Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

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.

Primary pulmonary Hodgkin's lymphoma mimicking granulomatosis with polyangiitis - a case report of diagnostic and therapeutic dilemmas.

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.

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.

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.

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.

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.

The utility of telemedicine in managing patients after COVID-19.

Despite growing knowledge about transmission and relatively wide access to prophylaxis, the world is still facing a severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) global pandemic. Under these circumstances telemedicine emerges as a powerful tool for safe at-home surveillance after a hospital discharge; the data on when to safely release a patient after acute COVID-19 is scarce. Reckoning an urgent need for improving outpatient management and possibly fatal complications of the post-COVID period, we performed the pilot telemonitoring program described below. The study aimed to assess the usefulness of parameters and surveys remotely obtained from COVID-19 convalescents in their individual prognosis prediction. Patients were involved in the study between December 2020 and May 2021. Recruitment was performed either during the hospital discharge (those hospitalized in a Barlicki Memorial Hospital in Lodz) or the first outpatient visit up to 6 weeks after discharge from another center. Every participant received equipment for daily saturation and heart rate measurement coupled with a tablet for remote data transmission. The measurements were made after at least fifteen minutes of rest in a sitting position without oxygen supplementation. Along with the measurements, the cough and dyspnea daily surveys (1-5 points) and Fatigue Assessment Scale weekly surveys were filled. We expected a saturation decrease during thromboembolic events, infectious complications, etc. A total of 30 patients were monitored for a minimum period of 45 days, at least 2 weeks after spontaneous saturation normalization. The mean age was 55 (mean 55.23; SD ± 10.64 years). The group was divided according to clinical improvement defined as the ≥ 10% functional vital capacity (FVC) raise or ≥ 15% lung transfer for carbon monoxide (TL,CO) rise. Our findings suggest that at-rest home saturation measurements below 94% (p = 0.03) correspond with the lack of clinical improvement in post-COVID observation (p = 0.03). The non-improvement group presented with a lower mean-94 (93-96)% versus 96 (95-97)%, p = 0.01 and minimum saturation-89 (86-92)% versus 92 (90-94)%, p = 0.04. They also presented higher variations in saturation measurements; saturation amplitude was 9 (7-11)% versus 7 (4-8)%, p = 0.03; up to day 22 most of the saturation differences reached statistical significance. Last but not least, we discovered that participants missing 2 or more measurements during the observation were more often ranked into the clinical improvement group (p = 0.01). Heart rate day-to-day measurements did not differ between both groups; gathered data about dyspnea and cough intensity did not reach statistical significance either. A better understanding of the disease's natural history will ultimately lead us to a better understanding of long COVID symptoms and corresponding threats. In this paper, we have found home oxygen saturation telemonitoring to be useful in the prediction of the trajectory of the disease course. Our findings suggest that detection of at-rest home saturation measurement equal to or below 94% corresponds with the lack of clinical improvement at the time of observation and this group of patients presented higher variability of day-to-day oxygen saturation measurements. The determination of which patient should be involved in telemedicine programs after discharge requests further research.

Guidelines of the Polish Respiratory Society on the Diagnosis and Treatment of Progressive Fibrosing Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis.

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

Guidelines of the Polish Respiratory Society on the Diagnosis and Treatment of Progressive Fibrosing Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

Isolated Severe Dysphonia as a Presentation of Post-COVID-19 Syndrome.

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.

Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis.

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.

Serial Measurements of Circulating KL-6, SP-D, MMP-7, CA19-9, CA-125, CCL18, and Periostin in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Therapy: An Exploratory Study.

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.

Gender differences in health-related quality of life measured by the Sarcoidosis Health Questionnaire.

Sarcoidosis is granulomatous disease, which complex etiology is yet to be fully discovered. In the majority of cases its course is self-limiting. However it can have different clinical manifestations and can be debilitating condition with great impact on health-related quality of life (HRQL). The aim of our study was to assess if there are any differences in HRQL dependent to gender. We examined a group of 33 males and 42 females (with no differences in mean age, disease activity, TLCO, FEV1, FVC, FEV1/FVC) with a use of Sarcoidosis Health Questionnaire. We revealed lower total and daily functioning score in female group. Further analyses stratified by sex and activity of the disease presented many significant differences between the groups, revealing important issues for the discussion about gender specific differences in the HRQL of patients with sarcoidosis. In spite of clinical presentation may be similar, expectations and main concerns of sarcoidosis patient can vary between females and males. Therefore, it appears that in terms of education and symptomatic treatment accents should be put differently depending on the gender of the patient. Our results may also point to a need for more gender-oriented patient-physician communication which could enable better understanding, potentially improve adherence to therapy and decrease the risk of possible complications.

Proteomic profiling of peripheral blood and bronchoalveolar lavage fluid in interstitial lung diseases: an explorative study.

Proximity extension assay proves feasible for multiplex analysis of proteins in bronchoalveolar lavage. Small exploratory study found multiple inflammatory proteins that differed between patients with sarcoidosis and idiopathic pulmonary fibrosis. https://bit.ly/3nW14nF.

The prognostic value of fixed time and self-paced walking tests in patients diagnosed with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia that has an unknown etiology. The natural history of the disease is characterized by a progressive decline in pulmonary function and overall health and well-being. The median survival time is between 2-3 years; however, the disease course is variable and unpredictable. The twelve-minute walking test (12MWT) and six-minute walking test (6MWT) are two fixed time tests that are commonly used in clinical practice. Our short and clinically oriented narrative review attempted to summarize current evidence supporting the use of fixed time, self-paced walking tests in predicting the outcome of patients diagnosed with IPF. A number of studies have justified that the 6MWT is a simple, cost-effective, well documented, fixed time, and self-paced walking test which is a valid and reliable measure of disease status and can also be used as a prognostic tool in patients with IPF. However, there is a need for dedicated and validated reference equations for this population of patients. It is also necessary to fill the knowledge gap about the role of the 12MWT. We hypothesize that it would be useful in evaluating patients that are in the early stages of the disease.

Eosinopenia and neutrophil-to-lymphocyte count ratio as prognostic factors in exacerbation of COPD.

Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPDs) are one of the most important clinical aspects of the disease, and when requiring hospital admission, they significantly contribute to mortality among COPD patients. Our aim was to assess the role of eosinopenia and neutrophil-to-lymphocyte count (NLR) as markers of in-hospital mortality and length of hospitalization (LoH) among patients with ECOPD requiring hospitalization. We included 275 patients. Eosinopenia was associated with in-hospital deaths only when coexisted with lymphocytopenia, with the specificity of 84.4% (95% CI 79.6-88.6%) and the sensitivity of 100% (95% CI 35.9-100%). Also, survivors presented longer LoH (P < 0.0001). NLR ≥ 13.2 predicted in-hospital death with the sensitivity of 100% (95% CI 35.9-100%) and specificity of 92.6% (95% CI 88.8-95.4%), however, comparison of LoH among survivors did not reach statistical significance (P = 0.05). Additionally, when we assessed the presence of coexistence of eosinopenia and lymphocytopenia first, and then apply NLR, sensitivity and specificity in prediction of in-hospital death was 100% (95% CI 35.9-100) and 93.7% (95% CI 90.1-96.3), respectively. Moreover, among survivors, the occurrence of such pattern was associated with significantly longer LoH: 11 (7-14) vs 7 (5-10) days (P = 0.01). The best profile of sensitivity and specificity in the prediction of in-hospital mortality in ECOPD can be obtained by combined analysis of coexistence of eosinopenia and lymphocytopenia with elevated NLR. The occurrence of a such pattern is also associated with significantly longer LoH among survivors.

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.

The role of bronchoscopy in diagnosis of chronic cough in adults: a retrospective single-center study.

INTRODUCTION: Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional testing of samples collected during FOB in the differential diagnosis of chronic cough in adults. MATERIAL AND METHODS: This was a single-center retrospective study. Out of 7115 conventional white light FOB examinations, we finally selected 198 with cough as the only indication. RESULTS: In 40.9% of bronchoscopic examinations, no visible cause of cough was found. Visual signs of chronic bronchitis (CB) were detected in 57.6% of reports. Only in 3 cases (1.5%) bronchoscopy revealed a potential cause of chronic cough other than CB. Mycobacterium tuberculosis or other mycobacteria were spotted in none of the samples. In 91.1% of bronchoalveolar lavage (BAL) cytologic examinations, at least one cell count abnormality was detected, but only in case of increased percentage of eosinophils, it might be considered clinically relevant. In 53% of bacteriological culture results, at least one potentially pathogenic bacterium was isolated. CONCLUSIONS: The present study results strengthen the evidence that FOB combined with additional testing of airway specimens obtained during FOB is not a powerful tool in the differential diagnosis of chronic cough, and FOB as a diagnostic tool may be overused. The appropriate timing and decision regarding referral for FOB and additional testing of achieved material requires careful clinical consideration.