Unlocking Diagnostic Precision: FATE Protocol Integration with BLUE and eFAST Protocols for Enhanced Pre-Hospital Differential Diagnosis of Pleural Effusion Manifested as Dyspnea in Adults-A Pilot Study.

Background: Dyspnea commonly stems from combined myocardial and pulmonary dysfunction, posing challenges for accurate pre-hospital diagnosis. Limited diagnostic capabilities hinder the differentiation of cardiac and pulmonary issues. This study assesses the efficacy of combined cardiac and pulmonary ultrasound using the BLUE, eFAST, and FATE protocols. Methods: Participants were consecutively enrolled from dyspnea-related emergency calls in Warsaw, Poland, from 4 April 2022, to 15 June 2023. Patients with pleural effusion were identified through pre-hospital and in-hospital radiological assessments. Pre-hospital thoracic ultrasonography followed the BLUE, eFAST, and FATE protocols, alongside comprehensive clinical assessments. The pre-hospital diagnoses were juxtaposed with the with hospital discharge diagnoses. Results: Sixteen patients (8 men, 8 women; median age: 76 years) were enrolled. Inter-rater agreement for the BLUE protocol was substantial (κ = 0.78), as was agreement for eFAST (κ = 0.75), with almost perfect agreement for combined protocol assessment (κ = 0.83). Left ventricle hypokinesis, identified via the FATE protocol, significantly correlated with hospital-diagnosed decompensated heart failure as the primary cause of dyspnea. Sensitivity and specificity were 1.0 (95%CI: 0.62-1.0) and 0.6 (95%CI: 0.15-0.95), respectively. Positive predictive value was 0.85 (95%CI: 0.55-0.98), and diagnostic accuracy was 0.86 (95%CI: 0.62-0.98). Conclusions: Integrating the FATE protocol into BLUE and eFAST enhances pre-hospital differential diagnosis accuracy of pleural effusion in adults. This synergistic approach streamlines diagnostic processes and facilitates informed clinical decision-making. Larger-scale validation studies are needed for broader applicability.

Ultrasound on the Frontlines: Empowering Paramedics with Lung Ultrasound for Dyspnea Diagnosis in Adults-A Pilot Study.

Lung transthoracic ultrasound (LUS) is an accessible and widely applicable method of rapidly imaging certain pathologies in the thorax. LUS proves to be an optimal tool in respiratory emergency medicine, applicable in various clinical settings. However, despite the rapid development of bedside ultrasonography, or point-of-care (POCUS) ultrasound, there remains a scarcity of knowledge about the use of LUS in pre-hospital settings. Therefore, our aim was to assess the usefulness of LUS as an additional tool in diagnosing dyspnea when performed by experienced paramedics in real-life, pre-hospital settings. Participants were recruited consecutively among patients who called for an emergency due to dyspnea in the Warsaw region of Poland. All the enrolled patients were admitted to the Emergency Department (ED). In the prehospital setting, a paramedic experienced in LUS conducted an ultrasonographic examination of the thorax, including Bedside Lung Ultrasound in Emergency (BLUE) and extended Focused Assessment with Sonography for Trauma (eFAST) protocols. The paramedic's diagnosis was compared to the ED diagnosis, and if available, to the final diagnosis established on the day of discharge from the hospital. We enrolled 44 patients in the study, comprising 22 (50%) men and (50%) women with a median age of 76 (IQR: 69.75-84.5) years. The LUS performed by paramedic was concordant with the discharge diagnosis in 90.91% of cases, where the final diagnosis was established on the day of discharge from the hospital. In cases where the patient was treated only in the ED, the pre-hospital LUS was concordant with the ED diagnosis in 88.64% of cases. The mean time of the LUS examination was 63.66 s (SD: 19.22). The inter-rater agreement between the pre-hospital diagnosis and ER diagnosis based on pre-hospital LUS and complete ER evaluation was estimated at k = 0.822 (SE: 0.07; 95%CI: 0.68, 0.96), indicating strong agreement, and between the pre-hospital diagnosis based on LUS and final discharge diagnosis, it was estimated at k = 0.934 (SE: 0.03; 95%CI: 0.88, 0.99), indicating almost perfect agreement. In conclusion, paramedic-acquired LUS seems to be a useful tool in the pre-hospital differential diagnosis of dyspnea in adults.

Study protocol for connective tissue disease-associated interstitial lung disease trial (TEL-CTD-ILD): A randomized controlled trial of a home-based telemonitoring of treatment effects.

INTRODUCTION: Interstitial lung disease is one of the most severe pulmonary complications related to connective tissue diseases, resulting in substantial morbidity and mortality. Telepneumology has the potential to improve the long-term management of patients with CTD-ILD. We propose a randomized controlled trial to evaluate the efficacy of home-based telemonitoring of patients with CTD-ILD, in whom treatment was initiated. MATERIALS AND METHODS: We will conduct a randomized controlled trial comparing the standard of care with a telemonitoring program. Telemonitoring will start 10 to 14 days before treatment and will be carried out for three months of therapy. After initial training, patients from the intervention group will perform daily spirometry (FVC), transdermal pulse oximetry, pulse and blood pressure measurements, activity measurement (accelerometry), and assessment of the severity of cough and dyspnea. The results will be reported using a telemetric system designed by Mediguard® for this study. The primary outcome measure will be the health-related quality of life change using EQ-5D-5L questionnaire and St. George's Respiratory Questionnaire, as measured at stationary visits in both study groups. Secondary outcomes will include assessment of lung function, costs of health service utilization, satisfaction from being telemonitored, dyspnea by mMRC, fatigue by FAS, patients' adherence to recommended medications using the ASCD, anxiety and depression symptoms as measured by HADS, PHQ-9, and side effects of treatment. DISCUSSION: This is the first clinical trial protocol to evaluate home-based telemonitoring to optimize connective tissue disease-associated interstitial lung management. The study aims to provide data on the impact of telemonitoring on quality of life, evaluation of health status of patients with CTD-ILD using telemonitoring versus standard care. Additionally, we will evaluate the cost-effectiveness of telemonitoring solutions in patients with CTD-ILD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04428957; Registered June 11, 2020; https://clinicaltrials.gov/ct2/show/NCT04428957.

Progressive fibrosis in interstitial lung diseases - proposed definition and management.

Interstitial lung diseases may have an unpredictably progressive course, which is manifested as progression of pulmonary fibrosis, causing an increasing impairment of lung function affecting a poor prognosis. The possibility of an effective antifibrotic treatment is a chance for patients to slow down the progression of the disease, perhaps even extend their life. For this reason, standardization of the definition as well as identification criteria for progressive fibrosis interstitial lung disease is a method for optimizing the management in this group of patients.

Review: Serum Biomarkers of Lung Fibrosis in Interstitial Pneumonia with Autoimmune Features-What Do We Already Know?

Interstitial pneumonia with autoimmune features (IPAF) belongs to a group of diseases called interstitial lung diseases (ILDs), which are disorders of a varied prognosis and course. Finding sufficiently specific and sensitive biomarkers would enable the progression to be predicted, the natural history to be monitored and patients to be stratified according to their treatment. To assess the significance of pulmonary fibrosis biomarkers studied thus far, we searched the PubMed, Medline and Cochrane Library databases for papers published between January 2015 and June 2021. We focused on circulating biomarkers. A primary review of the databases identified 38 articles of potential interest. Overall, seven articles fulfilled the inclusion criteria. This review aims to assess the diagnostic and prognostic value of molecules such as KL-6, SP-A, SP-D, circulating fibrocytes, CCL2, CXCL13, CXCL9, CXCL10 and CXCL11. All of these biomarkers have previously been studied in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPAF is a disorder of a heterogeneous nature. It explains the lack of coherent observations in terms of correlations with functional parameters. There is still no meta-analysis of pulmonary fibrosis biomarkers in IPAF. This is mainly due to the heterogeneity of the methodology and groups analysed in the research. More research in this area is needed.

Diagnosis of sarcoidosis - the updated ATS 2020 recommendations through the prism of everyday clinical practice.

Diagnosis of sarcoidosis is not standardized, but there is a general consensus that it should be based on the following criteria: consistent, adequate clinical presentation, demonstration of the presence of granulomatous lesions in pathomorphological examination (in one or more tissue samples) and the exclusion of alternative causes of granulomatous disease. In this article, the reader will find, briefly presented, the most important position of ATS experts regarding selected aspects of the diagnosis of sarcoidosis, with a comment from the authors of this editorial.

Guidelines of the Polish Respiratory Society for diagnosis and treatment of idiopathic pulmonary fibrosis.

INTRODUCTION: This document presents the guidelines of the Polish Respiratory Society (PTChP, Polskie Towarzystwo Chorób Pluc) for diagnosis and treatment of idiopathic pulmonary fibrosis (IPF), developed by agroup of Polish experts. MATERIAL AND METHODS: The recommendations were developed in the form of answers to previously formulated questions concer-ning everyday diagnostic and therapeutic challenges. They were developed based on acurrent literature review using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: We formulated 28 recommendations for diagnosis (8), pharmacological treatment (12) as well as non-pharma-cological and palliative therapy (8). The experts suggest that surgical lung biopsy (SLB) not be performed in patients with the probable usual interstitial pneumonia (UIP) pattern, with an appropriate clinical context and unanimous opinion of a multidisciplinary team. The experts recommend using antifibrotic agents in IPF patients and suggest their use irrespective of the degree of functional impairment. As regards non-pharmacological and palliative treatment, strong re-commendations were formulated regarding pulmonary rehabilitation, oxygen therapy (in patients with chronic respiratory failure), preventive vaccinations as well as referring IPF patients to transplant centres. Table 1 presents an aggregate list of recommendations. CONCLUSIONS: The Polish Respiratory Society Working Group developed guidelines for IPF diagnosis and treatment.

Sarcoidosis and calcium homeostasis disturbances-Do we know where we stand?

The majority of cases involving hypercalcemia in the setting of sarcoidosis are explained by the overproduction of calcitriol by activated macrophages. Vitamin D takes part in the regulation of granuloma formation. However, using vitamin D metabolites to assess the activity of the disease is still problematic, and its usefulness is disputable. In some cases, though, a calcium metabolism disorder could be a valuable tool (i.e. as a marker of extrathoracic sarcoidosis). Although sarcoidosis does not cause a decrease in bone mineral density, increased incidence of vertebral deformities is noted. Despite increasing knowledge about calcium homeostasis disorders in patients with sarcoidosis, there is still a need for clear guidelines regarding calcium and vitamin D supplementation in these patients.

Epithelial alarmin levels in exhaled breath condensate in patients with idiopathic pulmonary fibrosis: A pilot study.

INTRODUCTION: Interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP) are epithelial alarmins involved in innate immune responses and have been shown to play an important role in chronic lung diseases. No data are available regarding their levels in exhaled breath condensate (EBC) in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To examine IL-25, IL-33 and TSLP levels in the EBC obtained from patients with IPF and compare them to those in healthy controls, patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: Twenty-three patients with asthma, 25 patients with COPD, 15 patients with IPF and 16 healthy controls were studied. Concentrations of alarmins in the EBC were evaluated by means of ELISA. RESULTS: IL-25 EBC levels were numerically lowest in IPF (25.33 ± 8.84 pg/ml). However, they did not differ significantly from healthy subjects (43.18 ± 5.53 pg/ml), but were significantly lower compared to asthma (72.07 ± 6.03 pg/ml; P < .001). IL-33 EBC levels were significantly increased in IPF (3.41 ± 0.55 pg/ml) compared to healthy controls (1.20 ± 0.60 pg/ml; P < .01) but did not differ from asthma (3.68 pg/ml) and COPD levels (2.47 ± 0.34 pg/ml). There were significant correlations between IL-33 EBC levels and lung diffusion capacity of carbon monoxide (DLco ) absolute (r = .63; P < .05) and % of predicted values (r = .67; P < .01) as well as with time since diagnosis (r = -.59; P < .05) in IPF subjects. TSLP was undetectable in examined samples. CONCLUSION: IL-25 and IL-33 are detectable in the EBC obtained from IPF subjects. Increased levels of IL-33 compared to healthy controls indicate its possible role in the pathobiology of IPF.

Overexpression of chitotriosidase and YKL-40 in peripheral blood and sputum of healthy smokers and patients with chronic obstructive pulmonary disease.

Background: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown. Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD. Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated. Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P<0.05 and P<0.01, respectively). A similar pattern was observed for PBMC chitotriosidase mRNA expression (P<0.001). YKL-40 serum concentrations were elevated in healthy smokers and COPD subjects compared to healthy never-smokers (P<0.001 and P<0.01, respectively). In sputum, YKL-40 levels were increased in COPD compared to healthy never-smokers (P<0.01). PBMC YKL-40 mRNA expression was increased in COPD and healthy smokers compared to healthy never-smokers (P<0.0001). No associations were found between chitotriosidase or YKL-40 peripheral blood levels and sputum levels. Conclusions: Our results demonstrate that chitotriosidase and YKL-40 are overexpressed in peripheral blood and airways in both healthy smokers and COPD subjects which may indicate smoking-related activation of macrophages, neutrophils, and epithelial cells.

Diagnostic and treatment standards in idiopathic pulmonary fibrosis in the era of antifibrotic drugs in Poland: A real-world practice survey.

Background Currently, only two drugs have been shown to modify the inevitable natural history of idiopathic pulmonary fibrosis (IPF). Changes in the reimbursement policy for antifibrotic drugs in Poland have led to the availability of pirfenidone from January 2017 and nintedanib from March 2018 for the treatment of Polish patients with IPF. This study aimed to evaluate the possible changes and shortcomings in the clinical practice standards in IPF in the era of access to antifibrotic therapy in Poland. Methods A real-world data survey was performed among physicians attending the Polish Respiratory Society Congress held in May 2018. The present survey was a follow-up to the previous survey undertaken in 2016, before the availability of antifibrotics in Poland. Results A total of 99 physicians participated in the survey, among which 80% were pulmonologists. The majority of participants (83%) represented hospital-based clinicians and most of them (93%) were involved in interstitial lung diseases (ILD) management. As many as 63% of the respondents elaborate the final diagnosis of IPF working with the expert radiologist routinely, 47% do that in the cooperation with other pulmonologists, and if a biopsy was performed 39% discuss its results with the expert pathologist. Bronchoalveolar lavage (BAL) and surgical lung biopsy (SLB) would never be recommended in the differential diagnosis of IPF by 9% and 16% of the respondents, respectively. Corticosteroids (CS) or a combination of CS and immunosuppressants (IS) is still recommended by 22% of participants. Proton pump inhibitors (PPI) in the case of symptomatic GERD are prescribed by 44% of the respondents, and 12% prescribe PPI regardless of GERD symptoms. Pirfenidone is used by 70%, and nintedanib by 48% of the respondents. Only 39% of the respondents refer patients with IPF to professional rehabilitation centers. Conclusions The level of cooperation between pulmonologists and other specialists in the diagnostic workup of IPF is unsatisfactory. IPF treatment practices in the era of access to effective drugs in Poland require immediate improvement. There is an urgent need to develop the local Polish practical guidelines to improve the management of IPF.

QuantiFERON-TB-GOLD In-Tube in patients with sarcoidosis.

INTRODUCTION: Sarcoidosis and tuberculosis (TB) are the diseases that share many similarities. Mycobacterium tuberculosis (MTB) culture results are the gold standard for the diagnosis of TB, but false positive results are not rare. The aim was to evaluate the utility of QFT in detecting latent TB infection in a group of sarcoidosis patients with negative history of TB and negative culture/BACTEC results, and checking sarcoidosis activity influence on the QFT results. Additionally, we assessed if QFT negative result may strengthen the suspicion that positive culture/BACTEC results are false positive. MATERIAL AND METHODS: 37 culture-negative and 6 culture-positive sarcoidosis patients were enrolled. On the basis of clinical and radiological data TB was considered unlikely (false-positive results). A control group consisted of age-matched subjects with excluded TB (n = 37). QuantiFERON-TB GOLD In-Tube (QIAGEN, USA) was used according to the manual. Test validity was checked basing on the results obtained from a low-risk (n = 21) and active TB group (n = 23). RESULTS: The frequency of positive results tended to be higher in MTB(-) sarcoidosis (24.3% vs. 13.5% for the control group, p = 0.37), but was similar to the general population. None of culture-positive sarcoidosis patients was QFT-positive. The positive results were equally distributed among patients with active and inactive sarcoidosis. CONCLUSIONS: QFT has been found to be the useful test for the detection of latent TB infection in sarcoidosis patients. In addition, we confirm that sarcoidosis activity does not negatively influence the result of QFT. Moreover, QFT would be proposed as a cost-saving diagnostic test providing additional diagnostic information when false positive MTB culture result in the sarcoidosis patient is highly suspected. However, in each case clinical, radiological and epidemiological data should be considered before taking the therapeutic decision.

Skin condition and its relationship to systemic inflammation in chronic obstructive pulmonary disease.

BACKGROUND: The systemic (extrapulmonary) effects and comorbidities of chronic obstructive pulmonary disease (COPD) contribute substantially to its burden. The supposed link between COPD and its systemic effects on distal organs could be due to the low-grade systemic inflammation. The aim of this study was to investigate whether the systemic inflammation may influence the skin condition in COPD patients. MATERIALS AND METHODS: Forty patients with confirmed diagnosis of COPD and a control group consisting of 30 healthy smokers and 20 healthy never-smokers were studied. Transepidermal water loss, stratum corneum hydration, skin sebum content, melanin index, erythema index, and skin temperature were measured with worldwide-acknowledged biophysical measuring methods at the volar forearm of all participants using a multifunctional skin physiology monitor. Biomarkers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), were measured in serum using commercially available enzyme-linked immunosorbent assays. RESULTS: There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level (P<0.05), but not for transepidermal water loss and erythema index. No significant difference was noted between COPD patients and smokers in any of the biophysical properties of the skin measured. The mean levels of hsCRP and IL-6 in serum were significantly higher in COPD patients and healthy smokers in comparison with healthy never-smokers. There were significant correlations between skin temperature and serum hsCRP (R=0.40; P=0.02) as well as skin temperature and serum IL-6 (R=0.49; P=0.005) in smokers. Stratum corneum hydration correlated significantly with serum TNF-α (R=0.37; P=0.01) in COPD patients. CONCLUSION: Differences noted in several skin biophysical properties and biomarkers of systemic inflammation between COPD patients, smokers, and healthy never-smokers may suggest a possible link between smoking-driven, low-grade systemic inflammation, and the overall skin condition.

Idiopathic pulmonary fibrosis (IPF) - common practice in Poland before the "antifibrotic drugs era".

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and debilitating lung disease with a median survival time of 3-5 years. For now, pirfenidone (PIR) and nintedanib (NTB) are the only drugs that can slow down the disease's progression. In Poland, these drugs, although registered for legal use, had not been reimbursed for IPF patients until the end of the year 2016. Aim of the study was to assess what was common practice in terms of diagnosis and treatment in the period before antifibrotic drugs became available for IPF patients in Poland. MATERIAL AND METHODS: We performed a survey among participants of two nationwide pulmonological congresses held in 2016. RESULTS: One hundred and fifty physicians took part in the study. Only 55% of respondents would reach their final diagnosis in collaboration with a radiologist. Just 40% of those sending patients for surgical lung biopsy (SLB) would discuss the case directly with a pathologist. 22% would never refer the patient suspected of having IPF for SLB. 85% believed that bronchoalveolar lavage (BAL) may be useful for diagnosis. 41% of respiratory professionals would not use any drug for the treatment of IPF patients. 23% of physicians would prescribe corticosteroids in high doses (CS), either in monotherapy or in combination with other drugs. Only 43% of respondents would use antacid drugs in case of symptomatic gastro-oesophageal reflux disease (GERD), and only 11% would prescribe these drugs regardless of GERD diagnosis. CONCLUSIONS: The majority of Polish pulmonologists were not supported by radiologists and pathologists in the diagnostic process. Treatment standards were unsatisfactory, mostly due to a lacking of reimbursement regulations. Further education is necessary to improve management of IPF patients in Poland.

The Role of Mitochondria and Oxidative/Antioxidative Imbalance in Pathobiology of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. The major risk factor of COPD, which has been proven in many studies, is the exposure to cigarette smoke. However, it is 15-20% of all smokers who develop COPD. This is why we should recognize the pathobiology of COPD as involving a complex interaction between several factors, including genetic vulnerability. Oxidant-antioxidant imbalance is recognized as one of the significant factors in COPD pathogenesis. Numerous exogenous and endogenous sources of ROS are present in pathobiology of COPD. One of endogenous sources of ROS is mitochondria. Although leakage of electrons from electron transport chain and forming of ROS are the effect of physiological functioning of mitochondria, there are various intra- and extracellular factors which may increase this amount and significantly contribute to oxidative-antioxidative imbalance. With the coexistence with impaired antioxidant defence, all these issues lead to oxidative and carbonyl stress. Both of these states play a significant role in pathobiology of COPD and may account for development of major comorbidities of this disease.