Interleukin 16 and 25 (IL-17E) and Clinical Outcomes in Exacerbation of COPD-A Pilot Study.

Background: Exacerbation of chronic obstructive pulmonary disease (ECOPD) significantly impact health status, hospitalization rates, and disease progression, and are linked to increased mortality. Predictive factors for ECOPD are therefore of considerable interest. The limited understanding of interleukin 16 (IL-16) and IL-25 role in ECOPD provided the rationale for this study. Methods: Fifty ex-smokers diagnosed with COPD (22 ECOPD and 28 patients in the stable phase of the disease) underwent prospective analysis to evaluate the role of I IL-25 as predictive markers of clinical outcomes in ECOPD. Results: We observed a significantly lower IL-16 and higher IL-25 concentrations among ECOPD patients (p = 0.002 and p = 0.01 respectively). We also detected a significant negative correlation between IL-16 and neutrophil-to-lymphocyte ratio (NLR) (p = 0.04) and a significant negative correlation between IL-25 concentration and absolute eosinophil count (p = 0.04). In the entire group, we observed a positive correlation between IL-16 and both FEV1 and FVC, both expressed as a percentage of reference value, (p = 0.002 and p = 0.0004 respectively). However, after stratification to ECOPD and stable COPD group, significance maintained for FVC (p = 0.045 for ECOPD and p = 0.02 for stable COPD). In survival analysis, we detected significantly lower all-cause mortality for 3rd tertile of IL-16 concentrations, with a hazard ratio of 0.33 (95%CI: 0.11-0.98; p = 0.04). Conclusions: Lower IL-16 levels among ECOPD patients may indicate a feedback mechanism linked to heightened Th1 response activation. Observed correlations with ventilatory parameters and survival also seems to reflect this mechanism. The higher IL-25 concentrations observed in ECOPD patients, along with the negative correlation with absolute eosinophil count and eosinopenia, suggest multifactorial regulation and independent functions of eosinophils and IL-25. Hypothetically, this paradox may be related to the Th1/Th2 imbalance favoring Th1 response. Obtained results should be reproduced in larger size samples.

Lung fibrosis in sarcoidosis. Is there a place for antifibrotics?

Sarcoidosis, an enigmatic disease with unknown etiology, is characterized by inflammation and the potential involvement of various organs, predominantly the lungs and intrathoracic lymph nodes. Non-caseating granulomas can resolve spontaneously in approximately 60% of cases within 2-3 years. However, sarcoidosis-related mortality has increased. Lung fibrosis, affecting up to 20% of sarcoidosis patients, stands out as a primary cause of mortality. Traditionally, fibrosis is viewed because of prolonged inflammation, necessitating anti-inflammatory treatment with systemic steroids, immunosuppressants, and anti-TNF agents to manage the disease. The recent introduction of antifibrotic drugs such as nintedanib and pirfenidone offers new avenues for treating fibrotic sarcoidosis. Nintedanib, effective in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD), has shown promise in patients with various progressive fibrosing interstitial lung diseases (PF-ILD), including those with sarcoidosis. Pirfenidone, also effective in IPF, has demonstrated potential in managing fibrotic sarcoidosis, though results have been inconclusive due to limited participant numbers in studies. This review explores the theoretical and empirical evidence supporting the use of antifibrotics in sarcoidosis, weighing the benefits and drawbacks. While antifibrotics offer a potential therapeutic approach, further randomized controlled trials are essential to determine their efficacy in fibrotic sarcoidosis. Addressing fibrosis as a continuum of chronic inflammation, the role of antifibrotics in managing sarcoidosis remains an area requiring more in-depth research to improve patient outcomes and advance treatment paradigms.

Determination of the best point of entry of percutaneous insertion of sacroiliac screws depending on patient positioning for surgery: A cadaveric study.

BACKGROUND: The standard starting point for percutaneous sacroiliac screw insertion was initially determined at the intersection of the line posterior to the anterior superior iliac spine and the line continuing the anatomical axis of the femur. The technique was pioneered in patients lying prone in surgery, although it has been used with patients in the supine position. The optimal starting point for patients in both prone and supine positions remains uncertain. OBJECTIVES: This cadaveric study aimed to determine the best entry point for the percutaneous insertion of sacroiliac screws depending on the patient's positioning for surgery. MATERIAL AND METHODS: Kirschner wires (K-wires) were percutaneously inserted into the sacral body of 8th human cadavers. In addition to the so-called standard sacroiliac screw entry point (point A), points located consecutively 1 cm (point B) and 2 cm (point C) cranially from the point along the line, prolonging the femoral axis were also studied. The K-wires were inserted into the studied entry points on the right side in a supine position and on the left side of the same cadaver in a prone position. The placement of the K-wires was assessed using radiographic imaging and cadaver dissection. RESULTS: An analysis of the K-wire placement in the supine position revealed incorrect positioning of 100% of the K-wires inserted at entry point A and 87% at entry point B. All the K-wires inserted in the supine position at entry point C were correctly placed. All K-wires inserted in the prone position were correctly positioned. CONCLUSIONS: All 3 studied entry points enabled the correct placement of orthopedic implants for prone position surgery. The best entry point for surgery performed in the supine position was located 2 cm cranially from the standard entry point, along the line prolonging the femoral axis.

The Short-Term Efficacy of a Three-Week Pulmonary Rehabilitation Program among Patients with Obstructive Lung Diseases.

Introduction: The recommended duration for pulmonary rehabilitation stands at a minimum of six weeks; however, this stipulation may pose constraints in various countries due to financial limitations imposed by insurance companies and/or national health funds, as is the case in Poland. Consequently, our study endeavors to analyze the short-term outcomes stemming from a condensed three-week PR regimen administered to patients diagnosed with chronic obstructive pulmonary disease (COPD), asthma, and the concomitance of these conditions (COPD-A)-this is an approach that is standard in the rehabilitation protocols endorsed by our national health fund. Methods: Patients diagnosed with COPD, asthma, and COPD-A, referred to the PR program, underwent retrospective analysis to evaluate the short-term efficacy of a three-week PR program. Patients underwent comprehensive assessment by respiratory physicians and rehabilitation consultants, leading to individualized PR programs. Clinical evaluations occurred at program onset and completion. Results: 125 patients participated: 37 COPD, 61 asthma, and 27 COPD-A. Significant improvements were observed in the COPD Assessment Test (CAT), the consensus-based GINA symptom control tool (GINA-SCT), the Modified Medical Research Council (mMRC) scale, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and the 6-min walk test (6 MWT) distance, as well as in the St. George's Respiratory Questionnaire (SGRQ) scores. All groups experienced reduced dyspnea severity and improved exercise tolerance. FEV1 and FVC improved in asthma and COPD-A, but not significantly in COPD. Multivariable logistic regression identified predictive factors for PR response. Conclusions: The study supports the short-term efficacy of the three-week PR program in improving clinical outcomes, exercise tolerance, and quality of life in COPD and asthma patients. Tailoring interventions based on predictors of PR response can optimize outcomes. Further research, particularly of the COPD-A group, is needed for individualized approaches. Larger sample sizes are necessary to confirm our findings.

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.

Frontiers of Deep-Red Emission of Mn4+ Ions with Ruddlesden-Popper Perovskites.

It is well-known that the chemical composition of the host material significantly affects the spectroscopic performance of transition metal ions. However, it is worth noting that also the structure and symmetry of crystallographic sites play significant roles in transition metal ion luminescence. In this study, we demonstrate three perovskite structures of strontium titanate forming so-called Ruddlesden-Popper phases doped with Mn4+ ions. The observed reduction in the average Ti4+-O2- distance in the series SrTiO3-Sr2TiO4-Sr3Ti2O7 allowed for a record-breaking shift in the spectral position of Mn4+ emission band with a maximum of around 734 nm and led to an improvement of the already impressive thermometric performance of SrTiO3:Mn4+ in ratiometric and lifetime-based approaches. This research encourages a further search for structures that, with the help of the developed correlations between structural and optical properties, could lead to the discovery of phosphors beyond the limits established so far.

Characteristics of Interstitial Pneumonia With Autoimmune Features (IPAF): Protocol for a Multicenter Prospective Study.

BACKGROUND: "Interstitial lung disease" (ILD) is a broad term encompassing diseases of different backgrounds. "Interstitial pneumonia with autoimmune features" (IPAF) is a recent term that implies the presence of autoimmunity. OBJECTIVE: This study aims to determine the characteristics of Polish patients with IPAF, compare them with patients with other interstitial pneumonias, and search for the prognostic and diagnostic biomarkers of IPAF in serum and bronchoalveolar lavage fluid (BALF). METHODS: This multicenter prospective study plans to recruit 240 participants divided into 1 study group and 2 control groups. Biological fluid samples will be collected according to Polish Respiratory Society management guidelines and stored at -80°C for further tests. Prospective 5-year observations of 60 newly diagnosed individuals are planned. The study will be divided into subsections. First, we plan to characterize Polish patients with IPAF (study group) against their peers with other ILDs (2 control groups). Control group 1 will comprise patients with idiopathic ILDs, including mainly idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Control group 2 will comprise patients with connective tissue disease-associated interstitial lung diseases, such as rheumatoid arthritis, systemic sclerosis, polymyositis, dermatomyositis, Sjögren's syndrome, mixed connective tissue disease, and systemic lupus erythematosus. Radiological and functional parameters will be analyzed. Patients will be compared in terms of high-resolution computed tomography results, the 6-minute walking test performance, and pulmonary function test parameters. The diagnosis of IPAF will be reassessed on a regular basis through multidisciplinary discussion in order to determine its clinical stability. In the laboratory arm, inflammation and fibrosis pathways will be assessed. Cytokine levels (interleukin 8, transforming growth factor beta 1, chemokine C-C motif ligand [CXCL]18, CXCL1, surfactant protein [SP]-A, SP-D, Krebs von den Lungen-6 protein, and chitinase 1) will be measured in serum and BALF. A comparative analysis of serum and BALF cytokine levels will be performed in order to establish potential differences between systemic and local inflammatory pathways. In the quality of life (QoL) arm of the study, dyspnea and cough and their impact on various aspects of the QoL will be assessed. Depression and anxiety will be measured with the Hospital Anxiety and Depression Modified Scale and the 9-item Patient Health Questionnaire, and potential correlations with symptom prevalence will be assessed. RESULTS: This study will start recruiting patients to phase 1 in October 2023. The final results will be available in 2028. We plan to publish preliminary results after 2-3 years from the start of phase 1. CONCLUSIONS: This study will be a step toward a better understanding of IPAF etiopathogenesis and outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44802.

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.

Is Pulmonary Involvement a Distinct Phenotype of Post-COVID-19?

(1) Background: COVID-19 infection often provokes symptoms lasting many months: most commonly fatigue, dyspnea, myalgia and mental distress symptoms. In this study, we searched for clinical features of post-COVID-19 condition (PCC) and differences between patients with and without pulmonary involvement. (2) Methods: A total of 282 patients with a mean age of 57 years (SD +/- 12 years) underwent assessment up to 12 weeks after COVID-19 recovery. The course of acute disease, past medical history and clinical symptoms were gathered; pulmonary function tests were performed; radiographic studies were assessed and follow-up examinations were conducted. Patients with and without detectable pulmonary lesions were divided into separate groups. (3) Results: Patients within the pulmonary group were more often older (59 vs. 51 y.o.; p < 0.001) males (p = 0.002) that underwent COVID-19-related hospitalization (p < 0.001) and were either ex- or active smokers with the median of 20 pack-years. We also managed to find correlations with hypertension (p = 0.01), liver failure (p = 0.03), clinical symptoms such as dyspnea (p < 0.001), myalgia (p = 0.04), headache (p = 0.009), sleeplessness (p = 0.046), pulmonary function tests (such as FVC, TLCO, RV and TLC; p < 0.001) and several basic laboratory tests (D-dimer, cardiac troponin, WBC, creatinine and others). (4) Conclusions: Our results indicate that initial pulmonary involvement alters the PCC, and it can be used to individualize clinical approaches.

Expectations, symptoms, and quality of life before and after 1 year of Pirfenidone treatment in patients with idiopathic pulmonary fibrosis: A single-arm, open-label nonrandomized study.

Background and Aims: Antifibrotic therapies reduce lung function decline in patients with idiopathic pulmonary fibrosis (IPF). This single-arm, open-label, nonrandomized study aimed to determine the influence of antifibrotic treatment on patients' reported symptoms and expectations of the therapy. Methods: Fifty-two patients with confirmed IPF at a mean age of 65 ± 8.63 years (73% male) completed the following surveys at baseline and after 12 months of Pirfenidone treatment: Short Form Healthy Survey (SF-36), St. George's Respiratory Questionnaire (SGRQ), Baseline Dyspnea Index (BDI), Fatigue Assessment Scale (FAS), Leicester Cough Questionnaire (LCQ), and Patient's Needs and Expectations Authors' Survey. Results: The most important patients' needs were access to novel therapy, fast and easy access to health centers specializing in IPF treatment, and the improvement of the general condition or the maintenance of its level. These needs did not change with time, except for the significantly more important right of deciding on disease management after 12 months of treatment (p = 0.014). The quality of life per SF-36, after 1 year of Pirfenidone treatment, significantly improved in the physical cumulative score (p = 0.004) and mental cumulative score (p = 0.003). Significant deteriorations were observed in bodily pain and vitality. For the remaining questionnaires (SGRQ, BDI, FAS, and LCQ), no significant changes in the course of the study were noticed. Around one in 10 patients subjected to Pirfenidone therapy had achieved general symptom improvement in all areas; that is, quality of life improvement as well as cough and dyspnea reduction. Conclusions: One year of antifibrotic treatment resulted in a general improvement in the quality of life per the SF-36 questionnaire. Patients' expectations of disease management did not change; also, access to novel therapies and easy access to health centers specializing in IPF management remained their top needs.

Oxidative Biomarkers Associated with the Pulmonary Manifestation of Post-COVID-19 Complications.

INTRODUCTION: The role of mitochondria in post coronavirus disease 2019 (post-COVID-19) complications is unclear, especially in the long-term pulmonary complications. This study aims to investigate the association between post-COVID-19 pulmonary complications and mitochondrial regulatory proteins in the context of oxidative stress. METHODOLOGY: Patients who had recovered from COVID-19 were enrolled. According to the evidence of persistent interstitial lung lesions on computed tomography (CT), patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(-)). We randomly selected 80 patients for investigation (40 subjects for each group). Biomarkers levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum concentrations of mitochondrial regulatory proteins were significantly higher in the P(+) group, including PTEN-induced kinase 1 (PINK1): 1.62 [1.02-2.29] ng/mL vs. 1.34 [0.94-1.74] ng/mL (p = 0.046); Dynamin-1-like protein (DNM1L): 1.6 [0.9-2.4] ng/mL IQR vs. 0.9 [0.5-1.6] ng/mL (p = 0.004); and Mitofusin-2 (MFN2): 0.3 [0.2-0.5] ng/mL vs. 0.2 [0.1-0.3] ng/mL IQR (p = 0.001). Patients from the P(+) group also had higher serum levels of chemokine ligand 18 (PARC, CCL18), IL-6, and tumour necrosis factor-alpha (TNF-α) cytokines than the P(-) group. The concentration of interferon alpha (IFN-α) was decreased in the P(+) group. Furthermore, we observed statistically significant correlations between the advanced glycation end product (sRAGE) and TNF-α (Pearson's factor R = 0.637; p < 0.001) and between serum levels of DNM1L and IFN-α (Pearson's factor R = 0.501; p = 0.002) in P(+) patients. CONCLUSIONS: Elevated concentrations of mitochondrial biomarkers in post-COVID-19 patients with long-term pulmonary complications indicate their possible role in the pathobiology of COVID-19 pulmonary sequelae. Oxidative stress is associated with the immune response and inflammation after COVID-19. TNF-α could be a promising biomarker for predicting pulmonary complications and may be a potential target for therapeutic intervention in patients with post-COVID-19 complications.

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.

Calcium, Phosphate, and Vitamin D Status in Patients with Sarcoidosis-Associations with Disease Activity and Symptoms.

Sarcoidosis is a systemic granulomatous disease with a variety of presentations. One of the known symptoms are altered vitamin D metabolism and hypercalcemia. In our study, we aimed to assess associations between disease activity, inflammatory parameters, and vitamin D and calcium status. The secondary aim was to find any dependencies between calcium and vitamin D metabolism and fatigue and quality of life in patients with sarcoidosis. We enrolled 58 patients with sarcoidosis (47 classified as active disease, 11 classified as non-active) and compared them with 25 healthy volunteers. Calcium concentration was significantly higher in the study group than in healthy controls. It correlated with some inflammatory markers but not with vitamin D status. Not calcium nor vitamin D, but phosphate concentration correlated with life quality was assessed with the use of the Sarcoidosis Health Questionnaire. An association between phosphate concentration and fatigue was also noted, but it did not reach statistical significance. Calcium concentration was higher in patients with sarcoidosis, but it was not an indicator of the disease activity, while phosphate concentration was significantly lower in patients with active sarcoidosis.

Chronotype and the Big-Five personality traits as predictors of chronic fatigue among patients with sarcoidosis. A cross-sectional study.

BACKGROUND: Sarcoidosis may seriously hamper patients' quality of life despite fairly good prognosis. OBJECTIVES: To assess the relationship between the Big Five personality traits, chronotype and severity of fatigue symptoms, in the context of selected clinical variables and general mental health among patients with sarcoidosis. METHODS: The study group comprised 60 patients with a confirmed diagnosis of sarcoidosis. They were asked to share relevant clinical data and complete a set of questionnaires: Fatigue Asessment Scale (FAS), General Health Questionnaire (GHQ-28), the NEO Five Factor Inventory and Composite Scale of Morningness. RESULTS: In linear regression analysis, FAS score was predicted by female sex, active sarcoidosis status, Morning Affect and Conscientiousness. In principal component analysis, FAS score and all GHQ-28 subscale scores (somatic symptoms, anxiety/insomnia, social dysfunction and depressive symptoms) formed a single component explaining 60% of variance. The factor loading for each variable exceeded 0.6. CONCLUSIONS: The psychological burden appeared to rise with the severity of the fatigue, regardless the inactive/active phase of sarcoidosis. The severity of fatigue may be linked to patient's poor morning affect. The profile of psychological burden presented by the patients may be associated with their personality and clinical presentation of sarcoidosis.

Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial.

INTRODUCTION: Oral pirfenidone reduces lung function decline and mortality in patients with idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects, including nausea, rash, photosensitivity, weight loss and fatigue. Reduced doses may be suboptimal in slowing disease progression. METHODS: This phase 1b, randomised, open-label, dose-response trial at 25 sites in six countries (Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12618001838202) assessed safety, tolerability and efficacy of inhaled pirfenidone (AP01) in IPF. Patients diagnosed within 5 years, with forced vital capacity (FVC) 40%-90% predicted, and intolerant, unwilling or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulised AP01 50 mg once per day or 100 mg two times per day for up to 72 weeks. RESULTS: We present results for week 24, the primary endpoint and week 48 for comparability with published trials of antifibrotics. Week 72 data will be reported as a separate analysis pooled with the ongoing open-label extension study. Ninety-one patients (50 mg once per day: n=46, 100 mg two times per day: n=45) were enrolled from May 2019 to April 2020. The most common treatment-related adverse events (frequency, % of patients) were all mild or moderate and included cough (14, 15.4%), rash (11, 12.1%), nausea (8, 8.8%), throat irritation (5, 5.5%), fatigue (4, 4.4%) and taste disorder, dizziness and dyspnoea (three each, 3.3%). Changes in FVC % predicted over 24 and 48 weeks, respectively, were -2.5 (95% CI -5.3 to 0.4, -88 mL) and -4.9 (-7.5 to -2.3,-188 mL) in the 50 mg once per day and 0.6 (-2.2 to 3.4, 10 mL) and -0.4 (-3.2 to 2.3, -34 mL) in the 100 mg two times per day group. DISCUSSION: Side effects commonly associated with oral pirfenidone in other clinical trials were less frequent with AP01. Mean FVC % predicted remained stable in the 100 mg two times per day group. Further study of AP01 is warranted. TRIAL REGISTRATION NUMBER: ACTRN12618001838202 Australian New Zealand Clinical Trials Registry.

Concise, Practical Review on Transthoracic Lung Ultrasound in Prehospital Diagnosis of Dyspnea in Adults.

Ultrasonography is a relatively young but widely recognized method of imaging parenchymal organs, including the lungs. Our concise, practical review on transthoracic lung ultrasound (LUS) in the prehospital diagnosis of dyspnea in adults attempts to summarize current knowledge in the field. Furthermore, we discussed POCUS protocols in the analyzed context, discussing their usefulness. We concluded that bedside ultrasonography, or point of care (POCUS), is developing rapidly; however, the knowledge about the use of LUS in a pre-hospital setting is scarce, highlighting the need for further research in this field. Additionally, despite the possibility of using various ultrasound protocols in diagnosing a patient with dyspnea, there is no comprehensive and, at the same time, highly sensitive and specific protocol covering a satisfactory saccade of differential diagnosis of this symptom. It seems reasonable to conduct further targeted research to create such a dedicated solution.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

Soluble ITGaM and ITGb2 Integrin Subunits Are Involved in Long-Term Pulmonary Complications after COVID-19 Infection.

(1) Introduction: The role of soluble integrins in post-COVID-19 complications is unclear, especially in long-term pulmonary lesions. The purpose of this study was to investigate the association between soluble ITGa2, ITGaM and ITGb2 integrin subunits and long COVID-19 pulmonary complications. (2) Methodology: Post-COVID-19 patients were enrolled. According to the evidence of persistent interstitial lung lesions on CT, patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(-)). We randomly selected 80 patients for further investigation (40 subjects for each group). Levels of ITGa2, ITGaM and ITGb2 integrin subunits were determined by ELISA assay. (3) Results: The serum concentration of sITGaM and sITGb2 were significantly higher in the P(+) group (sITGaM 18.63 ng/mL [IQR 14.17-28.83] vs. 14.75 ng/mL [IQR 10.91-20] p = 0.01 and sITGb2 10.55 ng/mL [IQR 6.53-15.83] vs. 6.34 ng/mL [IQR 4.98-9.68] p = 0.002). We observed a statistically significant correlation between sITGaM and sITGb2 elevation in the P(+) group (R = 0.42; p = 0.01). Patients from the P(+) group had a lower (1.82 +/-0.84 G/L) lymphocyte level than the P(-)group (2.28 +/-0.79 G/L), p = 0.03. Furthermore, we observed an inverse correlation in the P(-) group between blood lymphocyte count and sITGb2 integrin subunit levels (R = -0.49 p = 0.01). (4) Conclusions: Elevated concentrations of sITGaM and sITGb2 were associated with long-term pulmonary complications in post-COVID-19 patients. Both sITGaM and sITGb2 may be promising biomarkers for predicting pulmonary complications and could be a potential target for therapeutic intervention in post-COVID-19 patients.

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.