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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.

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.

Idiopathic pulmonary fibrosis (IPF) is a condition which affects mainly older adults, that suggests mitochondrial dysfunction and oxidative stress, which follow cells senescence, and might contribute to the disease onset. We have assumed pathogenesis associated with crosstalk between the extracellular matrix (ECM) and mitochondria, mainly based on mitochondrial equilibrium impairment consisting of (1) tyrosine kinases and serine-threonine kinase (TKs and ST-Ks) activation via cytokines, (2) mitochondrial electron transport chain dysfunction and in consequence electrons leak with lower ATP synthesis, (3) the activation of latent TGF-β via αVβ6 integrin, (4) tensions transduction via α2β1 integrin, (5) inefficient mitophagy, and (6) stress inhibited biogenesis. Mitochondria dysfunction influences ECM composition and vice versa. Damaged mitochondria release mitochondrial reactive oxygen species (mtROS) and the mitochondrial DNA (mtDNA) to the microenvironment. Therefore, airway epithelial cells (AECs) undergo transition and secrete cytokines. Described factors initiate an inflammatory process with immunological enhancement. In consequence, local fibroblasts exposed to harmful conditions transform into myofibroblasts, produce ECM, and induce progression of fibrosis. In our review, we summarize numerous aspects of mitochondrial pathobiology, which seem to be involved in the pathogenesis of lung fibrosis. In addition, an increasing body of evidence suggests considering crosstalk between the ECM and mitochondria in this context. Moreover, mitochondria and ECM seem to be important players in the antifibrotic treatment of IPF.

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.

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.

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

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.

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

1. Introduction: 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.2. Materials and methods: 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 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 to 5 points) and Fatigue Assessment Scale weekly surveys were filled. We expected a drop of saturation during thromboembolic events, infectious complications, etc.3. Results: A total of 30 patients were monitored for a minimum period of 45 days, at least 2 weeks after spontaneous saturation normalization. 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 lower mean – 94 (93-96) % vs 96 (95-97)%, p=0.01 and minimum saturation – 89 (86-92)% vs. 92 (90-94)%, p=0.04. They also presented higher variations in saturation measurements; saturation amplitude was 9 (7-11)% vs 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. 4. Conclusions: 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 in 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.

(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.

BackgroundAlthough 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.MethodsThe 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.ResultsBaseline 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.ConclusionsThis 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.

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

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.

Interstitial lung diseases (ILDs) are a diverse group of disorders, which differ significantly with respect to aetiopathogenesis, clinical, radiological, and pathological picture. Idiopathic pulmonary fibrosis (IPF) and sarcoidosis represent two distinctive examples of ILDs [1]., 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

COPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism as the basis for modern therapy is important. The aim of the study was the assessment of gene expression levels, IL-6, IL-6ST, PIAS3, STAT3, and miRNAs, miRNA-1, miRNA-106b, miRNA-155, in patients with COPD. Induced sputum as well as PBMC were collected from 40 patients clinically verified according to the GOLD 2021 (A–D) classification and from the control group (n = 20). The levels of gene and miRNA expression were analysed by qPCR. In induced sputum IL6 was significantly down-regulated in COPD group compared with control (p = 0.0008), while IL6ST were up-regulated (p = 0.05). The results were also statistically significant for STAT3 (p = 0.04) and miRNA-155 (p = 0.03) with higher expression in the current smokers compared to ex-smokers. Higher expression levels for IL6ST (p = 0.03) in COPD patients with the exacerbation history compared to COPD patients without the exacerbation history were noted. Compared induced sputum and PB lymphocytes we observed higher expression of IL6 (p = 0.0003), STAT3 (p = 0.000001) miRNA-106b (p = 0.000069 and miRNA-155 (p = 0.000016) in induced sputum with lower expression of PIAS3 (p = 0.006), IL6ST (p = 0.002) and miRNA-1 (p = 0.001). Differences in gene expression levels of the IL-6/IL6ST/STAT3 pathway and miRNA depending on the smoking status and classification of patients according to GOLD suggest the importance of these genes in the pathogenesis of COPD and may indicate their potential utility in monitoring the course of the disease.

Background: Oral pirfenidone reduces lung function decline and mortality in idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects including nausea, rash, photosensitivity, weight loss, and fatigue. Dosage reductions in response to side effects may be suboptimal in slowing the rate of disease progression. This trial (ATLAS) assessed the safety, tolerability, and efficacy of pirfenidone solution for inhalation (AP01) in patients with IPF. Methods: This phase 1b randomized, open-label, dose-response trial is being performed at 25 sites in six countries (ANZCTR: ACTRN12618001838202). Patients diagnosed with IPF within 5 years, forced vital capacity (FVC) 40–90% predicted, and intolerant, unwilling, or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulized AP01 50 mg once daily (QD) or 100 mg twice daily (BID) for 48 weeks. The primary efficacy measure was absolute change in FVC % predicted. Findings: Participants were recruited between May 31, 2019, and April 30, 2020; of 141 IPF patients screened, 91 were enrolled (50 mg QD: n=46, 100 mg BID: n=45). Changes in FVC % predicted (95% CI) over 48 weeks, estimated as slopes, were −­5·3 (−8·0, −2·7) in the 50 mg QD and −0·5 (−3·3, 2·3) in the 100 mg BID groups (evaluable n=39 and 34, respectively); difference was 4·8 (1·0, 8·7); p=0·0152. The most common treatment-related adverse events (all mild to moderate) included cough (14, 15·4%), rash (11, 12·1%), nausea (8, 8·8%), throat irritation (5, 5·5%), dysgeusia and fatigue (4 each, 4·4%), and dizziness and dyspnoea (3 each, 3·3%). Interpretation: Mean FVC % predicted was stable in the 100 mg BID group, and FVC response was significantly better than in the 50 mg QD group. Nausea and rash side effects commonly associated with oral pirfenidone were less frequent with AP01. Further study of AP01 is warranted. Trial Registration: This phase 1b randomized, open-label, dose-response trial is being performed at 25 sites in six countries (ANZCTR: ACTRN12618001838202). Funding: Avalyn Pharma Declaration of Interest: MLS, DN, LF, KO, and ABM are all employees of the sponsor, Avalyn Pharma. Authors AGW, AB, MLWilsher, PH, MS, and WP report no conflicts of interest. NC received a grant from Boehringer Ingelheim and consulting fees from Boehringer Ingelheim, Carrick, Carrick, Redex, UCB, and Novartis; speaker fees and travel sponsorship from Boehringer Ingelheim and Roche; and payment for participation on data safety monitoring/advisory board from Boehringer Ingelheim. IG reports consulting fees from Amplia, Ad Alta, and Accendatech; speaking fees from Boehringer Ingelheim; and payment for participation in a safety review committee from Accendatech. TJC reports receiving grants/contracts from Boehringer Ingelheim, Roche, Bristol Myers Squibb, Biogen, Galapagos, and Avalyn Pharma; speaker’s honoraria from Boehringer Ingelheim and Roche; and payment for participation on data safety monitoring/advisory board from Boehringer Ingelheim, Roche, Bristol Myers Squibb, and Promedior. EJ received honoraria for lectures from Boehringer Ingelheim, Roche, AstraZeneca, MDS, Chiesi; sponsored travel to meetings from Boehringer Ingelheim and Roche; and payment for participation in advisory boards from Boehringer Ingelheim, Roche, AstraZeneca, Novartis, MDS, Berlin-Chemie, and Chiesi. MWijsenbeek reports payments to her institution from Boehringer Ingelheim, Roche, the Netherlands Organisation for Health Research and Development, the Dutch Lung Foundation, the Dutch Pulmonary Fibrosis Patient Association, the Thorax Foundation, ErasmusMC, and Sarcoidoisis.nl. Consulting fees were paid to her institution by Boehringer Ingelheim, Roche, Galapagos, Bristol Myers Squibb, Galecto, and Respivant; honoraria were paid to her institution by Boehringer Ingelheim, Roche, and Novartis. MWijsenbeek received sponsored travel from Boehringer Ingelheim and Roche, and her institution received payment for her participation in data safety monitoring/advisory board from Savara and Galapagos. CG received consulting fees from Avalyn Pharma. GR reports receiving support from Avalyn Pharma for consulting and for chairing the Data Safety Monitoring Board during the conduct of the study; personal and consulting fees from Boehringer Ingelheim, Respivant, and Roche; grants from the NIH; and consulting fees from Bellerophon Therapeutics, Biogen, Bristol Myers Squibb, Fibrogen, Nitto, Promedior, Respivant, and Veracyte. Ethical Approval: The trial was approved by local ethics committees, and all patients provided written informed consent before trial entry.

Air pollution is a major environmental risk to health and a global public health concern. In 2016, according to the World Health Organization (WHO), ambient air pollution in cities and rural areas was estimated to cause 4.2 million premature deaths. It is estimated that around 91% of the world’s population lives in places where air pollution exceeds the limits recommended by the WHO. Sources of air pollution are multiple and context-specific. Air pollution exposures are established risk factors for development and adverse health outcomes in many respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), or lung cancer. However, possible associations between air pollution and idiopathic pulmonary fibrosis (IPF) have not been adequately studied and air pollution seems to be an underrecognized risk factor for IPF. This narrative review describes potential mechanisms triggered by ambient air pollution and their possible roles in the initiation of the pathogenic process and adverse health effects in IPF. Additionally, we summarize the most current research evidence from the clinical studies supporting links between air pollution and IPF.

At the end of the last century, genetic studies reported that genetic information is not transmitted solely by DNA, but is also transmitted by other mechanisms, named as epigenetics. The well-described epigenetic mechanisms include DNA methylation, biochemical modifications of histones, and microRNAs. The role of altered epigenetics in the biology of various fibrotic diseases is well-established, and recent advances demonstrate its importance in the pathogenesis of pulmonary fibrosis-predominantly referring to idiopathic pulmonary fibrosis, the most lethal of the interstitial lung diseases. The deficiency in effective medications suggests an urgent need to better understand the underlying pathobiology. This review summarizes the current knowledge concerning epigenetic changes in pulmonary fibrosis and associations of these changes with several cellular pathways of known significance in its pathogenesis. It also designates the most promising substances for further research that may bring us closer to new therapeutic options.

Introduction and Aim: Sarcoidosis is widely considered to be a disease with dominant Th1 response. However, results of several recent studies suggested similar prevalence of Th2-dominant allergic diseases in patients with sarcoidosis and general population. The aim of our study was to assess the occurrence of atopic disorders in patients with sarcoidosis and compare it with local population. Material and Methods: We created a questionnaire focusing on sarcoidosis and allergy and surveyed all adults treated for sarcoidosis in our tertiary pulmonary clinic. We combined the results with our medical records to create a comprehensive database for statistical analysis. We compared the results with previously published local data of the ECAP study (Epidemiology of the Allergic Diseases in Poland). Results: Among 329 adults who answered the survey, 114 (34%) reported at least 1 allergic disease. Asthma, atopic dermatitis and food allergy rates were similar to those of local population reported in epidemiological data (11,9% vs 9%, 2,7% vs 4% and 4,9% vs 5,0%, respectively). Urticaria was more frequent in sarcoidosis patients (15,5% vs 8%) and allergic rhinitis was nearly 3 times less common (11,5 vs 30%). Interestingly, within surveyed group, asthmatics reported more severe sarcoidosis symptoms and all patients with atopic diseases were more likely to report seasonal fluctuations in their perception of sarcoidosis symptoms, compared to those with no allergic disorders (23% vs 7%, respectively, p Conclusions: Prevalence of allergy among sarcoidosis patients is lower than in general population, but patients with allergic diseases tend be more symptomatic and perceive their sarcoidosis as more severe.

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.

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

Electronic cigarette (e-cigarette) use is one of the most popular alternatives to conventional cigarette smoking. This study aimed to investigate the prevalence of cigarette and e-cigarette use among university students from Poland, with particular emphasis on ever and current cigarette and e-cigarette use as well as smoking initiation age.A cross-sectional survey was conducted between 2017 and 2018 in a group of university students in 5 academic centers in Poland. The questionnaire addressed 46 questions about personal attitudes toward cigarette smoking and e-cigarette use.Data were collected from 7324 participants (67.3% females, aged 21.9 ± 2.1 years), with an overall response rate of 70.1%. Among participants, 71.2% had ever smoked a cigarette, and almost half of the respondents (45%) declared ever use of an e-cigarette. The mean age of first use of a cigarette was significantly lower (16.5 ± 2.5 y-old) than of an e-cigarette (18.6 ± 2.2 y-old; p 0.001). Exclusive cigarette smoking was declared by 12.9%, 1.3% were e-cigarette users and 1.5% were dual users. Those in the medical field were less likely to try e-cigarettes (odds ratio, OR = 0.73) or to currently smoke conventional cigarettes (OR = 0.82). Older participants were more likely to have ever smoked conventional cigarettes (OR = 1.06), but less likely to have ever used e-cigarettes (OR = 0.88).In this study, we found a high proportion of young adults who have tried e-cigarettes with both regional and demographic differences. The education profile influences cigarette smoking and e-cigarette use behaviors.

Background Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles. Methods This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion. Results A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75–30) months and from diagnosis to start of pirfenidone treatment was 6 (2–23) months. Patients were followed on treatment for a median of 17 (12–22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient’s own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was −20 ml (−200–100) and during the second year was −120 ml (−340–30). Over a study period, 33 patients (10.75%) died. Conclusions The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.

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

Joanna Miłkowska-Dymanowska,1,2,* Adam J Białas,1,2,* Karolina Szewczyk,1 Zofia Kurmanowska,1 Paweł Górski,1,2 Wojciech J Piotrowski1,2 1Department of Pneumology and Allergy, Medical University of Łódź, Łódź, Poland; 2Healthy Ageing Research Centre, Medical University of Łódź, Łódź, Poland *These authors contributed equally to this work Introduction: Exacerbations of COPD (ECOPDs) are important events in the course of COPD, accelerating the rate of decline in lung function and increasing the mortality risk. A growing body of evidence suggests the significance of the “frequent exacerbator” phenotype. This phenotype seems to be associated with a more severe airflow limitation, symptoms, health-related quality of life impairment, and higher mortality. However, there is no described biomarker that would help to identify this group of patients. Patients and methods: Patients with COPD in “D” GOLD category were monitored for 3years according to events of ECOPD. Serum samples were collected from the patients. Circulating level of plasma soluble receptor for advanced glycation end-products (sRAGE) was measured using commercially available high sensitivity kits. The receiver operating characteristic (ROC) curve analysis was used to assess the usefulness of sRAGE to identify frequent exacerbator phenotype. Log-rank test was used in the analysis of time to the subsequent exacerbation. Pearson (R) or Spearman’s rank (RS) correlation coefficients were used for correlation analysis. Results: Nineteen patients were enrolled. The area under the ROC curve (AUROC) for sRAGE for the identification of frequent exacerbator phenotype was 0.81. Analysis identified the cutoff point as 850.407pg/mL, characterized by a sensitivity of 0.80 (95% CI: 0.28–1.0) and specificity of 0.93 (95% CI: 0.66–1.0). Additionally, in the group with sRAGE ≤850.407 pg/mL, we observed significantly shorter time to the subsequent exacerbation: median of 32 vs 105.5days (P=0.03). Correlation analysis revealed significant negative correlation between sRAGE and the number of exacerbations requiring hospitalization during the whole time of follow-up (RS=-0.53; P=0.02) and significant positive correlation with FEV1 expressed as the percentage of reference value (R=0.6; P=0.006). Conclusion: sRAGE seems to be useful in the identification of frequent exacerbator phenotype. This parameter may also be used in the prediction of time to ECOPD. Our findings should be confirmed in a sufficiently powered larger sample. Keywords: sRAGE, frequent exacerbator phenotype of COPD, exacerbations of COPD, COPD, prediction of AECOPD

Introduction: Fiber-optic bronchoscopy (FOB) is commonly performed in the first line in diagnostic process of haemoptysis. However, lots of evidences suggest that in haemoptysis FOB do not always provide additional, useful information to radiological diagnostics. Therefore, this study aimed to evaluate the validity of performing FOB as a method of choice in first line diagnostics of haemoptysis. Material and methods: Data comprised consecutively collected results from patients referred for FOB assessment for clinical purposes were retrospectively analysed. We included all examinations, which were performed due to haemoptysis as the only indication, excluding any other lung-related conditions. Results: 114 patients were finally included to the study. The median age was 59 (IQR: 46–64.75). Active bleeding was visualized during examination of 13 (11.4%) patients. Patients with active bleeding did not differ significantly according to age: 59 (54–69) vs. 59 (45–64) years; W = 532.5, p-value = 0.27, and gender: c2 = 1.68, p-value = 0.2. On the other hand, in 29 (25.44%) patients, FOB revealed no visible abnormalities. This subgroup of patients was significantly younger — 46 (34–62) years vs. 60 (53–67) years; W = 782, p-value = 0.003. Conclusion: Low number of visualized active bleeding sites suggest overuse of bronchoscopy in diagnosis of haemoptysis. Indications for this examination should be reconsidered especially in young patients with non-massive haemoptysis.

Kyphoscoliosis is a significant clinical problem with no precise Guideliness for management, especially concerning respiratory pathology. No exhaustive systematic review has yet been performed. The aim was to conduct a systematic review of available data concerning the pathophysiology and treatment of kyphoscoliosis. An electronic systematic search compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guideliness was conducted. The Pubmed database was examined and the search was updated to November 10, 2016. In total, 188 articles were screened, and 52 full text articles were then assessed for eligibility. As 24 of them met exclusion criteria, only 28 articles were further analysed. These articles were published in 18 journals from 1959 to 2015, with 25 being original studies, and one randomised control trial. The total corpus included 18 prospective studies, 7 retrospective studies and 3 Case Reports. KS is a significant complex, multidisciplinary clinical problem. The heterogeneous nature of the majority of published studies prevents unequivocal conclusions being drawn. Despite a great progress in knowledge about the respiratory system functioning and pathology in KS, the treatment seems to be not yet quite yet satisfactory. Therefore, there is a strong need for large prospective studies and unified clinical Guideliness in on the management of this group of patients.

Sebastian Majewski,1,2 Anna Pietrzak,3 Damian Tworek,4 Karolina Szewczyk,5 Anna Kumor-Kisielewska,1 Zofia Kurmanowska,5 Paweł Górski,1,2 Anna Zalewska-Janowska,3,* Wojciech Jerzy Piotrowski1,2,* 1Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland; 2Healthy Ageing Research Centre (HARC), Lodz, Poland; 3Department of Psychodermatology, Medical University of Lodz, Lodz, Poland; 4Department of General and Oncological Pulmonology, Medical University of Lodz, Lodz, Poland; 5Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland *These authors contributed equally to this work Background: The systemic (extrapulmonary) effects and comorbidities of chronic obstructive pulmonary disease (COPD) contribute substantially to its burden. The supposed link between COPD and its systemic effects on distal organs could be due to the low-grade systemic inflammation. The aim of this study was to investigate whether the systemic inflammation may influence the skin condition in COPD patients. Materials and methods: Forty patients with confirmed diagnosis of COPD and a control group consisting of 30 healthy smokers and 20 healthy never-smokers were studied. Transepidermal water loss, stratum corneum hydration, skin sebum content, melanin index, erythema index, and skin temperature were measured with worldwide-acknowledged biophysical measuring methods at the volar forearm of all participants using a multifunctional skin physiology monitor. Biomarkers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), were measured in serum using commercially available enzyme-linked immunosorbent assays. Results: There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level (P

Adam J Białas,1,2,* Claudio Pedone,3,* Wojciech J Piotrowski,1,2 Raffaele Antonelli Incalzi3 1Department of Pneumology and Allergy, Medical University of Lodz, Łódź, Poland; 2Healthy Aging Research Centre (HARC), Medical University of Lodz, Łódź, Poland; 3Department of Geriatrics, Campus Bio-Medico University of Rome, Rome, Italy *These authors contributed equally to this work Background: Platelets may actively participate in inflammation in COPD. Platelet distribution width (PDW), a measure of platelets’ volume heterogeneity, may increase in platelets’ activation. We hypothesized that PDW may be a marker of hypercoagulation, which plays a significant role in conditions associated with worse survival of patients with COPD, eg, acute myocardial infarction and other forms of ischemic heart disease.Methods: Retrospective analysis of 79 patients. Variables were compared after grouping patients according to the upper normal limit of PDW, using Welch’s t-tests or Mann–Whitney U, and chi-square tests. Survival in the two groups was compared using the Kaplan–Meier method and Cox proportional hazards regression.Results: Ten patients presented values of PDW above 16 fL, which was the upper limit of normality for our laboratory. Compared to patients with normal PDW, they had lower forced expiratory flow between 25% and 75% of vital capacity (FEF 25–75) – 35% of reference value vs 57% (P=0.003) and peak expiratory flow – 39% vs 54% (P

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

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 &lt, 0.05) and EBC (p &lt, 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 &lt, 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 &le, 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 &lt, 0.05), whereas, in progressor IPF patients (absolute FVC % of predicted decline/year &gt, 5%, n = 10), a significant decrease was noted in the IL-25 EBC levels only (p &lt, 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.

Pulmonary Langerhans’ cell histiocytosis (PLCH) is a neoplastic disorder with strong inflammatory component. The clinical manifestations, features, and outcome of the PLCH vary widely, and clinical course of the disease is unpredictable. Material and methods: 124 adults (61 women and 63 men in age 15 to 69 years) with LCH, have been presented in our Department for the last 21 years. The median follow-up period was 146 months (range 3 to 338 months). Results: Isolated PLCH was diagnosed in 90(72%) cases, multisystem disease in 30(26%) patients. Two (1.6%) patients had multifocal bone disease, one (0.8%) had isolated mucosal, and one isolated bone lesion. Out of whole group only 6(5%) patients were nonsmokers. Incidentally the disease was diagnosed in 20% of patients. Pneumothorax as a first symptom of the disease was observed in 26% of patients. The most common findings in the pulmonary function tests were obstructive ventilatory defect (57%), and decreasing of transfer factor for carbon monoxide (80%). During the time of observation 70(56%) patients did not require immunosuppressive therapy. Only in 3(14%) patients steroid treatment was sufficient, other 19(86%) patients required chemotherapy. Chemotherapy with vinblastine, prednisone and mercaptopurine was administered in 11 patients, but only in 4 the regression with non-active disease was observed. Sixteen (13%) patients were treated successfully with cladribine, and till now no relapse was noticed. Conclusions: PLCH is a rare, cystic lung disease, affects mainly young adult smokers, without gender predominance; early diagnosis, smoking cessation, and adequate treatment are critical in its management.

Sebastian Majewski,1 Damian Tworek,2 Karolina Szewczyk,1 Justyna Kiszałkiewicz,3 Zofia Kurmanowska,1 Ewa Brzeziańska-Lasota,3 Hanna Jerczyńska,4 Adam Antczak,2 Wojciech Jerzy Piotrowski,1 Paweł Górski11Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland; 2Department of General and Oncological Pulmonology, Medical University of Lodz, Lodz, Poland; 3Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland; 4Central Scientific Laboratory (CoreLab), Medical University of Lodz, Lodz, PolandBackground: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown.Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD.Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated.Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P