimer levels, decreased PaO2/FiO2, and delayed thrombolytic treatment. Thrombolysis seems to be treatment of choice in severe COVID-19 with PE and RHT. It should be carried out as soon as possible after the diagnosis is established.

[Application of metabolomic in COPD diagnosing]. / Metody metabolomiczne jako nowe narzedzie diagnostyki przewleklej obturacyjnej choroby pluc.

Chronic obstructive pulmonary disease (COPD) is very heterogeneous, with multiple phenotypes and hardly predictable clinical course. There are no clearly defined biomarkers measuring its progress and advancement. In the recent years, development of modem measurement techniques, first of all the nuclear magnetic resonance and mass spectrometry, allowed their widespread use in biological research. These techniques can analyze tens to several thousands of fine chemicals. Together with chemometric analysis create new diagnostic tool--metabolomics, which evaluates the biochemical processes in biological systems with an assessment of metabolome (the set of all metabolites--small molecules compounds MW < 1000 Da found in the biological material). This in turn makes possible to monitor the quantitative and qualitative changes in activity of the body's metabolism at the cellular level. Theoretically, this may allow to detect disturbances of homeostasis before the onset of clinical symptoms and yet measurable laboratory changes. The results, of the studies so far relatively few, studies with the use of metabolomic methods in COPD suggest that it might be possible to differentiate COPD from other diseases, as well as diagnosing patients with COPD, including disease stratification and severity. It is necessary to conduct further research in order to assess the sensitivity and specificity of these methods in COPD.

Lack of Difference in Tocilizumab Efficacy in the Treatment of Severe COVID-19 Caused by Different SARS-CoV-2 Variants.

Tocilizumab (TOC) is presumed to be an effective and safe treatment for severe COVID-19, but its usefulness has not been yet investigated for different SARS-CoV-2 variants. This study aimed to evaluate the influence of TOC on mortality in patients with severe COVID-19 caused by Delta and non-Delta SARS-CoV-2 variants. In a retrospective analysis, we compared the medical records of 78 and 224 patients with severe COVID-19 due to Delta and non-Delta variants, respectively. A total of 30 patients with Delta and 84 with non-Delta variants were treated with TOC in addition to standard therapy. There were no statistically significant differences in mortality rate when comparing Delta vs. non-Delta patients nor when comparing those treated with TOC vs. not treated with TOC in both variants. Using a logistic regression model, in the examined population as a whole, we found an increased (p < 0.05) risk of death as leukocyte and erythrocyte counts decreased and as procalcitonin increased. Increased procalcitonin was significant for mortality in the Delta group, while decreased IL-6, leukocytes, and platelets and increased fibrinogen and procalcitonin were significant in the non-Delta group. Tocilizumab efficacy in severe COVID-19 does not differ between Delta or non-Delta virus variants. The Delta variant of SARS-CoV-2 does not increase mortality when compared to other virus strains.

Exercise-induced anaphylaxis: an update on diagnosis and treatment.

Exercise-induced anaphylaxis (EIA) and food-dependent, exercise-induced anaphylaxis (FDEIA) are rare but potentially life-threatening clinical syndromes in which association with exercise is crucial. The range of triggering physical activities is broad, including as mild an effort as a stroll. EIA is not fully repeatable (ie, the same exercise may not always result in anaphylaxis in a given patient). In FDEIA, the combined ingestion of sensitizing food and exercise is necessary to precipitate symptoms. Clinical features and management do not differ significantly from other types of anaphylaxis. The pathophysiology of EIA and FDEIA is not fully understood. Different hypotheses concerning the possible influence of exercise on the development of anaphylactic symptoms are taken into consideration. These include increased gastrointestinal permeability, blood flow redistribution, and most likely increased osmolality. This article also describes current diagnostic and therapeutic possibilities, including changes in lifestyle and preventive properties of antiallergic drugs as well as acute treatment of these dangerous syndromes.

[Food-dependent exercise-induced anaphylaxis--current concepts in pathogenesis, diagnostics and treatment]. / Anafilaksja zalezna od pokarmu i indukowana wysilkiem-- wspólczesne poglady na patogeneze, diagnostyke i leczenie.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare syndrome, with symptoms caused by both ingestion of food allergen and physical exercise. The main purpose of this paper is to present current knowledge about FDEIA, focus on therapeutic possibilities, as well as to call attention to this uncommon and potentially life-threatening disease. The authors critically reviewed the data from available publications, including recent observations regarding pathomechanism, clinical history, severity-based classification of anaphylaxis symptoms, diagnostics and treatment options, including pharmacological prophylaxis.

Oxygen metabolism markers as predictors of mortality in severe COVID-19.

OBJECTIVE: To investigate the use of oxygen metabolism markers as predictors of mortality in patients with severe coronavirus disease 2019 (COVID-19). METHODS: A retrospective analysis was undertaken to compare the medical records of patients with severe COVID-19 (53 deceased patients and 50 survivors). The survivors were selected from 222 records using a random number generator. In addition, 28 individuals who considered themselves to be healthy and who had no history of serious illness were included in the study for comparison. Oxygen saturation in arterial blood, oxygen saturation in central venous blood (ScvO2), arterial partial pressure of oxygen (PaO2), respiratory index (PaO2/fraction of inspired oxygen), oxygen delivery, oxygen consumption (VO2) and oxygen extraction (O2ER) were compared in all participants. The optimal cut-off point for each oxygen metabolism marker in the prediction of mortality was determined based on the maximum value of the Youden Index in receiver operating characteristic curve analysis. RESULTS: Significant differences in all studied oxygen metabolism markers were found between survivors compared with deceased patients (p < 0.001). ScvO2, VO2 and O2ER [area under curve (AUC) 1.0] were the strongest predictors of mortality, and PaO2 was the weakest predictor of mortality (AUC 0.81). ScvO2 <29%, VO2 >124.6 ml/min and O2ER >30.2% were identified as predictors of mortality in patients with COVID-19. CONCLUSION: ScvO2, VO2 and O2ER are good predictors of mortality in critically ill patients with COVID-19.

Comparison of the Effect of Unfractionated Heparin and Enoxaparin Sodium at Different Doses on the Course of COVID-19-Associated Coagulopathy.

BACKGROUND: COVID-19-associated coagulopathy (CAC) exacerbates the course of coronavirus infection and contributes to increased mortality. Current recommendations for CAC treatment include the use of low-molecular weight heparins (LMWH) at prophylactic or therapeutic doses, as well as the use of unfractionated heparin (UFH). METHODS: A randomised, controlled trial enrolled 126 patients hospitalised in the intensive care unit with severe COVID-19 complicated by CAC. The effects of LMWH at preventive and therapeutic doses and UFH at therapeutic doses on mortality and intubation rates were compared. RESULTS: The number of intubations and deaths showed no significant difference depending on the anticoagulant therapy used. However, multivariate logistic regression models revealed an increased risk of intubation (p = 0.026, odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.15-9.59), and an increased risk of death (p = 0.046, OR = 3.01, 95% CI 1.02-8.90), for patients treated with LMWH at a prophylactic dose but not at a therapeutic dose as compared to patients treated with UFH when controlling for other risk factors. CONCLUSIONS: The use of unfractionated heparin in the treatment of COVID-19-associated coagulopathy seems to be more effective at reducing the risk of intubation and death than enoxaparin at prophylactic doses.

Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome.

BACKGROUND: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. METHODS: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. RESULTS: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25-0.99). CONCLUSIONS: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

The G/G genotype of transforming growth factor beta 1 (TGF-beta1) single nucleotide (+915G/C) polymorphism coincident with other host and environmental factors is associated with irreversible bronchoconstriction in asthmatics.

Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)-beta1 gene polymorphism despite established role that TGF-beta1 plays in airway remodelling. We tested TGF-beta1 single-nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case-control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00-19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF-beta1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.

The diagnostic usefulness of the basophil activation test (BAT) with annexin V in an allergy to Alternaria alternata.

BACKGROUND: The basophil activation test (BAT) is an effective diagnostic tool in mold allergy, which is still not sufficiently known. OBJECTIVES: The aim of our study was to assess the degree of annexin V binding to the surface of the basophil cell membrane after stimulation with anti-immunoglobulin E (anti-IgE) and Alternaria alternata allergenic extract. MATERIAL AND METHODS: Alternaria alternata allergic patients (n = 32) and healthy volunteers (n = 33) were evaluated using skin prick tests (SPT), quantification of specific IgE (sIgE) and the BAT. Basophil activation was detected as a percentage degree of annexin V binding to the surface of the basophil cell membrane. RESULTS: Receiver operating characteristic (ROC) curve analysis yielded a threshold value of 4.95% of activated basophils when the tested group and control group were studied, with a sensitivity and specificity of 100% (area under curve [AUC] = 1; p = 0.00000) for 100 SBU/mL Alternaria alternata allergen extract. The threshold value was 10.28% with a sensitivity of 93.8% and specificity of 100% (AUC = 0.98958; p = 0.00000) for 10 SBU/mL mold extract, and 9.37% with a sensitivity of 90.3% and specificity of 100% (AUC = 0.96307; p = 0.00000) for 1 SBU/mL Alternaria alternata allergen extract. The method was least efficacious in antiIgE stimulation, where the threshold value was 5.48% with a sensitivity of 90.6% and specificity of 30.3% (AUC = 0.46780; p = 0.67039). CONCLUSIONS: The BAT with annexin V and sIgE measurement against Alternaria alternata increase the capability of a diagnostic laboratory for detecting mold sensitization. Both methods may certainly replace SPT, which are currently routinely used in allergy diagnosis. Annexin V may be considered a new basophil activation marker with an efficacy comparable to that of CD63 or CD203c.

The use of magnesium in bronchial asthma: a new approach to an old problem.

Magnesium deficiency is a common electrolyte disorder in patients with acute severe asthma, but intracellular magnesium content better reflects its homeostasis than does its serum concentration. Magnesium takes part in many metabolic processes in the organism, including energy metabolism, protein and nucleic acid synthesis, cell cycle, the binding of substances to the plasma membrane, and maintenance of cytoskeletal and mitochondrial integrity. It also modulates ion transport and influences intracellular calcium concentration. Maintenance of the cells' transmembrane gradient depends on the presence of magnesium, and hypomagnesemia may result in an increase in neuromuscular cell excitability. Magnesium is a cation modulating the smooth muscle contractility of different tissues: hypomagnesemia causes their contraction and hypermagnesemia their relaxation. Suggestions of a positive influence of magnesium in the treatment of asthma exacerbation have been known for a long time, but research results differ. A single dose of intravenous magnesium sulfate given to patients with acute asthma exacerbation has been shown to be safe, but its efficiency is still under discussion. According to the Global Initiative for Asthma GINA-2005, magnesium sulfate administration is not recommended for routine treatment, but it is permitted in patients with severe asthma exacerbation not responding to treatment (evidence category A). Recommendations of the British Thoracic Society allow one dose of magnesium sulfate to patients with acute severe asthma exacerbation and inadequate initial response to broncho-dilating inhalation treatment (evidence category A). Future investigations should help to establish the indications for magnesium use in the treatment of acute asthma exacerbations as well as the magnesium dose and the scheme of its administration.

[The variability of peak inspiratory flow (PIF) on valves imitating dry powder inhalers resistance during asthma and COPD exacerbations]. / Zmiennosc szczytowego przeplywu wdechowego (PIF)na zastawkach imitujacych opory inhalatorów proszkowychw zaostrzeniu astmy i POChP.

INTRODUCTION: Drugs used in asthma or COPD exacerbation are delivered to the lungs by inhalation. This is facilitated, among other factors, by the use of dry powder inhalers (DPIs). Lung deposition from DPI depends predominantly on peak inspiratory flow (PIF). The aim of the study was to asses the variability of PIF generated by patients using different types of DPI inhalers during asthma or COPD exacerbation and to trace possible relationships between PIF value and some spirometric values. MATERIAL AND METHODS: There were 28 patient fulfilling inclusion criteria, among them 17 (4 women) were suffering from COPD and 11 (8 women) from asthma. Spirometry, PEF and PIF measurements were performed in the first and the last day of hospitalisation. Peek inspiratory flow was obtained using In-Check DIAL - a device which simulated airflow resistances equivalent to Turbuhaler, Diskus and Aeroliser respectively. RESULTS: The significant improvement in PIF was observed only in patients with COPD. There were no statistically significant correlations between PIF and both FEV1 and PEF except those in the first day of hospitalization in COPD patients (r = 0.66-0.81). Optimal PIF was achieved in all patients only with Diskus. CONCLUSIONS: Measurements of peek inspiratory flow are useful in choosing the most suitable DPI for patients with COPD and asthma exacerbations. We conclude that in those patients, PIF measurement should complement a standard spirometry.

[Status asthmaticus]. / Stan astmatyczny.

Status asthmaticus, the most severe form of asthma exacerbation, is a life-threatening condition. The mortality rate in status asthmaticus ranges from 3.5% to 8.3%. Therapeutic approach in acute severe asthma is based on oxygen supply, high doses of nebulised beta2-agonists and systemic corticosteroids administered intravenously or orally. Second line therapy is comprised of methyloxantines, nebulised cholinolitics and management of electrolytes and water balance. Status asthmaticus resulting in acute respiratory failure will often require invasive or non-invasive mechanical ventilation. Mortality in patients with asthma who require mechanical ventilation might exceed 20%. International guidelines for management of status asthmaticus have been published recently, but those recommendations often remain unknown. Thus there is an urgent need for elaboration of national standards on managing acute severe asthma and putting it into clinical practice. Status asthmaticus, especially a severe one, should be treated in a respiratory intermediate intensive care unit.

[TGF-beta1 gene polymorphism in chronic obstructive pulmonary disease]. / Polimorfizm genu TGF-beta1 w przewleklej obturacyjnej chorobie pluc.

Gene polymorphism is often responsible for occurrence of some chronic diseases. It has not been clarified, why only 15-20% of smokers suffer from chronic obstructive pulmonary disease (COPD). TGF-beta1 gene polymorphism has been postulated as one of possible genetic risk factors. The aim of our study was to evaluate TGF-beta1 gene polymorphism in codons 10 and 25 in COPD patients in comparison to healthy controls. Thirty six COPD patients and 60 healthy persons entered the study. The distribution of TGF-beta1 genotypes in codon 10 was as follows in COPD group: T/C--50%, T/T--25% and C/C--25% in control group: 45%, 42% and 13% respectively. The distribution of genotypes in codon 25 in COPD patients was: G/G 86% and G/C 14%, in control group 83% and 17% respectively. There were not statistically significant differences between evaluated groups with regard to both polymorphisms. Moreover, in group of 27 smokers without COPD the distribution of the analysed TGF-beta1 gene polymorphism was similar to that in COPD group. After adjustment to sex, age and smoking index, in the logistic regression model, we can not confirm the hypothesis that TGF-beta1 gene polymorphisms in codons 10 and 25 might be significant risk factors of COPD.

Fusion of the 1H NMR data of serum, urine and exhaled breath condensate in order to discriminate chronic obstructive pulmonary disease and obstructive sleep apnea syndrome.

Chronic obstructive pulmonary disease, COPD, affects the condition of the entire human organism and causes multiple comorbidities. Pathological lung changes lead to quantitative changes in the composition of the metabolites in different body fluids. The obstructive sleep apnea syndrome, OSAS, occurs in conjunction with chronic obstructive pulmonary disease in about 10-20 % of individuals who have COPD. Both conditions share the same comorbidities and this makes differentiating them difficult. The aim of this study was to investigate whether it is possible to diagnose a patient with either COPD or the OSA syndrome using a set of selected metabolites and to determine whether the metabolites that are present in one type of biofluid (serum, exhaled breath condensate or urine) or whether a combination of metabolites that are present in two biofluids or whether a set of metabolites that are present in all three biofluids are necessary to correctly diagnose a patient. A quantitative analysis of the metabolites in all three biofluid samples was performed using 1H NMR spectroscopy. A multivariate bootstrap approach that combines partial least squares regression with the variable importance in projection score (VIP-score) and selectivity ratio (SR) was adopted in order to construct discriminant diagnostic models for the groups of individuals with COPD and OSAS. A comparison study of all of the discriminant models that were constructed and validated showed that the discriminant partial least squares model using only ten urine metabolites (selected with the SR approach) has a specificity of 100 % and a sensitivity of 86.67 %. This model (AUCtest = 0.95) presented the best prediction performance. The main conclusion of this study is that urine metabolites, among the others, present the highest probability for correctly identifying patents with COPD and the lowest probability for an incorrect identification of the OSA syndrome as developed COPD. Another important conclusion is that the changes in the metabolite levels of exhaled breath condensates do not appear to be specific enough to differentiate between patients with COPD and OSAS.