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.

A Real-World Multicenter Retrospective Observational Study on Polish Experience with Nintedanib Therapy in Patients with Idiopathic Pulmonary Fibrosis: The PolExNIB Study.

Nintedanib is a disease-modifying agent licensed for the treatment of IPF. Data on Polish experience with nintedanib in IPF are lacking. The present study aimed to describe the safety and efficacy profiles of nintedanib in a large real-world cohort of Polish patients with IPF. This was a multicenter, retrospective, observational study of IPF patients treated with nintedanib between March 2018 and October 2021. Data collection included baseline clinical characteristics, results of pulmonary function tests (PFTs), and a six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), and treatment persistence were also retrieved. A total of 501 patients (70% male) with a median age of 70.9 years (IQR 65-75.7) were included in this study. Patients were followed on treatment for a median of 15 months (7-25.5). The majority of patients (66.7%) were treated with the full recommended dose of nintedanib and 33.3% of patients were treated with a reduced dose of a drug. Intermittent dose reductions or drug interruptions were needed in 20% of patients. Over up to 3 years of follow-up, pulmonary function remained largely stable with the minority experiencing disease progression. The most frequent ADRs included diarrhea (45.3%), decreased appetite (29.9%), abdominal discomfort (29.5%), weight loss (32.1%), nausea (20.8%), fatigue (19.2%), increased liver aminotransferases (15.4%), and vomiting (8.2%). A total of 203 patients (40.5%) discontinued nintedanib treatment due to diverse reasons including ADRs (10.2%), death (11.6%), disease progression (4.6%), patient's request (6.6%), and neoplastic disease (2.2%). This real-world study of a large cohort of Polish patients with IPF demonstrates that nintedanib therapy is safe, and is associated with acceptable tolerance and disease stabilization. These data support the findings of previously conducted clinical trials and observational studies on the safety and efficacy profiles of nintedanib in IPF.

Endobronchial Ultrasound is Useful in the Assessment of Bronchial Wall Changes Related to Bronchial Thermoplasty.

Background: Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe asthma leading to the clinical improvement, but morphologic changes of bronchial wall related to the procedure and predictors of a favorable response to BT remain uncertain. The aim of the study was to validate an endobronchial ultrasound (EBUS) in assessing the effectiveness of BT treatment. Methods: Patients with severe asthma who met the clinical criteria for BT were included. In all patients clinical data, ACT and AQLQ questionnaires, laboratory tests, pulmonary function tests and bronchoscopy with radial probe EBUS and bronchial biopsies were collected. BT was performed in patients with the thickest bronchial wall L2 layer representing ASM. These patients were evaluated before and after 12 months of follow-up. The relationship between baseline parameters and clinical response was explored. Results: Forty patients with severe asthma were enrolled to the study. All 11 patients qualified to BT successfully completed the 3 sessions of bronchoscopy. BT improved asthma control (P=0.006), quality of life (P=0.028) and decreased exacerbation rate (P=0.005). Eight of the 11 patients (72.7%) showed a clinically meaningful improvement. BT also led to a significant decrease in the thicknesses of bronchial wall layers in EBUS (L1 decreased from 0.183 to 0.173 mm, P=0.003; L2 from 0.207 to 0.185 mm, P = 0.003; and L3-5 from 0.969 to 0.886 mm, P=0.003). Median ASM mass decreased by 61.8% (P=0.002). However, there was no association between baseline patient characteristics and the magnitude of clinical improvement after BT. Conclusion: BT was associated with a significant decrease in the thickness of the bronchial wall layers measured by EBUS including L2 layer representing ASM and ASM mass reduction in bronchial biopsy. EBUS can assess bronchial structural changes related to BT; however, it did not predict the favorable clinical response to therapy.

Temporal changes of hemostatic activity in patients hospitalized for COVID-19: a prospective observational study.

INTRODUCTION: Hemostatic abnormalities play an important role in the pathogenesis of COVID­19 and are considered determinants of the patients' outcomes. Less is known about the dynamics of these abnormalities in a short­term observation. OBJECTIVES: The aim of the study was to evaluate hemostatic activity markers in patients hospitalized for COVID­19 depending on the severity of respiratory failure. PATIENTS AND METHODS: This was a prospective observational study enrolling adult patients hospitalized for COVID­19 in a tertiary center in Poland, from January to May 2021. Blood samples were drawn upon admission and 28 days after the admission to measure the markers of coagulation, fibrinolysis, and endothelial dysfunction, and to evaluate whether there are significant differences between these 2 time points. All analyses were performed in the entire cohort and after stratification into 3 groups depending on the degree of respiratory support. RESULTS: We recruited 245 patients at the median age of 63 years (interquartile range, 52-69), among whom 158 (64.5%) were men. The analysis of hemostatic markers on admission revealed that hypercoagulability, hypofibrinolysis, and endothelial dysfunction are related to the degree of respiratory support. We found significant differences between the admission and 28­day follow­up in all markers except for plasminogen activity. Interestingly, the markers of endothelial dysfunction remained the highest in the advanced respiratory support group after 28 days, while differences in the other markers diminished. CONCLUSION: Hemostatic abnormalities are significantly attenuated within a month after a hospital admission due to COVID­19. The initially observed association between severity of the disease and hemostatic derangements persists only for the markers of endotheliopathy.

Decreased protein C activity, lower ADAMTS13 antigen and free protein S levels accompanied by unchanged thrombin generation potential in hospitalized COVID-19 patients.

INTRODUCTION: COVID-19 is associated with an increased thromboembolic risk. However, the mechanisms triggering clot formation in those patients remain unknown. PATIENTS AND METHODS: In 118 adult Caucasian severe but non-critically ill COVID-19 patients (median age 58 years; 73 % men) and 46 controls, we analyzed in vitro plasma thrombin generation profile (calibrated automated thrombogram [CAT assay]) and investigated thrombophilia-related factors, such as protein C and antithrombin activity, free protein S level, presence of antiphospholipid antibodies and factor V Leiden R506Q and prothrombin G20210A mutations. We also measured circulating von Willebrand factor (vWF) antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antigen and activity. In patients, blood samples were collected on admission to the hospital before starting any therapy, including heparin. Finally, we examined the relationship between observed alterations and disease follow-up, such as thromboembolic complications. RESULTS: COVID-19 patients showed 17 % lower protein C activity, 22 % decreased free protein S levels, and a higher prevalence of positive results for IgM anticardiolipin antibodies. They also had 151 % increased vWF, and 27 % decreased ADAMTS13 antigens compared with controls (p < 0.001, all). On the contrary, thrombin generation potential was similar to controls. In the follow-up, pulmonary embolism (PE) occurred in thirteen (11 %) patients. They were characterized by a 55 % elevated D-dimer (p = 0.04) and 2.7-fold higher troponin I (p = 0.002) during hospitalization and 29 % shorter time to thrombin peak in CAT assay (p = 0.009) compared to patients without PE. CONCLUSIONS: In COVID-19, we documented prothrombotic abnormalities of peripheral blood. PE was characterized by more dynamic thrombin generation growth in CAT assay performed on admittance to the hospital.

Association of discharge policy with the length of hospital stay among patients with coronavirus disease 2019: a cross-sectional study.

AIM: To assess the association between discharge policy and hospital stay length, and to evaluate the factors related to duration of viral clearance among patients with coronavirus disease 2019 (COVID-19). METHODS: This cross-sectional study enrolled consecutive patients aged ≥18 years with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction test who were admitted to hospital. The participants were divided into the test-based (TB) policy group or symptom-based (SB) group depending on the policy valid at their hospital discharge. Multivariable analyses were performed to assess the factors related to the duration of hospital stay and viral clearance. RESULTS: The study involved 305 patients (66.6% men). The mean age was 60.9 (15.2) years. TB and SB policy groups consisted of 145 (47.5%) and 160 patients (52.5%), respectively. The TB group had significantly longer duration of hospital stay (21.0 vs 16.0, P=0.003). In multivariable analysis, SB policy was associated with significantly shorter hospital stay (ß-coefficient -5.87, 95% confidence interval [CI] -9.78 to -1.96, P=0.003). Longer viral clearance was associated with older age (ß-coefficient 0.33, 95% CI 0.15 to 0.51, P<0.001) and history of cough in the pre-hospital phase of the disease (5.96, 95% CI 0.64 to 11.29, P = 0.028). CONCLUSION: SB discharge policy is preferable in the context of limited resources during the COVID-19 pandemic.

Discrimination between NSIP- and IPF-Derived Fibroblasts Based on Multi-Parameter Characterization of Their Growth, Morphology and Physic-Chemical Properties.

BACKGROUND: The aim of the research presented here was to find a set of parameters enabling discrimination between three types of fibroblasts, i.e., healthy ones and those derived from two disorders mimicking each other: idiopathic pulmonary fibrosis (IPF), and nonspecific interstitial pneumonia (NSIP). METHODS: The morphology and growth of cells were traced using fluorescence microscopy and analyzed quantitatively using cell proliferation and substrate cytotoxicity indices. The viability of cells was recorded using MTS assays, and their stiffness was examined using atomic force microscopy (AFM) working in force spectroscopy (FS) mode. To enhance any possible difference in the examined parameters, experiments were performed with cells cultured on substrates of different elasticities. Moreover, the chemical composition of cells was determined using time-of-flight secondary ion mass spectrometry (ToF-SIMS), combined with sophisticated analytical tools, i.e., Multivariate Curve Resolution (MCR) and Principal Component Analysis (PCA). RESULTS: The obtained results demonstrate that discrimination between cell lines derived from healthy and diseased patients is possible based on the analysis of the growth of cells, as well as their physical and chemical properties. In turn, the comparative analysis of the cellular response to altered stiffness of the substrates enables the identification of each cell line, including distinguishing between IPF- and NSIP-derived fibroblasts.

Assessment of Airway Remodeling Using Endobronchial Ultrasound in Asthma-COPD Overlap.

PURPOSE: The aim of this study was to evaluate the structural changes of the airways using the endobronchial ultrasound (EBUS) in ACO patients compared to severe asthma and COPD patients. PATIENTS AND METHODS: The study included 17 patients with ACO, 17 patients with COPD and 33 patients with severe asthma. Detailed clinical data were obtained from all participants. Basic laboratory tests were performed, including measurement of eosinophil counts in blood and serum immunoglobulin E (IgE) concentrations. All patients underwent spirometry and bronchoscopy with EBUS (a 20­MHz ultrasound probe) to measure the total thicknesses of the bronchial walls and their particular layers in segmental bronchi of the right lower lobe. EBUS allows to distinguish five layers of the bronchial wall. Layer 1 (L1) and layer 2 (L2) were analyzed separately, while the outer layers (layers 3-5 [L3-5]) that correspond to cartilage were assessed together. RESULTS: In patients with ACO the thicknesses of the L1 and L2 layers, which are mainly responsible for remodeling, were significantly greater than in patients with COPD and significantly smaller than in patients with severe asthma (median L1= 0.17 mm vs 0.16 mm vs 0.18 mm, p<0.001; median L2= 0.18 mm vs 0.17 mm vs 0.20 mm, p<0.001, respectively). The thicknesses of the total bronchial walls (L1+L2+L3-5) and L3-5 were significantly smaller in ACO and COPD patients compared to asthma patients (median L1+L2+L3-5= 1.2 mm vs 1.14 mm vs 1.31 mm, p<0.001; median L3-5= 0.85 mm vs, 0.81 mm vs 0.92 mm, p=0.001, respectively). CONCLUSION: The process of structural changes in the airways assessed by EBUS is more advanced in individuals with ACO compared to patients with COPD, and less pronounced compared to patients with severe asthma. It seems that EBUS may provide useful information about differences in airway remodeling between ACO, COPD and severe asthma.

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.

A clinical profile and factors associated with severity of the disease among Polish patients hospitalized due to COVID-19 - an observational study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is one of the greatest clinical challenges of the last decades. Clinical factors associated with severity of the disease remain unclear. The aim of the study was to characterize Polish patients hospitalized due to COVID-19 and to evaluate potential prognostic factors of severe course of the disease. MATERIAL AND METHODS: An observational study was conducted from March to July 2020 in the Pulmonology and Allergology Department of the University Hospital in Kraków, Poland. Consecutive patients with confirmed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection were enrolled, and data about past medical history, signs and symptoms, laboratory results, imaging studies results, in-hospital management and outcomes was prospectively gathered. RESULTS: The study sample comprised 100 patients at the mean age of 59.2 (SD 16.1) years among whom 63 (63.0%) were male. Among them 10 (10.0%) died, 47 (47%) presented respiratory failure, 15 (15.0%) were transferred to the intensive care unit, 17 (17.0%) developed acute kidney injury, 7 (7.0%) had sepsis and 10 (10.0%) were diagnosed with pulmonary embolism. Multivariable analysis revealed age (OR 1.1; 95% CI 1.01-1.15), body mass index (BMI; OR 1.24; 95% CI 1.01-1.53), modified early warning score (MEWS; OR 3.95; 95% CI 1.48-12), the highest d-dimer value (OR 1.73; 95% CI 1.03-2.9) and lactate dehydrogenase (LDH; OR 1.16; 95% CI 1.03-1.3) to be associated with severe course of COVID-19. CONCLUSION: This observational study showed that almost half of hospitalized patients with COVID-19 developed respiratory failure in the course of the disease. Increasing age, BMI, MEWS, d-dimer value and LDH concentration were associated with the severity of COVID-19.

The influence of self-assessment of asthma control on the Asthma Control Test outcome.

OBJECTIVE: The Asthma Control Test (ACT) consists of five items, one of which is self-assessment of asthma control. The goal of this study was to compare the responses to the first four ACT items with the response to the fifth item and determine whether this response affects the final ACT score. METHODS: Adult asthmatics (n = 417) were recruited from a specialty asthma center in Poland. Clinical data were collected by questionnaire. Spirometry and skin prick tests were performed for clinical evaluation. Asthma control was assessed through the ACT. The cutoff point for uncontrolled asthma was <20 points. RESULTS: Asthma was uncontrolled in 42.5% of patients. Based upon scores of the first four ACT items, three clusters of patients were identified. Cluster 1 comprised very well-controlled asthmatics [mean (sd) ACT total score 24.7 (0.7)]. Cluster 2 included both controlled and uncontrolled asthmatics [ACT total score 20.1 (2.5)]. Cluster 3 comprised poorly controlled asthmatics [ACT total score 12.1 (2.9)]. Misjudgment of asthma control in the fifth ACT item had no impact on the ACT total score in clusters 1 and 3. In cluster 2, the response to this item caused misclassification in 10.2% of patients. CONCLUSIONS: In patients with either very well or very poorly controlled asthma, the response to the fifth ACT item did not alter the assignment into the appropriate asthma control group. Only in a small group of patients with a total ACT score of approximately 20 points did the asthma group classification result in either controlled or uncontrolled.

Effect of Substrate Stiffness on Physicochemical Properties of Normal and Fibrotic Lung Fibroblasts.

The presented research aims to verify whether physicochemical properties of lung fibroblasts, modified by substrate stiffness, can be used to discriminate between normal and fibrotic cells from idiopathic pulmonary fibrosis (IPF). The impact of polydimethylsiloxane (PDMS) substrate stiffness on the physicochemical properties of normal (LL24) and IPF-derived lung fibroblasts (LL97A) was examined in detail. The growth and elasticity of cells were assessed using fluorescence microscopy and atomic force microscopy working in force spectroscopy mode, respectively. The number of fibroblasts, as well as their shape and the arrangement, strongly depends on the mechanical properties of the substrate. Moreover, normal fibroblasts remain more rigid as compared to their fibrotic counterparts, which may indicate the impairments of IPF-derived fibroblasts induced by the fibrosis process. The chemical properties of normal and IPF-derived lung fibroblasts inspected using time-of-flight secondary ion mass spectrometry, and analyzed complexly with principal component analysis (PCA), show a significant difference in the distribution of cholesterol and phospholipids. Based on the observed distinctions between healthy and fibrotic cells, the mechanical properties of cells may serve as prospective diagnostic biomarkers enabling fast and reliable identification of idiopathic pulmonary fibrosis (IPF).

Evaluating the applicability of MESS (matrix exponential spatial specification) model to assess water quality using GIS technique in agricultural mountain catchment (Western Carpathian).

The formation of many sources of pollution in a short period of time is due to mountain soil erosion by water. One of the major mechanisms decisive in the intensification of such erosion is the loosening of soil material on the slope. Water quality studies show the impact of diversified spatial management and allow making the right decisions in environmental management in mountain areas with high variability of use and land cover. The research undertaken as part of the paper was carried out in order to determine the dependency between total suspended solids (TSS) and the physicochemical parameters of surface waters and the amount of soil losses in the use structure within the mountain catchment. The paper focused on the frequency of phenomena in time and the possibility of stopping the surface runoff on the slope and on the soil's susceptibility to water erosion. The dependencies between multipoint sampling and the concentration of material washed off the slope due to precipitation were verified with a multivariate analysis. Sampling took place in hydrometric sections, and during small floods, in the waterbed cross section. Research shows that such sampling is the basis for the calculation of the transported load, reflecting the average variation in concentration. The variation in the volume of the load from the individual parts of the catchment was assessed by the spatial autoregressive model. It was found that the use of river basin areas affects water chemistry. Water reservoirs are an important ecological barrier for the migration of nitrate nitrogen (N-NO3) and phosphate phosphorus (P-PO4), which is marked by changes in the growing season. Water along the sections of the river near the quarry with a high degree of sodding showed good quality condition. Despite significant differences between measurement sampling sites, high total dissolved solid (TDS) values were found in communities adjacent to forests and meadows. However, the highest electrical conductivity (EC) and TSS concentrations were found in the interface with cultivated areas. Biogenic indices showed variation depending on the way the adjacent areas were used. GIS linked spatial variables with the formation of water pollution. The analysis of spatial autoregression pointed to the impact of arable land. Moreover, the analysis of spatial autoregression with the MESS function designated a connection between agricultural land use and nitrite nitrogen (N-NO2), EC, TSS, and dissolved oxygen (DO). Graphical abstract ᅟ.

The utility of biomarkers in diagnosis of aspirin exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a distinct eosinophilic phenotype of severe asthma with accompanying chronic rhinosinusitis, nasal polyposis, and hypersensitivity to aspirin. Urinary 3-bromotyrosine (uBrTyr) is a noninvasive marker of eosinophil-catalyzed protein oxidation. The lack of in vitro diagnostic test makes the diagnosis of AERD difficult. We aimed to determine uBrTyr levels in patients with AERD (n = 240) and aspirin-tolerant asthma (ATA) (n = 226) and to assess whether its addition to urinary leukotriene E4 (uLTE4) levels and blood eosinophilia can improve the prediction of AERD diagnosis. METHODS: Clinical data, spirometry and blood eosinophilis were evaluated. UBrTyr and uLTE4 levels were measured in urine by HPLC and ELISA, respectively. RESULTS: Both groups of asthmatics (AERD, n = 240; ATA, n = 226) had significantly higher uBrTyr, uLTE4 levels, and blood eosinophils than healthy controls (HC) (n = 71) (p < 0.05). ULTE4 levels and blood eosinophils were significantly higher in AERD as compared to ATA (p = 0.004, p < 0.0001, respectively). whereas uBrTyr levels were not significantly different between both asthma phenotypes (p = 0.34). Asthmatics with high levels of uBrTyr (> 0.101 ng/mg Cr), uLTE4 levels (> 800 pg/mg Cr) and blood eosinophils (> 300 cells/ul) were 7 times more likely to have AERD.. However, uBrTyr did not increase the benefit for predicting AERD when uLTE4 and blood eosinophils were already taken into account (p = 0.57). CONCLUSION: UBrTyr levels are elevated both in AERD and ATA as compared to HC, but they could not differentiate between these asthma phenotypes suggesting a similar eosinophilic activation. The addition of uBrTyr to elevated uLTE4 levels and blood eosinophils did not statistically enhance the prediction of AERD diagnosis.

AFM-based nanomechanical characterization of bronchoscopic samples in asthma patients.

Asthma is not a single disease, but recently, it is considered as a syndrome characterized through various clinical presentations and different etiopathologies. Large degree of the disease heterogeneity manifests in distinct characteristics that translate into variability of properties at single cell and molecular levels. Here, we conducted measurements of mechanical properties of bronchial tissue samples collected from patients suffering from asthma. The results obtained from different applied protocols for sample preparation may indicate that deep freezing and storage in liquid nitrogen, followed by consecutive unfreezing of tissue samples, preserve tissue mechanical properties as indicated by a parameter referred here as a tissue relative stiffness index. Tissue relative stiffness index quantifies both the degree of heterogeneity and deformability of tissue samples regarding healthy one. These studies demonstrate that the freezing protocol, optimized towards asthma tissue, can facilitate atomic force microscopy use what, together with recent findings on standardization of elasticity measurements, enables the measurements of large group of samples with minimized influence of errors stemming from the applied methodology of tissue stiffness determination.

Diagnostic Accuracy of Urinary LTE4 Measurement to Predict Aspirin-Exacerbated Respiratory Disease in Patients with Asthma.

BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) are distinguished from patients with aspirin-tolerant asthma (ATA) by significantly higher baseline concentrations of urinary leukotriene E4 (uLTE4). However, an overlap between the individual values of the groups exists. OBJECTIVE: The objective of this study was to estimate the discriminative value of uLTE4 concentration in differentiating between patients with AERD and patients with ATA and evaluate the diagnostic accuracy of uLTE4 measurement alone and added to clinical parameters to predict AERD diagnosis in patients with asthma. METHODS: Clinical data were collected from questionnaires. Spirometry, skin prick tests, total IgE, and blood eosinophilia were evaluated. ULTE4 concentrations were measured in morning urine samples by enzyme-linked immune assay (ELISA). RESULTS: Patients with AERD (n = 247) had significantly higher uLTE4 concentrations than those with ATA (n = 239). The uLTE4 concentration of 800.0 pg/mg creatinine as measured by ELISA on a spot sample best discriminated the 2 groups (area under the curve 0.7; 95% confidence interval 0.66-0.74, sensitivity 49%, specificity 81%). The positive predictive value and negative predictive value (NPV), after considering the prevalence of AERD in the population of asthmatics, were 16% and 96%, respectively. Nasal polyps, upper airway symptoms, nasal corticosteroid treatment, asthma exacerbations, forced expiratory volume in the 1 second predicted, and age of asthma onset were independent predictors of AERD diagnosis. The addition of elevated uLTE4 concentration to the set of clinical parameters enhanced slightly the prediction of AERD diagnosis beyond the level predicted by clinical parameters (P = .036). CONCLUSIONS: A set of typical clinical parameters has a superior accuracy in prediction of AERD diagnosis than the measurement of uLTE4 concentration alone. The addition of uLTE4 concentration to clinical parameters slightly enhances the prediction of AERD diagnosis, especially due to a high NPV.