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Background Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW P P P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (P = 0.01)]. Conclusions Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Interstitial lung diseases (ILDs) cover a wide heterogeneous group of disorders, both of unknown and known causes. Accurate diagnosis is essential but, at the same time, presents many challenges. Typically, the distinction between idiopathic pulmonary fibrosis and fibrotic hypersensitivity pneumonitis (HP) can prove extremely difficult. However, another major, but underestimated, challenge is the diagnosis of connective tissue disease-associated ILD (CTD-ILD), specifically when ILD is the initial manifestation or when extrapulmonary manifestations are subclinical. Antisynthetase syndrome (ASyS) is a characteristic example where lung involvement can be the predominant feature in the absence of other evidence suggestive of CTD. In ASyS, lung involvement can be the initial manifestation or muscle involvement can be subclinical with normal muscle enzymes. Furthermore, a negative antinuclear antibody test does not indicate autoantibody negativity in the context of ASyS. Imaging and pathology findings in ASyS are not specific and overlap with other ILDs. Finally, bronchoalveolar lavage can exhibit pronounced lymphocytosis (>30–40%). The latter, in combination with a history of exposure to an inciting antigen, can lead to an erroneous diagnosis of HP with obvious negative impact on patients’ outcome. Herein, we report 3 female patients aged 61, 65, and 70 years and 1 male patient aged 43 years, with ASyS masquerading as HP and analyze the underlying reasons of misdiagnosis, aiming to raise awareness of the need for close collaboration between pulmonologists and rheumatologists.

Case Presentation A 77-year-old woman was referred to our interstitial lung disease unit. She presented with a history of progressive dyspnea on exertion and nonproductive, persistent cough over the previous year. She was diagnosed with Sjogren syndrome two years ago by a rheumatologist. In the context of Sjogren syndrome, she reported chronic xerostomia and xerophthalmia for the last 5 years. Her history was also notable for the presence of arterial hypertension and hypothyroidism. She denied the presence of shortness of breath, chest pain, arthralgia, muscle weakness, weight loss, night sweats, and fatigue. She reported exposure to house mold. There was no family history of respiratory diseases. The patient never smoked and denied alcohol consumption, illicit drug use, or any occupational exposures.

High-Resolution Computed Tomography (HRCT) plays a pivotal role in the diagnosis of Idiopathic Pulmonary Fibrosis (IPF). First, it establishes the presence of lung fibrosis. Second, it allows the recognition of specific patterns, namely typical and probable Usual Interstitial Pneumonia (UIP) pattern obviating the need for tissue confirmation in the appropriate clinical context.Acknowledging the extreme versatility of modern radiology and the heavy burden of knowledge the modern radiologist has to cope with, this review addresses the diagnostic pitfalls of honeycombing in IPF diagnosis. This review focuses on two areas: i) when honeycombing is actually present but there are other findings that should raise suspicion of an alternative diagnosis and ii) when honeycombing is misdiagnosed, focusing on the commonest radiographic patterns that are responsible for this confusion.It is pivotal to establish the actual presence of honeycombing. Even then, the distribution of honeycombing or the presence of other findings could be suggestive of alternative diagnoses. Reviewing older images can be extremely helpful in reaching the correct diagnosis.

The 2019 coronavirus disease (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected virtually all aspects of patient care. Healthcare systems around the world are trying to simultaneously treat patients with COVID-19 infection, prepare for its long-term impacts, and manage patients with other acute and chronic diseases. There are multiple ways that the COVID-19 pandemic will directly affect patients with fibrotic interstitial lung disease (ILD), particularly given their common risk factors for poor outcomes. Major issues for patients with ILD will include restricted access to key components of the diagnostic process, new uncertainties in the use of common ILD pharmacotherapies, limited ability to monitor both disease severity and the presence of medication adverse effects, and significantly curtailed research activities. The purpose of this review is to summarize how COVID-19 has impacted key components of the diagnosis and management of fibrotic ILD as well as to provide strategies to mitigate these challenges. We further review major obstacles for researchers and identify priority areas for future ILD research related to COVID-19. Our goals are to provide practical considerations to support the care of patients with ILD during the COVID-19 pandemic and to provide a road map for clinicians caring for these patients during future infectious disease outbreaks.

Immune checkpoint inhibitors are novel agents that have been proved efficacious in a variety of cancer types, but they are associated with a unique set of organ-specific, immune-related adverse events. Among them, immune-related pneumonitis requires special attention because it is difficult to diagnose and potentially lethal. Accumulating real-world epidemiological data suggest that immune-related pneumonitis is more frequent than previously reported. Its diagnosis requires exclusion of other causes and assessment of radiographic features on high-resolution CT of the chest. Management of immune-related pneumonitis is based on the use of immunosuppressants. Future research should be focused on finding predictive biomarkers for immune-related pneumonitis as well as optimizing its management.

Abundant epidemiologic evidence supports an association between idiopathic pulmonary fibrosis (IPF) and lung cancer. Lung tumors in patients with IPF develop preferentially in the periphery immediately adjacent to fibrotic areas, with different histologic distribution and immunohistochemical features compared with non-IPF-associated lung tumors. In this context, evidence indicates that IPF and lung cancer share many pathogenic similarities including genetic and epigenetic markers. It has been suggested that specific germline mutations predispose toward both IPF and lung cancer, leading to imbalance between oncogenes and tumor suppressor genes and ultimately carcinogenesis within fibrotic lungs. Aberrant epigenetic regulation due to methylation, histone modifications, and mainly deregulation of common noncoding RNAs represents a possible pathogenic link between the two disease paradigms. Genetic and epigenetic alterations lead to abnormal activation of common transduction pathways, including Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B, mediating metaplasia and hyperproliferation in alveolar type II epithelial cells. Cellular transformations in the mesenchymal phenotype represent a common link between lung fibrosis and carcinogenesis. In this review we summarize current data on common cellular and molecular pathogenic mechanisms between IPF and lung cancer and highlight promising therapeutic targets for this disease combination.

Case Presentation A 63-year-old woman presented with a 2-year history of nonproductive cough. She denied the presence of shortness of breath, chest pain, arthralgia, muscle weakness, weight loss, night sweats, and fatigue. She was a never smoker and had a history of arterial hypertension and diabetes. There was no history of asthma, allergic rhinitis, nasal polyps, or gastroesophageal reflux disease, known malignancy, or collagen tissue disease. She reported exposure to house mold. There was no family history of respiratory diseases. The patient denied alcohol consumption, illicit drug use, occupational exposures, any recent travel, or exposure to TB.

Airway distensibility measurement indices might be useful for providing additional information in detecting airway wall pathology in asthmahttps://bit.ly/3ntNLya

Introduction: Treatment of interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) often includes systemic corticosteroids. Use of steroid-sparing agents is amenable to avoid potential side effects. Methods: Functional indices and high-resolution computed tomography (HRCT) patterns of patients with non-IPF ILDs receiving mycophenolate mofetil (MMF) with a minimum follow-up of 1 year were analyzed. Two independent radiologists and a machine learning software system (Imbio 1.4.2.) evaluated HRCT patterns. Results: Fifty-five (n = 55) patients were included in the analysis (male: 30 [55%], median age: 65.0 [95% CI: 59.7–70.0], mean forced vital capacity %predicted [FVC %pred.] ± standard deviation [SD]: 69.4 ± 18.3, mean diffusing capacity of lung for carbon monoxide %pred. ± SD: 40.8 ± 14.3, hypersensitivity pneumonitis: 26, connective tissue disease-ILDs [CTD-ILDs]: 22, other ILDs: 7). There was no significant difference in mean FVC %pred. post-6 months (1.59 ± 2.04) and 1 year (−0.39 ± 2.49) of treatment compared to baseline. Radiographic evaluation showed no significant difference between baseline and post-1 year %ground glass opacities (20.0 [95% CI: 14.4–30.0] vs. 20.0 [95% CI: 14.4–25.6]) and %reticulation (5.0 [95% CI: 2.0–15.6] vs. 7.5 [95% CI: 2.0–17.5]). A similar performance between expert radiologists and Imbio software analysis was observed in assessing ground glass opacities (intraclass correlation coefficient [ICC] = 0.73) and reticulation (ICC = 0.88). Fourteen patients (25.5%) reported at least one side effect and 8 patients (14.5%) switched to antifibrotics due to disease progression. Conclusion: Our data suggest that MMF is a safe and effective steroid-sparing agent leading to disease stabilization in a proportion of patients with non-IPF ILDs. Machine learning software systems may exhibit similar performance to specialist radiologists and represent fruitful diagnostic and prognostic tools.

Case Presentation A 58-year-old woman was referred to our department with a cough of 1 year duration; her condition was unresponsive to the administration of inhaled steroid and beta-2 agonists. She denied the presence of dyspnea, chest pain, or other extrapulmonary symptoms. She was a never-smoker with a negative medical history and no occupational or domestic exposures. There was no history of cancer, gastroesophageal reflux disease, asthma, allergic rhinitis, or other allergies.

Background Fibrotic hypersensitivity pneumonitis (f-HP) can exhibit a progressive course similar to idiopathic pulmonary fibrosis (IPF). The lack of diagnostic guidelines and randomised controlled trials in this population represent a significant unmet need. Objectives To describe our clinical experience with antifibrotics in patients with f-HP. Material and methods Retrospective study of 30 patients diagnosed with f-HP upon re-evaluation within a multidisciplinary team discussion of 295 consecutive patients (January 2012 to December 2017) who had been diagnosed initially with IPF at outside facilities and were referred to our centres. Results Pirfenidone was initially administered to 14 (46.7%) patients and nintedanib to 16 (53.3%) patients. There were 26 (86.7%) males, with mean±sd age 70.2±8.4 years. The annual rate of decline in forced vital capacity (FVC) % predicted over the 3-year treatment period adjusted for baseline FVC % pred measurement was 4.2% (95% CI 1.9–6.6%, p=0.001) and 7.5% (95% CI 3.3–11.7%; p=0.001) in imputation analysis. The annual rate of decline in diffusing capacity of the lung for carbon monoxide (DLCO) % predicted throughout the 3-year treatment period adjusted for baseline DLCO % pred was 5.7% (95% CI 3.1–8.4%, p, In patients with fibrotic hypersensitivity pneumonitis receiving antifibrotics, there is a statistically significant annual decline in FVC % predicted and DLCO % predicted over a period of 3 years. Prospective randomised trials exceeding 1 year are needed. https://bit.ly/3abhAL9

Background: Telomere-related genes (TRG) mutations are detected in 30% of familial pulmonary fibrosis (FPF) and are also associated with personal/familial extra-pulmonary disease suggestive of short telomere syndrome (STS). Aim: to evaluate the prevalence of TRG mutations in a national cohort of interstitial lung disease (ILD) with suspected genetic predisposition in Greece and to define patients’ characteristics and impact on outcome.Methods: Genetic diagnoses made between December 2014-September 2019 in patients with FPF, pulmonary fibrosis at young age or personal and/or family extra-pulmonary disease suggestive of STS were analyzed. Results: 150 ILD patients, 73% male, age-at-diagnosis 67 years old, 33% non-smokers, 75% with definite/probable UIP or CPFE, 93% with dyspnea/cough, FVC% pred 75%, DLCO% pred 49% were tested; FPF was 65%, 19% young age, 21% personal and 17% family extra-pulmonary disease suggestive of STS; 21% were tested for more than 1 indication. TRG pathogenic variations were detected in 19 (13%): 13 in a familial, 3 in young age and 3 in extra-pulmonary disease suggestive of STS context as follows: TERT, TERC, RTEL1, PARN, NOP10, NHP2 in 8,5,2,2,1 and 1 respectively. No difference was detected in epidemiological-clinical-radiologic-functional characteristics between patients without and with mutations apart from age-at-diagnosis [69 vs 62 years, p

Introduction: Alpha1-antitrypsin (A1AT) deficiency is an autosomal co-dominant disease related to SERPINA-1 gene mutations predisposing to pulmonary emphysema and/or liver disease. Aim: to examine the genotype and phenotype of a Greek cohort of A1AT-deficiency patients. Methods: This multicenter study enrolled A1AT-deficiency patients under augmentation treatment from 8 centers in Greece. Results: 23 adult patients, 61% male, 17.4% non-smokers, diagnosed at a median age (IQR) of 47(42-58) years with A1AT levels of 0.24 (0.04-0.4) g/L were identified. Indications for A1AT measurement were severe obstructive pulmonary disease at the age Conclusion: In contrast with the literature, where Z and S are the most common A1AT-deficiency alleles, the present study reveals extremely rare deleterious variants in Greek A1AT-deficiency patients under augmentation treatment. Further examination of phenotype-genotype associations and outcome is expected to unveil their clinical significance in the future.

During the lockdown, IPF patients experienced lower than expected COVID-19, suggesting that simple measures for the winter months, such as face masking, clean hands, physical distancing could be adopted as promising advances in non-pharmacological therapyhttps://bit.ly/2ISi2EV

Aim To investigate the perspective of physicians treating chronic airway diseases on the importance of device and substance characteristics influencing the compliance of patients with chronic obstructive airways diseases. Objective We surveyed physicians’ perspective on the impact of device and substance characteristics on patients’ compliance. Methods This study was carried out by running a structured questionnaire, to a total of 144 physicians, conducting personal interviews and evaluating answers on a scale from 1 for most to 6 for least important influencing parameter. Results Overall, the most important parameters influencing patients’ compliance according to physicians’ perspective were rapid onset of action, type of inhalation device and duration of action. Adverse events were considered as the least important parameter. When COPD and asthma were examined separately, the most important parameters influencing compliance were rapid onset of action, ease of use and duration of action. Rapid onset of action was significantly more important in asthma than COPD. Conclusion Onset and duration of action and ease of use were classified higher as important parameters to increase patients’ compliance, according to physicians’ perspective.

We report on a 70-year old woman with dyspnea, systemic lymphadenopathy and abnormal chest computed tomography (CT) findings. A complete laboratory testing as well as mediastinal tissue sampling via Endobronchial Ultrasound (EBUS)-guided Transbronchial Needle Biopsy (TBNB) did not reveal a definite diagnosis. After experiencing acute respiratory failure which led to intensive care unit, the patient underwent a cervical lymph node biopsy which revealed peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). A CT-guided trans-thoracic lung biopsy was performed that showed involvement of the lung parenchyma in the context of PTCL-NOS. Lung involvement is a rare extra-nodal manifestation of PTCL. The imaging patterns of this lymphoma have not been well described. We conclude that the finding of crazy paving pattern is a rare manifestation of this disease. In patients with pre-existing lymphoma, lung involvement should be included in the differential due to high pre-test probability.

Background Nintedanib represents an antifibrotic compound able to slow down disease progression of patients with idiopathic pulmonary fibrosis (IPF). Objective To investigate the safety and efficacy of nintedanib in patients with IPF in a real-life setting. Methods This was a multicentre, retrospective, observational, real-life study for patients with IPF receiving nintedanib between October 2014 and October 2016. Results We identified 94 patients with IPF receiving nintedanib (72 males, mean age±SD: 73.8 ± 7.5, mean%FVC±SD = 68.1 ± 18.3, mean%DLCo±SD = 44.4 ± 14.5). Diarrhea (n = 52, 55.3%) was the most commonly reported adverse event. Twenty patients (21.2%) had to permanently discontinue nintedanib due to severe adverse events. In the 6-months follow-up, median decline in %FVC predicted and %DLCO predicted were 1.36 (95%Cl: 0 to 2.97) and 4.00 (95%Cl: 2.01 to 6.20), respectively, when deaths were censored and excluded from the analysis. At 12 months, mean%FVC±SD and mean%DLCo±SD were 64.5 ± 19.1 and 43.7 ± 15.4, respectively. With regards to mortality, 17 patients (18.1%) died over a study period of 730 days. Conclusion Nintedanib demonstrated an acceptable safety and efficacy profile in our real-world observational study. Prospective observational studies in the context of registries that collect well-defined supporting data over time are sorely needed to answer residual questions on drug's performance.

Background Pirfenidone is a novel anti-fibrotic drug that has shown efficacy in five randomized multicenter clinical trials enrolling patients with Idiopathic Pulmonary Fibrosis of mild-to-moderate disease severity. Scarce data supports the use of pirfenidone in IPF patients with more advanced disease. Objective To investigate the safety and efficacy profile of pirfenidone in IPF patients with severe lung function impairment. Patients and methods This was a retrospective study enrolling patients with advanced IPF (FVC%predicted Results Between September 2011 and March 2013, we identified 43 patients with severe IPF (baseline meanFVC%predicted±SD: 63.8 ± 20.3, meanDL CO %predicted: 27.3 ± 8.2), of mean age±SD: 66.3 + 9.7, 34 males (81%) that received pirfenidone (2.403 mg/daily) for one year. Pirfenidone treatment was associated with a trend towards decrease in functional decline compared to 6-months before treatment initiation but failed to show any benefit after one year of treatment (ΔFVC: −3.3 ± 4.6 vs 0.49 ± 11.4 and vs. −5.8 ± 11.8, p = 0.06 and p = 0.04, respectively and ΔDL CO : −13.3 ± 15.2 vs. −10.1 ± 16.6 and vs. 28.3 ± 19.2, p = 0.39 and p = 0.002, respectively). Gastrointestinal disorders (34.9%), fatigue (23.2%) and photosensitivity (18.6%) were the most common adverse events. Adverse events led to treatment discontinuation in 9 patients (20.9%) and dose reduction in 14 (32.5%). Conclusion Pirfenidone appears to be safe when administered in patients with advanced IPF. Pirfenidone efficacy in IPF patients with severe lung function impairment may diminish after 6 months of treatment.

Introduction: Depression is prevalent in patients with Idiopathic Pulmonary Fibrosis (IPF). The impact of depression on quality of life and its correlation with disease severity in patients with IPF has not been thoroughly evaluated on prospective studies.Patients and Methods: Between 2016 and 2017, we prospectively enrolled 101 patients (80 male, mean age (years) ± SD: 70.8 ± 8.1) with IPF (mean GAP score ± SD: 4.7 ± 1.8) without previous diagnosis of depression. Depressive symptoms were evaluated with Beck's depression inventory-II (BDI-II). Disease severity was evaluated with pulmonary function (FVC, DLCO) and exercise capacity measures. Symptom burden was assessed by cough and dyspnea scales. Health Related Quality of Life (HRQL) was assessed with two questionnaires.Results: Data for analysis was available from 98 patients (97%). Forty two patients (42.9%) presented with depressive symptoms scoring≥14. A significant association between depressive symptoms and measures of: 1) disease severity: a) GAP score: r = 0.32, p = 0.007, b) DLCO: r = −0.28, p = 0.007, c) 6MWD: r = −0.39, p = 0.017, 2) symptom burden: a) cough: r = −0.57, p < 0.001, b) dyspnea (Borg: r = 0.54, p < 0.001, mMRC: r = 0.55, p < 0.001, SOBQ: r = 0.57, p < 0.001 and 3) HRQL: a) SGRQ: (Total score: r = 0.68, p < 0.001, Activity Score: r = 0.60, p < 0.001, Impact score: r = 0.68, p < 0.001, Symptoms score: r = 0.60, p < 0.001, b) K-BILD: r = −0.66, p < 0.001), was identified. There was no statistically significant difference in BDI-II (p = 0.62) and SGRQ (p = 0.64) 1 year after treatment with antifibrotics.Conclusions: Patients with IPF and severe functional impairment tend to have increased risk for depression development and poor quality of life. Further prospective studies should investigate the role of antidepressant drug therapy in patients with IPF and comorbid depression.

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). In a retrospective, real-world study across seven Greek hospitals, we evaluated the effectiveness and safety of nintedanib in routine clinical practice. Patients diagnosed with IPF, as per guideline criteria or multidisciplinary diagnosis, received nintedanib between January 2013 and January 2018. We evaluated 244 patients: mean±sd age 71.8±7.5 years, 79.1% male, 45.1% current smokers and 33.1% ex-smokers at treatment initiation. At baseline, predicted forced vital capacity (FVC) was 73.3±20.7% and predicted diffusing capacity of the lungs for carbon monoxide (DLCO) was 42.6±16.7%. On average, patients spent 23.6±15.0 months on nintedanib. At 3 years, 78 patients had died, equating to a 3-year survival rate of 59.4% (unaffected by treatment discontinuation or dose reduction). FVC% pred and DLCO% pred were largely stable at 3 years, with no significant difference from baseline (FVC 73.3±20.7% pred versus 78±20.1% pred, p=0.074; DLCO 42.6±16.7% pred versus 40.4±18.1% pred, p=0.334). Of the 244 patients, 55.7% reported an adverse event. Gastrointestinal events were the most common (173 (77.2%) out of 224 total events) and 45.0% of patients experienced diarrhoea. Only 32 (13.1%) patients had to permanently discontinue nintedanib due to an adverse event. This real-world study shows a 3-year survival rate of 59.4% and a low discontinuation rate due to adverse events. Our experience is consistent with previous findings in clinical trials of nintedanib in IPF., Findings from the largest registry of Greek patients with IPF receiving nintedanib in routine clinical practice show, over a 3-year period, a low discontinuation rate and efficacy data that support the results of the INPULSIS clinical trials http://bit.ly/35a2CS5

Introduction: Chronic Hypersensitivity Pneumonitis (c-HP) can exhibit an IPF-like course despite immunosuppressive treatment. In this group of patients there is a need for new therapeutic approaches. Aim: To investigate the effect of antifibrotics in the clinical course of c-HP. Patients and Methods: Retrospective analysis of patients with an initial diagnosis of IPF that were subsequently diagnosed as c-HP in the context of multidisciplinary discussion (Jan2012-Dec2016). HP diagnosis was based in the absence of alternative diagnoses when at least two of the following criteria were present: Recognition of an inciting antigen, compatible HRCT pattern (mainly presence of mosaic pattern), BAL lymphocytosis>20%. Results: We enrolled in the study 96 patients with HP. From this cohort we identified 18 patients, initially diagnosed as IPF (16 males, 88,9%, median age 70 years (95% CI for the median 63 to 73.6) that had received antifibrotics for at least 12 months (10 pirfenidone and 8 nintedanib). Mean (±SE) relative changes in %FVCpred and %DLcopred over one year was -4.19±3.29 and -5.72±5.32, respectively. A decline in FVC was observed in 11 patients (in 4 patients > 10%, and in 5 patients between 5-10%). An increase in relative %FVCpred was observed in 7 patients (mean ΔFVC ± SE = 8.69±3.75). Conclusions: Antifibrotics can stabilize FVC decline in patients with c-HP. Large randomized trials are needed.

Background: Abundant evidence supports an association between Idiopathic Pulmonary Fibrosis (IPF) and lung cancer development. Data on diagnosis and management of patients with IPF and lung cancer are still scarce. Aim: To estimate prevalence of lung cancer in patients with IPF. Patients and Methods: This was a retrospective multicenter study, enrolling 835 patients with IPF from eight different centers between 2009 and 2018 in Greece. Results: We identified 88 cases of patients with IPF and lung cancer (prevalence=10.5% n=88/835, mean age±SD=71.8±7.1, 82 males, meanFVC±SD= 73.5±18.9, meanDLCO±SD= 45.3±15.6). Six patients (7%) had both lung and other type of cancer. We identified 68 cases (77.3%) of non-small cell lung cancer (32 squamous, 25 adenocarcinoma, 11 non-specified), and 13 cases (14.8%) of small cell lung cancer. An equal distribution of anatomic location of lung cancer between upper and lower lobes was observed. Lung cancer was diagnosed post IPF diagnosis (median latency time=15.9 months) in 68% of patients and synchronously in 29.3% of patients. Chemotherapy was applied in 31.8% of cases, while 33.3% of patients underwent surgery. Median survival of patients with IPF and lung cancer was 27.4 months (95% CI: 20.6 to 36.8). Conclusions: IPF is a risk factor for lung cancer development. Squamous cell carcinoma is the most common histologic subtype in patients with IPF. Large randomized controlled studies on the management of patients with IPF and lung cancer are sorely needed.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted to humans mainly via contact and droplet transmission and its entry into cells is mediated by the efficient binding of the spike (S) viral protein with the angiotensin converting enzyme-2 (ACE2) receptors. Although acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 fulfills the criteria of the Berlin definition, in a considerable proportion of patients with COVID-19, there is a dissociation between their relatively well-preserved lung mechanics and the severity of hypoxaemia. The extent of pneumococcal related morbidity and mortality is largely unknown. Respiratory comorbidities that increase the risk of severe disease and mortality due to SARS-CoV-2 include chronic obstructive pulmonary disease, asthma, bronchiectasis and fibrotic interstitial lung diseases, regardless of aetiology. Pneumococcal and seasonal influenza vaccinations are useful in preventing a substantial burden of mortality in high-risk populations, while general quarantine and social distancing can reduce the infiltration of the virus within the community. To date, several therapeutic agents have been studied or are currently examined, such as hydroxychloroquine, chloroquine, ritonavir/lopinavir, remdesivir, colchicines and interleukin-6 inhibitors. However, the usage of most of these into clinical practice was not based on randomised clinical trials and their results should be viewed with extreme caution; remdesivir seems to be the more promising option. Rigorous efforts are under way for the development of a safe and successful vaccine against SARS-CoV-2.

Background: Abundant evidence supports an association between Idiopathic Pulmonary Fibrosis (IPF) and lung cancer development. Nevertheless, epidemiological data on IPF and cancer are scarce. Aim: To estimate prevalence of lung and other types of cancer in patients with IPF. Patients and Methods: This was a retrospective multicenter study, enrolling 608 patients with IPF from six different centers between 2009 and 2018. Results: We identified 63 cases of patients with IPF and cancer (prevalence=10.3%, n=63/608, mean age±SD=72.8±7.5, 57 males, meanFVC±SD= 75.9±21.5, meanDLCO±SD= 47.2±15.8). We recorded 50 cases of lung cancer and 16 patients with other types of cancer (colon n=6, stomach n=2, breast n=2, chronic lymphocytic leukemia n=2, other=4). Three patients had both lung and other type of cancer. Prevalence of lung cancer in patients with IPF was 8.2%. Most cases (74%, n=37) were non-small cell lung cancer (20 squamous, 12 adenocarcinoma, 5 non-specified), while in 7 patients (14%) small cell lung cancer was diagnosed. Primary lesion was localized in upper lobes in 52% (n=26) of cases. In 64%(n=32) of patients, lung cancer was diagnosed post IPF diagnosis (median latency time= 14.6 months), 30%(n=15) of patients were diagnosed with IPF and lung cancer synchronously and 6%(n=3) of cases developed lung cancer prior IPF diagnosis(median latency time=23.8 months). Chemotherapy was applied in 36% of cases, while 20% of patients underwent surgery. Median survival of patients with IPF and lung cancer was 24.0 months (95% CI: 18.6 to 38.0). Conclusions: Our epidemiologic data validates IPF as risk factor for cancer development. Further studies are greatly anticipated.

Background Pirfenidone is an antifibrotic compound able to slow down disease progression in patients with idiopathic pulmonary fibrosis (IPF). Objective To investigate the safety and efficacy of pirfenidone in patients with IPF in a real-life setting. Methods This was a multicenter, retrospective, real-life, observational study for patients with IPF receiving pirfenidone. Results We identified 92 patients with IPF receiving pirfenidone. Eighty patients (70 males and 10 females, mean age ± SD: 68.1 + 7.5, mean %FVC ± SD = 74.9 ± 17.2, mean %DLCO ± SD = 48.1 ± 16.9) were included in the analysis. Skin-related (25%) and gastrointestinal (17.5%) adverse events were the most common and led to drug discontinuation in 22.5% of cases. The majority (87%) of patients experienced side effects during the first 6 months of treatment. At 36 months, changes in %FVC and %DLCO were −9.25 ± 16.34 and −9.26 ± 15.26, respectively. At 6, 12, and 24 months after treatment initiation (n = 80, 60, and 26), 18, 15, and 5 patients (22.5, 25, and 19.2%) experienced significant (>10%) and 11, 3, and 3 patients (13.8, 5, and 11.5%) experienced marginal (5–10%) %FVC improvement; and 13, 6, and 1 patient (16.2, 10, and 3.9%) experienced marginal (−5 to −10%) and 20, 21, and 8 patients (25, 35, and 30.8%) experienced significant decline (

The past few years have signaled a major breakthrough on the management of Idiopathic Pulmonary Fibrosis (IPF). Finally, we have drugs in our arsenal able to slow down the inexorable disease natural course. On the other hand, the latter evidence has increased the responsibility for a timely and accurate diagnosis. Establishment of IPF diagnosis, directly affects the choice of appropriate treatment. The current diagnostic guidelines represent a major step forward providing an evidence-based road map; yet, clinicians are encountering major diagnostic dilemmas that inevitably affect therapeutic decisions. This review article aims to summarize the current state of knowledge on the diagnostic procedure of IPF based on the current guidelines and discuss pragmatic difficulties and challenges encountered by clinicians with regards to their applicability in the everyday clinical practice.

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant inherited disease caused by mutations in the folliculin (FLCN) gene. It is characterized by lung cysts, skin fibrofolliculomas and an increased risk for the development of renal cancer, especially chromophobe. Lung cysts in the context of BHDS are typically lower lobe predominant, paramediastinal, in relation to the fissures and often elliptical shaped. Skin manifestations can easily go unnoticed. Respiratory physicians need to have a high degree of vigilance as they can be the first to suspect the disease in the setting of diffuse cystic lung disease. Meticulous skin examination and referral to a dermatologist is of utmost importance as it can establish the diagnosis in the least invasive way. Correct diagnosis is crucial as it may allow for genetic counseling to the affected family and the implementation of a monitoring strategy for early detection of renal cancer.

The introduction of anti-fibrotic agents to clinical practice and the need to better define patient populations for future clinical trials highlight the importance of accurate diagnosis. The main unmet need lies within the population of patients with fibrotic interstitial lung disease (f-ILD) and indeterminate for UIP pattern on HRCT. The differential diagnosis mainly includes idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), interstitial lung disease associated with occult collagen tissue disease and most notably chronic Hypersensitivity Pneumonitis (HP). Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Tzilas has nothing to disclose. Conflict of interest: Dr. TZOUVELEKIS has nothing to disclose. Conflict of interest: Dr. Bouros has nothing to disclose. Conflict of interest: Dr. KARAMPITSAKOS has nothing to disclose. Conflict of interest: Dr. KATSARAS has nothing to disclose. Conflict of interest: Dr. Costabel has nothing to disclose. Conflict of interest: Dr. Wells reports personal fees from Bayer AG, personal fees from Roche, personal fees from Boehringer Ingelheim, during the conduct of the study. Conflict of interest: Dr. BOUROS reports grants, personal fees and non-financial support from BOEHRINGER INGELHEIM, grants, personal fees and non-financial support from ROCHE, grants from ELPEN, outside the submitted work. Conflict of interest: Dr. NTASSIOU has nothing to disclose.

Idiopathic pulmonary fibrosis (IPF) is the most prevalent of the idiopathic interstitial pneumonias (IIPs). It carries an ominous prognosis with a median survival of 3 years. Its epidemiology is poorly described because of its rarity and lack of unanimity in diagnostic and coding practices [1]. However, during the last few years, significant improvement has been achieved in our understanding of the pathogenesis, diagnosis and management of IPF and IIP in general. This is reflected in the 2011 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society/ALAT consensus statement on IPF [2] and the 2013 ATS/ERS update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias [3]. To obtain a robust understanding of the epidemiology of IPF is important, especially as novel therapies are emerging. The International Classification of Disease (ICD) coding system represents a great opportunity to create such registries that will expand our knowledge on IPF epidemiology. However, under its current formation, the 10th edition (ICD-10) coding system has severe deficiencies regarding the accurate classification of IPF. ICD-10 does not adequately classify IPF

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, debilitating disease of unknown etiology that leads to death nearly half of the patients within 3–3.5 years. The past 15 years, the scientific community has made tremendous progress towards standardized diagnostic and prognostic algorithms that led to the generation of the 2011 ATS/ERS/JRS/ALAT guidelines. The latest guidelines provided us with fundamental diagnostic algorithms that set the diagnosis in the majority of cases; however, they leave a significant minority of patients without diagnostic and most importantly, therapeutic umbrella. To this end current guidelines should be revisited in light of research advances, including the tools of “fibromics” and at the same time provide practical guidance to the real-world of IPF in order to address patients' needs. The scope of this review article is to summarize challenges in the everyday IPF clinical practice and make an effort to provide realistic answers to patients' questions.

Idiopathic pulmonary fibrosis, 1 of the 7 idiopathic interstitial pneumonias, carries an ominous prognosis. It has a median survival of 2.8 years. However, there is significant heterogeneity in the actual length of survival, which varies from months to >5 years. Unfortunately, in addition to lung transplantation, no known medical intervention alters the natural history of the disease. Currently, many phase-III clinical trials are ongoing, but there is no Federal Drug Administration approved therapy. Thus, it is important for the clinician to be able to evaluate prognostic factors. These will help him draw conclusions about the possible course of his idiopathic pulmonary fibrosis patients and make important therapeutic decisions (lung transplantation).