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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. [ABSTRACT FROM AUTHOR]

Introduction: Chronic obstructive lung diseases, such as asthma and COPD, appear to have a more extensive impact on overall functioning than previously believed. The latest data from clinical trials suggests a potential link between cognitive deterioration and chronic obstructive inflammatory lung disease. This raises the question of whether these diseases affect cognitive functions and whether any relevant biomarker may be identified. Methods: This prospective observational study included 78 patients divided equally into asthma, COPD, and control groups (n=26, 27 and 25 respectively). The participants underwent identical examinations at the beginning of the study and after at least 12 months. The test battery comprised 16 questionnaires (11 self-rated, 5 observer-rated, assessing cognition and mental state), spirometry, and blood samples taken for PKA and CREB mRNA evaluation. Results: A 2.3-fold increase in CREB mRNA was observed between examinations (p=0.014) for all participants; no distinctions were observed between the asthma, COPD, and control groups. Pooled, adjusted data revealed a borderline interaction between diagnosis and CREB expression in predicting MMSE (p=0.055) in COPD, CREB expression is also associated with MMSE (b=0.273, p=0.034) like with the other conducted tests (b=0.327, p=0.024) from COPD patients. No correlations were generally found for PKA, although one significant negative correlation was found between the first and second time points in the COPD group (b=-0.4157, p=0.049). Discussion: Chronic obstructive lung diseases, such as asthma and COPD, may have some linkage to impairment of cognitive functions. However, the noted rise in CREB mRNA expression might suggest a potential avenue for assessing possible changes in cognition, especially in COPD; such findings may reveal additional transcription factors linked to cognitive decline. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Primary pulmonary Hodgkin’s lymphoma (PPHL) is a rare subtype of lymphoma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin-Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic workup involving a multidisciplinary team of clinicians, radiologists, and pathologists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This is the first study assessing the clinical management of severe, isolated dysphonia during post-COVID-19 syndrome. One hundred and fifty-eight subjects met the inclusion criteria for the post-COVID-19 condition as specified by the WHO. Six patients were diagnosed with isolated severe dysphonia, constituting 3.8% of the initial group. The pre- and post-examination protocol consisted of subjective voice self-assessment and routine laryngological examination, followed by an instrumental examination by means of Laryngovideostroboscopy (LVS) and High-Speed Videolaryngoscopy (HSV). The treatment included short-term systemic steroids in decreasing doses, moisturizing inhalations with hyaluronic acid, and protective agents against Laryngopharyngeal Reflux. The kinematic imaging of the glottis performed by means of HSV before treatment showed deviations in the regularity and symmetry of vocal fold vibrations, absence of mucosal wave, and incomplete glottal closure. Improvement of the structural and functional state of the larynx was observed post-treatment. Kymographic sections and Glottal Width Waveform (GWW) graphs obtained from post-treatment HSV recordings showed improvement in vocal fold vibrations. The decrease in mean Jitter and Shimmer was observed, with the following mean values of 3.16 pre-treatment and 2.97 post-treatment for Jitter and 7.16 pre-treatment and 2.77 post-treatment for Shimmer. The post-treatment self-evaluation of voice showed considerable improvement in vocal function and voice quality in all the examined patients. Severe dysphonia in patients with post-COVID-19 syndrome requires urgent ENT diagnosis using instrumental assessment with the evaluation of laryngeal phonatory function and intensive comprehensive treatment. [ABSTRACT FROM AUTHOR]

Background: Although chitin is absent in humans, chitinases are present in healthy subjects and show dysregulated expression in a variety of diseases resulting from abnormal tissue injury and repair responses. It was shown that chitotriosidase (chitinase 1/CHIT1) and structurally-related chitinase 3-like 1 protein (CHI3L1/YKL-40) play important roles in the pathobiology of idiopathic pulmonary fibrosis (IPF), however little is known about their longitudinal serum levels and relationship to clinical measures in IPF. Methods: The present study is the first to evaluate serial measurements of serum CHIT1 activity and YKL-40 concentrations in patients with IPF starting antifibrotic treatment and followed up for 24 months. In addition, baseline serum CHIT1 and YKL-40 were compared between patients with IPF and control subjects, and possible CHIT1 and YKL-40 relationships to longitudinal clinical assessments in IPF were explored. Results: Baseline serum CHIT1 activity and YKL-40 concentrations were significantly elevated in patients with IPF compared to control subjects and showed similar discriminatory ability in distinguishing IPF from controls. No significant differences between the median serum CHIT1 activity and YKL-40 concentration measured over a study follow-up were noted. We found significantly elevated baseline serum CHIT1 activity in the progressors compared with the stables in the first year, while significantly increased baseline serum CHIT1 activity was noted in the stables compared to the progressors in the second year. Additionally, we observed a significant negative correlation between a change in serum YKL-40 concentration and a change in forced vital capacity (FVC) % predicted (% pred.) in the stables subgroup, whereas, a change in serum CHIT1 activity correlated negatively with a change in FVC% pred. in the progressors subgroup. Conclusions: This explorative study findings add further evidence that CHIT1 and YKL-40 are upregulated in patients with IPF, and suggest that longitudinally stable serum CHIT1 activity and YKL-40 concentration levels may potentially be associated with the antifibrotic treatment response. In addition, our findings are supporting the possible role of CHIT1 and YKL-40 as candidate diagnostic and prognostic biomarkers in IPF. Further research is needed to validate present study findings. [ABSTRACT FROM AUTHOR]

Although current therapies in chronic obstructive pulmonary disease (COPD) improve the quality of life, they do not satisfactorily reduce disease progression or mortality. There are still many gaps in knowledge about the cellular, molecular, and genetic mechanisms contributing to pathobiology of this disease. However, increasing evidence suggests that accelerated aging, chronic systemic inflammation, and oxidative stress play major roles in pathogenesis in COPD, thus opening new opportunities in therapy. Therefore, the aim of our review was to describe and discuss some of the most widely used therapeutics that affect the root cause of aging and oxidative stress (metformin, melatonin, sirolimus, statins, vitamin D, and testosterone) in context of COPD therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal disease with a heterogeneous clinical course. This study aimed to evaluate the usefulness of circulating biomarkers in routine IPF clinical practice. We conducted an exploratory study in a cohort of 28 IPF subjects qualified for anti-fibrotic therapy with up to 24 months serial measurements of seven IPF biomarkers, including those that are well-established, Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), matrix metalloproteinase 7 (MMP-7), and more recently introduced ones, cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA-125), chemokine (C-C motif) ligand 18 (CCL18), and periostin. Among studied biomarkers, SP-D had the highest diagnostic accuracy to differentiate IPF subjects from controls, followed by MMP-7 and KL-6. At each study timepoint, KL-6 levels correlated inversely with forced vital capacity % predicted (FVC% pred.), and transfer factor of the lung for carbon monoxide % predicted (TL,CO% pred.), while SP-D levels correlated inversely with FVC% pred. and TL,CO% pred. at 24 months of anti-fibrotic therapy. Baseline KL-6 and CA19-9 concentrations were significantly elevated in patients with progressive disease in comparison to patients with stable disease. In addition, in the progressors subgroup CA19-9 concentrations significantly increased over the second year of study follow-up. In patients with progressive disease, we observed a significant inverse correlation between a change in SP-D levels and a change in FVC% pred. in the first year of treatment, whereas in the second year a significant inverse correlation between a change in KL-6 levels and a change in FVC% pred. was noted. Our study findings support the view that both well-established IPF biomarkers, including KL-6, SP-D, and MMP-7, and more recently introduced ones, like CA19-9, have the potential to support clinical practice in IPF. [ABSTRACT FROM AUTHOR]

Background: Recently, epithelial alarmins have been shown to play important roles in non-allergen driven respiratory diseases like idiopathic pulmonary fibrosis (IPF). Little is known about the expression of the epithelial alarmins in IPF. Methods: This study aimed to prospectively examine interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in the serum and exhaled breath condensate (EBC) in patients with IPF before and after one-year of antifibrotic treatment. A total of 82 volunteers, including 52 patients diagnosed with IPF that qualified for antifibrotic therapy as well as 30 controls, were examined. All study participants underwent baseline peripheral blood and EBC sampling. In 35 out of 52 IPF subjects, a follow-up sampling was performed after 12 months of antifibrotic treatment. Concentrations of alarmins in the serum and EBC were evaluated by means of ELISA. Results: Baseline TSLP concentrations were significantly elevated in patients with IPF compared to controls both in the serum (p < 0.05) and EBC (p < 0.0001). Baseline IL-25 and IL-33 serum and EBC levels did not differ significantly between IPF subjects and controls. Prospective analysis of changes in the epithelial alarmin levels showed significantly decreased IL-25 and TSLP EBC concentrations after 12 months of antifibrotic treatment (p < 0.05), which was observed in the subgroup of IPF patients treated with pirfenidone, but not in those treated with nintedanib. In stable patients with IPF over a study period (absolute forced vital capacity (FVC) % of predicted decline/year ≤ 5%, n = 25), a significant decrease in the EBC levels of both IL-25 and TSLP after 12 months of antifibrotic treatment was noted (p < 0.05), whereas, in progressor IPF patients (absolute FVC % of predicted decline/year > 5%, n = 10), a significant decrease was noted in the IL-25 EBC levels only (p < 0.05). Conclusions: Elevated TSLP levels in patients with IPF and their significant decrease in the lung compartment during antifibrotic therapy in stable patients with IPF, but not in progressors, support its significant contribution to pro-fibrotic type 2 immune responses in IPF. Noted changes in the epithelial alarmins concentration in the lung compartment during pirfenidone therapy may suggest its possible interaction with epithelial alarmins pathways in IPF. [ABSTRACT FROM AUTHOR]