Establishing a Multidisciplinary Team-Based Pleural Service in the Era of Financial Austerity: The Role of the Thoracic Surgeon.

Medical thoracoscopy/pleuroscopy has become, after bronchoscopy, the second most commonly utilized endoscopic procedure in interventional pulmonology. Due to their common origin, medical thoracoscopy/pleuroscopy and video-assisted thoracic surgery (VATS) are quite similar procedures technically. In contrast to the prevailing attitude that it should predominantly be performed by interventional pulmonologists, we believe that, like all hybrid-in-nature techniques, it should be implemented as part of a combined specialist care service/team. Herewith, we describe our attempt to establish a multidisciplinary pleural disease program during a difficult economic period for our country, comprising thoracic surgeons, pulmonologists and anesthesiologists, all of whom brought in their experience, expertise and resources to establish and develop the service resulting in a hybridization of the technique, with, as reported, quite favorable results.

Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study.

BACKGROUND: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability. PATIENTS AND METHODS: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. RESULTS: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. CONCLUSION: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse," complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized" medical care driven by genotypes in the near future.

Long-term personal air pollution exposure and risk for acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Urban air pollution is involved in the progress of idiopathic pulmonary fibrosis (IPF). Its potential role on the devastating event of Acute Exacerbation of IPF (AE-IPF) needs to be clarified. This study examined the association between long-term personal air pollution exposure and AE- IPF risk taking into consideration inflammatory mediators and telomere length (TL). METHODS: All consecutive IPF-patients referred to our Hospital from October 2013-June 2019 were included. AE-IPF events were recorded and inflammatory mediators and TL measured. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O3, NO2, PM2.5 [and PM10, based on geo-coded residential addresses. Logistic regression models assessed the association of air pollutants' levels with AE-IPF and inflammatory mediators adjusting for potential confounders. RESULTS: 118 IPF patients (mean age 72 ± 8.3 years) were analyzed. We detected positive significant associations between AE-IPF and a 10 µg/m3 increase in previous-year mean level of NO2 (OR = 1.52, 95%CI:1.15-2.0, p = 0.003), PM2.5 (OR = 2.21, 95%CI:1.16-4.20, p = 0.016) and PM10 (OR = 2.18, 95%CI:1.15-4.15, p = 0.017) independent of age, gender, smoking, lung function and antifibrotic treatment. Introduction of TL in all models of a subgroup of 36 patients did not change the direction of the observed associations. Finally, O3 was positively associated with %change of IL-4 (p = 0.014) whilst PM2.5, PM10 and NO2 were inversely associated with %changes of IL-4 (p = 0.003, p = 0.003, p = 0.032) and osteopontin (p = 0.013, p = 0.013, p = 0.085) respectively. CONCLUSIONS: Long-term personal exposure to increased concentrations of air pollutants is an independent risk factor of AE-IPF. Inflammatory mediators implicated in lung repair mechanisms are involved.

Lung cancer in patients with Idiopathic Pulmonary Fibrosis. A retrospective multicenter study in Greece.

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. PATIENTS AND METHODS: This was a retrospective multicenter study, enrolling 1016 patients with IPF from eight different centers between 2011 and 2018 in Greece. Our aim was to estimate prevalence of lung cancer in patients with IPF in Greece. RESULTS: We identified 102 cases of patients with IPF and lung cancer (prevalence = 10.03% n = 102/1016, mean age±SD = 71.8 ± 6.9, 96 males, mean FVC±SD = 72.7 ± 19.7, mean DLCO±SD = 44.5 ± 16.3). We identified 85 cases (83.3%) of non-small cell lung cancer (35 squamous, 28 adenocarcinoma), and 15 cases (14.7%) of small cell lung cancer. Primary lesion was localized in lower lobes in 57.1% of cases. Lung cancer was diagnosed post IPF diagnosis (mean latency time + SD = 33.2 + 36.1 months) in 57.6% of patients and synchronously in 36.5% of patients. Chemotherapy was applied in 26.7% of cases, while 34.7% 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. In line with current literature, 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.

High levels of IL-6 and IL-8 characterize early-on idiopathic pulmonary fibrosis acute exacerbations.

INTRODUCTION: Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients. METHODS: Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-ß) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied. RESULTS: Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines. CONCLUSION: High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-ß, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.

Ability of using different dry powder inhalers during COPD exacerbations.

BACKGROUND: Guidelines suggest that patients hospitalized for acute COPD exacerbations (AECOPD) are treated with short acting bronchodilators. Long acting bronchodilators, offer longer symptom relief but since they are usually administered via Dry Powder Inhalers (DPIs) it is considered that during AECOPD patients would not be able to achieve appropriate inspiratory flow (IF) to receive appropriate drug doses. The aim of the present study was to evaluate whether patients admitted to the hospital for AECOPD, are able to achieve the necessary IF using different DPIs. METHODS: IF was measured daily in patients admitted for AECOPD with a portable IF meter (In-Check Oral inhaler assessment kit), containing a series of adapters that simulate the resistance of 4 DPIs [Turbuhaler (T), Breezhaler/Aerolizer (B/F), Discus (A/A/D) and Handinhaler (HH)]. Dyspnea, spirometry and arterial blood gases were also recorded daily. RESULTS: 44 consecutive patients were included in the study. The majority of patients were able to achieve an IF over 30 L/min with all four device resistances. This minimum required IF was achieved in 90.9%, 100%, 95.5% and 81.8% of patients on admission and in 100%, 100%, 97.7%, and 95.5% of patients on discharge for T, B/F, A/A/D and HH respectively. No functional characteristic was able to predict the achievement of this minimum necessary IF. CONCLUSION: Most patients hospitalized for AECOPD, are able to receive treatment with long acting bronchodilators administered via DPIs. The possible beneficial effects of such an intervention should be tested in further studies.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) and non small cell lung cancer: case presentation and review of the literature.

Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier's disease, is a systemic non inflammatory disease of unknown cause. It is characterized by the presence of osteophytes due to calcification and ossification of spinal ligaments and entheses. Moreover, diffuse idiopathic skeletal hyperostosis has been associated with a variety of metabolic disorders. However, to the best of our knowledge no association with non small cell lung cancer (NSCLC) has been reported so far. In the present study we report a case of a patient with NSCLC and DISH.

"Luck's always to blame": silent wounds of a penetrating gunshot trauma sustained 20 years ago.

Gunshot tracheal injuries represent life-threatening events and usually necessitate emergent surgical intervention. We report a case of an exceptional finding of a patient with retained ballistic fragments in the soft tissues of the thorax, proximal to the right subclavian artery and the trachea, carrying silently his wounds for two decades without any medical or surgical intervention. The bullet pellet on the upper part of the trachea seen accidentally in the chest computed tomography, was also found during bronchoscopy. In short "luck's always to blame".

Molecular and Genetic Biomarkers in Idiopathic Pulmonary Fibrosis: Where Are We Now?

Idiopathic pulmonary fibrosis (IPF) represents a chronic progressive fibrotic interstitial lung disease of unknown cause with an ominous prognosis. It remains an unprecedent clinical challenge due to its delayed diagnosis and unpredictable clinical course. The need for accurate diagnostic, prognostic and predisposition biomarkers in everyday clinical practice becomes more necessary than ever to ensure prompt diagnoses and early treatment. The identification of such blood biomarkers may also unravel novel drug targets against IPF development and progression. So far, the role of diverse blood biomarkers, implicated in various pathogenetic pathways, such as in fibrogenesis (S100A4), extracellular matrix remodelling (YKL-40, MMP-7, ICAM-1, LOXL2, periostin), chemotaxis (CCL-18, IL-8), epithelial cell injury (KL-6, SP-A, SP-D), autophagy and unfolded protein response has been investigated in IPF with various results. Moreover, the recent progress in genetics in IPF allows for a better understanding of the underlying disease mechanisms. So far, the causative mutations in pulmonary fibrosis include mutations in telomere-related genes and in surfactant-related genes, markers that could act as predisposition biomarkers in IPF. The aim of this review is to provide a comprehensive overview from the bench to bedside of current knowledge and recent insights on biomarkers in IPF, and to suggest future directions for research. Large-scale studies are still needed to confirm the exact role of these biomarkers.

Effects of short-term air pollution exposure on symptoms development in the course of idiopathic pulmonary fibrosis.

BACKGROUND: Lately a potential detrimental effect of air pollution to idiopathic pulmonary fibrosis emerged. We aimed to assess the effects of short-term air pollution exposure to the clinical course of IPF. RESEARCH DESIGN AND METHODS: IPF patients were followed intensively for four nonconsecutive study periods between 13 July 2020 and 5 September 2021. Short-term exposure to O3, NO2 and PM10 concentrations was estimated using spatio-temporal land use regression models. Associations among symptoms, lung function, oxygen saturation, and short-term personal air pollutant exposure were assessed through multiple mixed effects logistic regression models. RESULTS: Data for up to 24 IPF patients (mean age: 72.2 ± 7.6 years) were analyzed. We detected positive significant associations between cough and a 10 µg/m3 increase in same day mean level of NO2 (OR = 1.59, 95%CI: 1.00-2.53), PM10 (OR = 2.42, 95%CI: 1.54-3.79), and O3 (OR = 1.63, 95%CI: 1.14-2.32). A 10 µg/m3 increase in same day mean level of NO2 was also associated with the risk of appearance of wheezing (OR = 3.01, 95%CI: 1.00-9.04), while exposure to O3 was associated with common cold (OR = 6.30, 95%CI: 3.59-11.07). No significant associations were detected between short-term exposure to air pollutants and forced vital capacity or saturation of oxygen. CONCLUSIONS: Short-term exposure to increased concentrations of air pollutants is an independent risk factor for IPF symptoms' aggravation.

The Impact of COVID-19 Pandemic on Surgical Treatment of Resectable Non-Small Cell Lung Cancer in Greece.

Background: The coronavirus disease (COVID-19) pandemic has posed an unprecedented challenge to health systems, and has significantly affected the healthcare of lung cancer patients. The aim of our study was to assess the impact of COVID-19 on early lung cancer patients' surgical treatment. Methods: All consecutive patients with early-stage non-small cell lung cancer eligible for surgical treatment stage I/II and resectable stage III, referred to our department during the first wave of COVID-19 between February to May 2020, were included and compared with those on the exact corresponding quarter in 2019, one year before the pandemic. Waiting time to surgical treatment, increase of tumor's size and increase on lung cancer stage were recorded and compared. All subjects were followed up for 12 months. Multiple linear and logistic regression models were applied to assess the differences in the management of the studied groups adjusting for potential confounders. Results: Sixty-one patients with early-stage lung cancer were included in the study; 28 (median age 67 years, SD: 7.1) during the pandemic and 33 (median age 67.1 years, SD: 7.5) one year earlier. A significantly longer period of waiting for treatment and an increase in tumor size were observed during the pandemic compared to before the pandemic [median time 47 days, interquartile rate (IQR): 23−100] vs. [median time 18 days, IQR: 11−23], p < 0.001. No significant differences were detected in the increase of the stage of lung cancer between the subgroups. Conclusion: The COVID-19 pandemic had a significant impact on surgical and oncological care, leading to significant delays on treatment and an increase in tumor size in early-stage lung cancer patients.

Association of Broad-Spectrum Antibiotic Therapy and Vitamin E Supplementation with Vitamin K Deficiency-Induced Coagulopathy: A Case Report and Narrative Review of the Literature.

Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.

Corrigendum: Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.

[This corrects the article DOI: 10.3389/fmed.2022.1083264.].

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

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

Reduced immunogenicity of the mRNA vaccine BNT162b2 in patients with idiopathic pulmonary fibrosis.

Patients with #IPF do not mount appreciable anti-spike antibody responses to two doses of #SARSCoV2 mRNA vaccine compared to the general population. National authorities should prioritise patients with IPF for booster doses. https://bit.ly/3K2KXQ0.

Pulmonary hemorrhage in patients receiving anti-platelets- a case series and a suggested therapeutic algorithm.

Antiplatelet therapy including aspirin and thienopyridine agents (such as clopidogrel, prasugrel and ticagrelor) are often used in patients with coronary disease. Pulmonary hemorrhage due to antiplatelet therapy although very rare, when excessive, is a life-threatening event. So far, there is lack of specific guidelines for the management of these patients. We report a case series of 5 patients receiving antiplatelet therapy who were admitted to the hospital due to pulmonary hemorrhage related to antiplatelet therapy. We also propose an algorithm on the management of these patients taking into consideration the balance between thrombotic and bleeding risk and the severity of the hemorrhage.

Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.

Introduction: Post-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD). Methods: In this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1. Results: Two hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and <60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and <60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and <5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5-29% and <5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic. Conclusion: Post-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are "immature." Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches.