Home Monitoring of Asthma Exacerbations in Children and Adults With Use of an AI-Aided Stethoscope.

PURPOSE: The advent of new medical devices allows patients with asthma to self-monitor at home, providing a more complete picture of their disease than occasional in-person clinic visits. This raises a pertinent question: which devices and parameters perform best in exacerbation detection? METHODS: A total of 149 patients with asthma (90 children, 59 adults) participated in a 6-month observational study. Participants (or parents) regularly (daily for the first 2 weeks and weekly for the next 5.5 months, with increased frequency during exacerbations) performed self-examinations using 3 devices: an artificial intelligence (AI)-aided home stethoscope (providing wheezes, rhonchi, and coarse and fine crackles intensity; respiratory and heart rate; and inspiration-to-expiration ratio), a peripheral capillary oxygen saturation (SpO2) meter, and a peak expiratory flow (PEF) meter and filled out a health state survey. The resulting 6,029 examinations were evaluated by physicians for the presence of exacerbations. For each registered parameter, a machine learning model was trained, and the area under the receiver operating characteristic curve (AUC) was calculated to assess its utility in exacerbation detection. RESULTS: The best single-parameter discriminators of exacerbations were wheezes intensity for young children (AUC 84% [95% CI, 82%-85%]), rhonchi intensity for older children (AUC 81% [95% CI, 79%-84%]), and survey answers for adults (AUC 92% [95% CI, 89%-95%]). The greatest efficacy (in terms of AUC) was observed for a combination of several parameters. CONCLUSIONS: The AI-aided home stethoscope provides reliable information on asthma exacerbations. The parameters provided are effective for children, especially those younger than 5 years of age. The introduction of this tool to the health care system might enhance asthma exacerbation detection substantially and make remote monitoring of patients easier.

Neutrophil/Lymphocyte Ratio (NLR) and Lymphocyte/Monocyte Ratio (LMR) - Risk of Death Inflammatory Biomarkers in Patients with COVID-19.

Aim: The aim of our retrospective study was search for new prognostic parameters, which can help quickly and cheaply identify patients with risk for severe course of SARS-CoV-2 infection. Materials and Methods: The following peripheral blood combination biomarkers were calculated: NLR (neutrophil/lymphocytes ratio), LMR (lymphocyte/monocyte ratio), PLR (platelet/lymphocyte ratio), dNLR (neutrophils/(white blood cells - neutrophils)), NLPR (neutrophil/(lymphocyte × platelet ratio)) in 374 patients who were admitted to the Temporary Hospital no 2 of Clinical Hospital in Bialystok (Poland) with COVID-19. The patients were divided into four groups depending on the severity of the course of COVID-19 using MEWS classification. Results: The NLR and dNLR were significantly increased with the severity of COVID-19, according to MEWS score. The AUC for the assessed parameters was higher in predicting death in patients with COVID-19: NLR (0.656, p=0.0018, cut-off=6.22), dNLR (0.615, p=0.02, cut-off=3.52) and LMR (0.609, p=0.03, cut-off=2.06). Multivariate COX regression analysis showed that NLR median above 5.56 (OR: 1.050, P=0.002), LMR median below 2.23 (OR: 1.021, P=0.011), and age >75 years old (OR: 1.072, P=0.000) had a significant association with high risk of death during COVID-19. Conclusion: Our results indicate that NLR, dNLR, and LMR calculated on admission to the hospital can quickly and easy identify patients with risk of a more severe course of COVID-19. Increase NLR and decrease LMR have a significant predictive value in COVID-19 patient's mortality and might be a potential biomarker for predicting death in COVID-19 patients.

The Diagnostic Value of Inflammatory Markers (CRP, IL6, CRP/IL6, CRP/L, LCR) for Assessing the Severity of COVID-19 Symptoms Based on the MEWS and Predicting the Risk of Mortality.

Introduction: Various diagnostic tools are used to assess the severity of COVID-19 symptoms and the risk of mortality, including laboratory tests and scoring indices such as the Modified Early Warning Score (MEWS). The diagnostic value of inflammatory markers for assessing patients with different severity of COVID-19 symptoms according to the MEWS was evaluated in this study. Materials and Methods: The concentrations of CRP (C-reactive protein) (immunoassay) and IL6 (interleukin 6) (electrochemiluminescence assay) were determined, and CRP/IL6, CRP/L, and LCR ratios were calculated in blood serum samples collected from 374 COVID-19 patients. Results: We demonstrated that CRP, IL6, CRP/IL6, CRP/L, LCR inflammatory markers increase significantly with disease progression assessed based on the MEWS in COVID-19 patients and may be used to differentiating patients with severe and non-severe COVID-19 and to assess the mortality. Conclusion: The diagnostic value of inflammatory markers for assessing the risk of mortality and differentiating between patients with mild and severe COVID-19 was confirmed.

Pru du 1, the Bet v 1-homologue from almond, is a major allergen in patients with birch pollen associated almond allergy.

Background: Almond allergy is common and can manifest in two different forms. Primary almond allergy has been reported to be associated with sensitization to almond legumin Pru du 6. In birchendemic regions, there is a link between birch-pollinosis which is likely based on a cross-reactive Bet v 1 homologue, a yet unidentified allergen in almond. Therefore, we sought to identify and characterize a Bet v 1-homologue in almond. Methods: The expression of a Bet v 1 homologue in almond kernels was confirmed by mass spectrometry. The recombinant protein was produced in Escherichia coli and its cross-reactivity and allergenic potency was analyzed by IgE quantitative and competitive ELISA, immunoblotting and basophil histamine release using sera from 17 almond allergic patients. Results: The identified Bet v 1 homologue received the designation Pru du 1.0101. Pru du 1.0101 bound IgE from 82 % of almond allergic patients. Bet v 1 was able to inhibit IgE-binding to rPru du 1 by 100%, while rPru du 1 inhibited IgE binding to rBet v 1 by 48%. Pru du 1.0101 activated basophils, though 100- to 1000-fold higher concentrations were required for maximum activation in comparison to rBet v 1. Conclusion: Considering the strong inhibition capacity and higher allergenic potency of Bet v 1, the results provide compelling evidence for primary sensitization to Bet v 1 in case of birch pollen associated almond allergy. Combining Pru du 6 and Pru du 1 in diagnostic approaches may help to discriminate between primary and birch-pollen associated almond allergy.

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

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

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

Efficacy of ciclesonide in the treatment of patients with asthma exacerbation.

INTRODUCTION: Progressing deterioration of the lung function, dyspnoea, cough, wheezing and chest tightness are the main features of asthma exacerbations. The first step in the prevention of severe asthma exacerbations is to intensify the anti-inflammatory treatment with high doses of inhaled corticosteroids (ICS). AIM: To assess the efficacy of ciclesonide in patients who have been losing control of asthma despite being treated with medium doses of inhaled corticosteroids and long-acting ß2-agonists (LABA) as the second controller. MATERIAL AND METHODS: The study was conducted in a group of 74 asthmatic patients who have been losing control of their asthma. Subjects entering the study received the following anti-inflammatory interventions: high doses of ciclesonide (1280 µg) or 640 µg of ciclesonide added to a current dose of ICS or a doubled dose of current ICS. RESULTS: Treatment options containing ciclesonide have shown statistically and clinically important advantages (improvement of Asthma Control Test score, reduction in rescue medication consumption, reduction in day and night symptoms score, improvement in spirometry parameters, decrease in exhaled nitric oxide, and no necessity of oral corticosteroids treatment) in comparison to patients for whom medium doses of the previously used inhaled corticosteroid were doubled. CONCLUSIONS: Treating with high doses of ciclesonide is characterised by a quick and potent anti-inflammatory effect as well as prompt clinical improvement along with the proper safety profile in patients experiencing asthma exacerbations.

Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease.

BACKGROUND/AIMS: Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters. METHODS: Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays. RESULTS: Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin. CONCLUSIONS: Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.

Fibroblast growth factor 23, iron and inflammation - are they related in early stages of chronic kidney disease?

INTRODUCTION: Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). MATERIAL AND METHODS: The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). RESULTS: In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen (r = -0.23, p < 0.05) and eGFR (r = -0.36, p < 0.05). CONCLUSIONS: FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.

GDF-15, iron, and inflammation in early chronic kidney disease among elderly patients.

PURPOSE: The aim of the study was to assess GDF-15 and iron status in patients in early stages of chronic kidney disease with a particular emphasis on elderly population in association of classic iron status parameters with novel iron homeostasis biomarkers and inflammatory parameters. METHODS: Serum concentrations of GDF-15, iron (Fe), transferrin saturation, soluble transferrin receptor (sTfR), hepcidin, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6), and hemoglobin were measured in 56 patients ≥65 years of age and in 31 <65 years of age. RESULTS: In patients ≥65 years, serum concentrations of GDF-15 and hsCRP were significantly higher in comparison with younger group. There was no statistically significant difference in hemoglobin, iron, hepcidin, and sTfR concentration between the two studied groups. In both groups GDF-15 was significantly correlated with hemoglobin, eGFR, hsCRP, and IL-6. GDF-15 was significantly higher in patients with anemia in comparison with their non-anemic counterparts. In multivariate analysis, hemoglobin was found to be a predictor of log GDF-15 (beta value = 0.36, P = 0.006, R (2) = 37 %). CONCLUSIONS: An intricate interplay between renal function, anemia, and GDF-15 concentrations awaits further studies, as there are few data regarding pathophysiological role of GDF-15 in diabetes, kidney disease, and other comorbidities. Further understanding regarding the signaling pathways of GDF-15 may help to discover next pieces in the exciting puzzle of GDF-15. Finally, as studies dealing with normal level of GDF-15 in the healthy aged are lacking, it is possible that the higher values of GDF-15 values found in the present study represent values of GDF-15 according to age more than CKD levels.

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease.

BACKGROUND/AIMS: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. METHODS: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. RESULTS: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. CONCLUSION: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.

Changes in blood eosinophilia during omalizumab therapy as a predictor of asthma exacerbation.

INTRODUCTION: Omalizumab is a monoclonal anti-immunoglobulin E antibody developed for the treatment of severe allergic asthma. The number of exacerbations used as a parameter of omalizumab therapy efficacy may be insufficient in many cases due to a relatively short time to first evaluation (16 weeks). Therefore, it is advisable to look for parameters of more prognostic value while continuing omalizumab therapy. AIM: To evaluate usefulness of analysis of changes of blood eosinophilia after 16 weeks of omalizumab therapy as a predictor of asthma exacerbations. MATERIAL AND METHODS: The study was conducted on a group of 13 patients with severe persistent allergic asthma treated with omalizumab. Blood eosinophil counts were measured before and after 16 weeks of anti-IgE therapy. On the basis of percentage of eosinophilia decrease (> 50% or < 50% of the initial value), patients were divided into two groups. Analysis of the asthma exacerbation rate during 12 months and time to first exacerbation was performed. RESULTS: In the group with a high decrease in blood eosinophil counts (group 1) we showed a statistically significantly lower asthma exacerbation rate in 12 months compared with the group with a low decrease in blood eosinophil counts (group 2) (p = 0.02). We also observed the tendency to longer time to first asthma exacerbation in group 1 compared to group 2 (p = 0.06). CONCLUSIONS: Our results showed that a decrease in blood eosinophilia during omalizumab therapy can be a predictor of asthma exacerbation. Evaluation of changes in blood eosinophil count should be taken into the consideration while estimating response to anti-IgE therapy in patients with severe allergic asthma.

Omalizumab treatment in brittle asthma.

Asthma is a heterogeneous disease with variable characteristics such as lung function, symptoms and control, body weight, pattern of inflammation, and response to treatment. Brittle asthma is one of clinical phenotypes of asthma with unclear pathogenic mechanisms and appropriate treatment. Analysis of 2 described cases suggests that omalizumab could be useful in the treatment of brittle allergic asthma.