Expression of PD-1/PD-L1 axis in mediastinal lymph nodes and lung tissue of human and experimental lung fibrosis indicates a potential therapeutic target for idiopathic pulmonary fibrosis.

BACKGROUND: Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking. METHODS: Programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1) expression in mediastinal lymph nodes and lung tissues was analyzed. PD-1, PD-L1 mRNA expression was measured in tracheobronchial lymph nodes of mice following bleomycin-induced injury on day 14. Finally, the effect of the PD-1 inhibitor, pembrolizumab, in bleomycin-induced pulmonary fibrosis was investigated. RESULTS: We analyzed mediastinal lymph nodes of thirty-three patients (n = 33, IPF: n = 14, lung cancer: n = 10, concomitant IPF and lung cancer: n = 9) and lung tissues of two hundred nineteen patients (n = 219, IPF: 123, controls: 96). PD-1 expression was increased, while PD-L1 expression was decreased, in mediastinal lymph nodes of patients with IPF compared to lung cancer and in IPF lungs compared to control lungs. Tracheobronchial lymph nodes isolated on day 14 from bleomycin-treated mice exhibited increased size and higher PD-1, PD-L1 mRNA levels compared to saline-treated animals. Pembrolizumab blunted bleomycin-induced lung fibrosis, as indicated by reduction in Ashcroft score and improvement in respiratory mechanics. CONCLUSIONS: Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles than those of patients with lung cancer indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis. PD-1 expression in mediastinal lymph nodes is in line with lung tissue expression. Lower doses of pembrolizumab might exert antifibrotic effects. Clinical trials aiming to endotype patients based on mediastinal lymph node profiling and accordingly implement targeted therapies such as PD-1 inhibitors are greatly anticipated.

Safety and Effectiveness of Mycophenolate Mofetil in Interstitial Lung Diseases: Insights from a Machine Learning Radiographic Model.

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.

Tocilizumab improves 28-day survival in hospitalized patients with severe COVID-19: an open label, prospective study.

BACKGROUND: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched. METHODS: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10. FINDINGS: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21-9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0-24.0), HR: 1.32 (95% CI: 0.84-2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0-84.7) vs 15.8 (95% CI: - 19.4-50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005). CONCLUSION: Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.

Increased monocyte count and red cell distribution width as prognostic biomarkers in patients with Idiopathic Pulmonary Fibrosis.

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 < 0.60 K/µL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2-79.2) vs. 78.3, (95% CI 76.0-81.0), (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 < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5-41.1) vs. 45.5, (95% CI 41.9-49.4), (P < 0.001)] and RDW [37.9, (95% CI 33.4-40.7) vs. 44.4, (95% CI 41.5-48.9), (P < 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (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 (< 0.60 K/µL) [HR 2.05, (95% CI 1.19-3.53), (P = 0.01)]. CONCLUSIONS: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Blood eosinophils as predictor of outcomes in patients hospitalized for COPD exacerbations: a prospective observational study.

PURPOSE: In the present prospective multicentre observational study, we evaluated the potential role of blood eosinophils on the outcomes of patients hospitalized for COPD exacerbations. MATERIAL AND METHODS: Consecutive patients >40 years with a previous COPD diagnosis were recruited. Blood eosinophils were measured on admission prior to the initiation of treatment and were evaluated in three groups (<50, 50-149 and ≥150 cells/µL). Patients received standard care and were followed up for a year. RESULTS: A total of 388 patients were included (83.5% male, mean age 72 years). Patients with higher blood eosinophils had less dyspnoea (Borg scale), lower C-reactive protein (CRP) and higher PaO2/FiO2 (partial pressure for oxygen/fraction of inhaled oxygen), and were discharged earlier (median 11 vs. 9 vs. 5 days for patients with <50, 50-149 and ≥150 cells/µL, respectively). Patients with <50 cells/µL presented higher 30-day and 1-year mortality, whereas there were no differences in moderate/severe COPD exacerbations between the three groups. In a post hoc analysis, treatment with inhaled corticosteroids as per physicians' decision was associated with better exacerbation prevention during follow-up in patients with ≥150 cells/µL. CONCLUSIONS: Higher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker.

Thoracic endosonography (EBUS/EUS-b) in the diagnosis of different intrathoracic diseases: A 4-year experience at a single-centre in Greece.

BACKGROUND: In the last decade, the advent of thoracic endosonography has revolutionised the field of diagnostic bronchoscopy. METHODS: We conducted a single-centre prospective study in "Sotiria" Chest diseases hospital between January 2016 and December 2019. The study aimed to evaluate the efficacy and diagnostic value of combined EBUS/EUS-b in comparison with EBUS-TBNA and EUS-b FNA in different intrathoracic diseases. RESULTS: A total of 266 patients were enrolled (70.7% males, 85.7% smokers, mean age ± SD: 62.8 ± 11.8). Diagnosis and staging of suspected lung cancer (LC) were the main indications for EBUS/EUS-b in 56.7% of patients, followed by lymphadenopathy of unknown origin in 27%, lymphadenopathy in previous malignancy in 10.9%, and staging of proven LC in 5.3%. EUS-b FNA alone or combined with EBUS-TBNA was performed in 14.7% of patients. A total of 512 lymph nodes was sampled (481 through EBUS-TBNA and 31 through EUS-b FNA). EBUS/EUS-b led to a definitive diagnosis in 68.4% of the patients. Most cases (50.4%) were malignancies, while 18% represented benign diseases (83.3% sarcoidosis). Sensitivity of combined EBUS/EUS-b was higher in comparison with sensitivity of both procedures alone (100% vs 89.4% vs 88.9%). Accordingly, the overall sensitivity of EBUS/EUS-b for the detection of malignancy and sarcoidosis was 93% and 95.2%, respectively. No severe complications were observed. CONCLUSION: Thoracic endosonography is an efficient, safe, minimally invasive tool yielding high sensitivity and diagnostic accuracy in patients with suspected malignancy and mediastinal lymphadenopathy. Experienced pulmonologists in EBUS-TBNA should more routinely perform EUS-b FNA to avoid unnecessary surgical interventions.

Platypnea orthodeoxia syndrome in a patient with patent foramen ovale and normal atrial pressure. Case report and presentation of underlying pathophysiological mechanisms.

Platypnea-orthodeoxia Syndrome is characterized by clinically significant postural hypoxia. The full spectrum of the syndrome includes intracardial and extracardial abnormalities with R->L shunt. Various concurrent underlying physiological abnormalities are usually encountered that require thorough clinical and laboratory evaluation. A high clinical suspicion in patients with unexplained dyspnea is also required to reach a firm diagnosis. We herein present a rare case of an 82-years-old patient with episodic unexplained dyspnea, patent foramen ovale with normal pulmonary pressures and we review the underlying physiologic mechanisms.

Low penetrance of antibiotics in the epithelial lining fluid. The role of inhaled antibiotics in patients with bronchiectasis.

Plasma drug concentrations, spectrum of antibacterial activity and minimum inhibitory concentration (MIC) had been widely considered as markers of the efficacy of antibiotics. Nonetheless, in several cases, antibiotics characterized by all these features were ineffective for the treatment of respiratory tract infections. A typical paradigm represented the case of patients with bronchiectasis who do not always benefit from antibiotics and thus experiencing increased sputum production, worse quality of life, more rapid forced expiratory volume in the first second (FEV1) decline, more frequent exacerbations and increased mortality rates, especially those with Pseudomonas aeruginosa (P. aeruginosa) chronic infection. Subsequently, penetrance of antibiotics in the epithelial lining fluid has gradually emerged as another key factor for the outcome of antibiotic treatment. Given that a plethora of antibiotics presented with poor or intermediate penetrance in the epithelial lining fluid, inhaled antibiotics targeting directly the site of infection emerged as a new option for patients with respiratory disorders including patients with bronchiectasis. This review article intends to summarize the current state of knowledge for the penetrance of antibiotics in the epithelial lining fluid and present results from clinical trials of inhaled antibiotics in patients with bronchiectasis of etiology other than cystic fibrosis.

The role of increased red cell distribution width as a negative prognostic marker in patients with COPD.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) remains a major burden with no clinically applicable biomarkers. AIM: To investigate the association of Red cell Distribution Width (RDW) values on admission with previous hospitalizations, need of non-invasive mechanical ventilation (NIMV) and long term oxygen therapy (LTOT) in patients with COPD. METHODS: Patients with AECOPD admitted to our department during 2018 were included in the study. RESULTS: One hundred sixty patients were enrolled (M/F 95/65, median age 71.00 years, mean FEV1± SD = 46.6 ± 28.9). Median RDW was significantly higher for patients in need of NIMV (14.8, 95% CI: 14.2 to 15.6) than patients not in need of NIMV (13.5, 95% CI: 13.2 to 13.8) (p < 0.001). Median RDW was significantly higher for patients in need of LTOT (14.2, 95% CI: 13.7 to 14.6) compared to patients not receiving LTOT (13.2, 95% CI: 12.5 to 13.6) (p = 0.001). Patients with hospitalization during the last 12 months had increased RDW values compared to patients with no hospitalizations [median RDW 14.3, (95% CI: 13.5 to 14.9) versus median RDW 13.5, (95% CI: 13.1 to 13.9)](p = 0.001). CONCLUSION: Patients with COPD in need of LTOT, NIMV or patients with previous hospitalizations presented with increased RDW values. Increased RDW values could serve as a negative prognostic marker in patients with COPD.

Coexistence of Autoimmune Pulmonary Alveolar Proteinosis With Small Cell Lung Cancer in a Man Presenting With Acute Onset Respiratory Failure.

A 60-year-old man was referred to our Respiratory Department with progressive dyspnea on exertion and productive cough over the past two months. High-resolution computed tomography showed diffuse ground glass opacities with superimposed interlobular and intralobular septal thickening mainly in the middle and lower lobes, compatible with crazy paving pattern. Serology tests revealed positive antibody transcriptional intermediary factor-γ1 (TIF-1γ) in myositis panel and bronchoalveolar lavage revealed milky appearance and positive periodic acid-Schiff (PAS) stain. Pulmonary function tests showed moderate reduction in diffusing capacity for carbon monoxide. The working diagnosis of autoimmune pulmonary alveolar proteinosis was established by high detectable levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. Despite clinical and radiological improvement following treatment with whole lung lavage and inhaled sargramostim, patient's follow-up chest computed tomography revealed an enlargement of lower left paratracheal lymph node 4L. Endobronchial ultrasound bronchoscopy (EBUS) biopsy was compatible with small cell lung cancer (SCLC). Chemotherapeutic agents were promptly administrated, with no adverse events up until now.

Eosinopenia as a Prognostic Biomarker for Noninvasive Ventilation Use in COPD Exacerbations.

BACKGROUND: In recent years, blood eosinophils have been evaluated as a surrogate biomarker for eosinophilic airway inflammation and as a prognostic indicator of the outcomes of hospitalized COPD subjects. During an exacerbation of COPD, eosinopenia has been proposed as a prognostic marker of adverse outcomes. OBJECTIVES: The aim of the present post hoc analysis was to elucidate the effectiveness of blood eosinophils for predicting the need of NIV in subjects with COPD exacerbation. METHODS: Consecutive subjects admitted to a hospital for COPD exacerbation were included in the analysis. The eosinophil count from the first complete blood count was used to designate the eosinophil groups. The relationship between the clinical characteristics and blood eosinophil counts, as dichotomized using 150 cells/µL, was evaluated. Results Subjects with blood eosinophil number < 150 k/µL had a more severe disease on admission compared to subjects with ≥150 k/µL, regarding pH 7.400 (7.36, 7.44) vs. 7.42 (7.38, 7.45), p = 0.008, PO2/FiO2 levels 238.1 (189.8, 278.6) vs. 276.2 (238.2, 305.6), p < 0.001, CRP (mg/L) levels 7.3 (3.1, 19.9) vs. 3.5 (0.7, 7.8), p < 0.001 and required a longer hospital stay (days) 10.0 (8.0, 14.0) vs. 5.0 (3.0, 7.0) p < 0.001 respectively. The number of blood eosinophils correlated with the levels of CRP upon admission (p < 0.001, r = -0.334), with arterial pH upon admission (p < 0.030, r = 0.121), with PO2/FiO2 (p < 0.001, r = -0.248), and with duration of hospital stay (p < 0.001, r = -0.589). In the multinomial logistic regression analysis, blood eosinophil count < 150 k/µL was an independent predictor of the use of NIV during hospital stay. CONCLUSION: During COPD exacerbation, low blood eosinophil levels upon admission are related to more severe disease and can be used as a predictor of the need of NIV. Further prospective studies are needed to identify the use of blood eosinophil levels as a predictor of unfavorable outcomes.

Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial.

OBJECTIVE: Randomized controlled trials comparing tocilizumab and baricitinib in patients with coronavirus disease 2019 (COVID-19) are needed. This was an open-label, randomized controlled trial aiming to address this unmet need. METHODS: To determine whether baricitinib was non-inferior to tocilizumab, we assessed whether the upper boundary of the two-sided 95% CI of the hazard ratio (HR) did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10. RESULTS: We assigned 251 patients with COVID-19 and a PaO2/FiO2 ratio of <200 to receive either tocilizumab (n = 126) or baricitinib (n = 125) plus standard of care. Baricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (mechanical ventilation or death for patients who received baricitinib, 39.2% [n = 49/125]; mechanical ventilation or death for patients who received tocilizumab, 44.4% [n = 56/126]; HR, 0.83; 95% CI, 0.56-1.21; p 0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (patients who received baricitinib- discharged alive: 58.4% [n = 73/125] vs. patients who received tocilizumab- discharged alive: 52.4% [n = 66/126]; HR, 0.85; 95% CI, 0.61-1.18; p < 0.001 for non-inferiority). There was no significant difference between the baricitinib and tocilizumab arms in the change in WHO scale at day 10 (0.0 [95% CI, 0.0-0.0] vs. 0.0 [95% CI, 0.0-1.0]; p 0.83). DISCUSSION: In the setting of this trial, baricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19.

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

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

Fanconi syndrome-associated interstitial lung disease.

A middle-aged man was referred to our respiratory department with dyspnoea progressively deteriorating and non-productive cough over the past 8 months. High-resolution CT revealed multiple bilateral consolidations, traction bronchiectasis, reticular pattern and honeycombing with basal and peripheral predominance. Serology tests were negative. Pulmonary function tests showed moderate restrictive functional impairment and severe reduction in diffusing capacity for carbon monoxide. Meticulous evaluation of patient's medical history revealed recent administration of oral corticosteroid due to pulmonary fibrosis potentially in the context of Fanconi syndrome diagnosed at childhood. The working diagnosis of interstitial lung disease (ILD) as a rare complication of Fanconi syndrome was proposed following multidisciplinary discussion. Despite combination treatment with low doses of corticosteroids and antifibrotic compound, the patient exhibited clinical, radiological and functional deterioration, was admitted to intensive care unit due to respiratory failure following infection-driven progression of fibrotic ILD and finally died.

High-Flow vs. Low-Flow Nasal Cannula in Reducing Hypoxemic Events During Bronchoscopic Procedures: A Systematic Review and Meta-Analysis.

Introduction: High-flow nasal cannula (HFNC) oxygenation method has been proven to be successful in oxygenation of patients with respiratory failure and has exhibited clinical superiority compared to low-flow nasal cannula (LFNC). Methods: We performed a systematic review and meta-analysis to evaluate the potential favorable impact of HFNC oxygenation during bronchoscopy and related procedures like endobronchial ultrasound-transbronchial needle aspiration. Only randomized control trials (RCTs) were included in the meta-analysis. Results: Six randomized control trials with 1,170 patients were included in this meta-analysis. Patients who underwent bronchoscopy with the use of high-flow nasal cannula experienced less hypoxemic events/desaturations, less procedural interruptions and pneumothoraxes compared to patients under low-flow nasal cannula treatment. This beneficial effect of HFNC in hypoxemic events was persistent 10 min after the end of procedure. Conclusion: The high-flow nasal cannula (HFNC) oxygenation method could reduce hypoxemic events and related peri- and post-bronchoscopic complications.

Diagnostic Accuracy of Multiple D-Dimer Cutoff Thresholds and Other Clinically Applicable Biomarkers for the Detection and Radiographic Evaluation of Pulmonary Embolism.

Background: Diagnostic work-up of pulmonary embolism (PE) remains a challenge. Methods: We retrospectively studied all patients referred for computed tomography pulmonary angiography (CTPA) with suspicion of PE during a 12-month period (2018). The diagnostic accuracy of different D-dimer (Dd) cutoff thresholds for ruling out PE was evaluated. Furthermore, the association of Dd and red cell distribution width (RDW) with embolus location, CTPA findings, and patient outcome was recorded. Results: One thousand seventeen (n = 1017) patients were finally analyzed (mean age: 64.6 years (SD = 11.8), males: 549 (54%)). PE incidence was 18.7%. Central and bilateral embolism was present in 44.7% and 59.5%, respectively. Sensitivity and specificity for conventional and age-adjusted Dd cutoff was 98.2%, 7.9%, and 98.2%, 13.1%, respectively. A cutoff threshold (2.1 mg/L) with the best (64.4%) specificity was identified based on Receiver Operating Characteristics analysis. Moreover, a novel proposed Dd cutoff (0.74 mg/L) emerged with increased specificity (20.5%) and equal sensitivity (97%) compared to 0.5 mg/L, characterized by concurrent reduction (17.2%) in the number of performed CTPAs. Consolidation/atelectasis and unilateral pleural effusion were significantly associated with PE (p < 0.05, respectively). Patients with consolidation/atelectasis or intrapulmonary nodule(s)/mass on CTPA exhibited significantly greater median Dd values compared to patients without the aforementioned findings (2.34, (IQR 1.29−4.22) vs. 1.59, (IQR 0.81−2.96), and 2.39, (IQR 1.45−4.45) vs. 1.66, (IQR 0.84−3.12), p < 0.001, respectively). RDW was significantly greater in patients who died during hospitalization (p = 0.012). Conclusions: Age-adjusted Dd increased diagnostic accuracy of Dd testing without significantly decreasing the need for imaging. The proposed Dd value (0.74 mg/L) showed promise towards reducing considerably the need of CTPA. Multiple radiographic findings have been associated with increased Dd values in our study.

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.

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.

Clinical features and outcomes of patients with myositis associated-interstitial lung disease.

Introduction: Myositis associated interstitial lung disease (ILD) seems to be an under-recognized entity. Methods: In this multicenter, retrospective study, we recorded between 9/12/2019 and 30/9/2021 consecutive patients who presented in five different ILD centers from two European countries (Greece, France) and received a multidisciplinary diagnosis of myositis associated-ILD. The primary outcome was all-cause mortality over 1 year in specific subgroups of patients. Secondary outcomes included comparison of disease characteristics between patients diagnosed with the amyopathic subtype and patients with evidence of myopathy at diagnosis. Results: We identified 75 patients with myositis associated-ILD. Median age (95% CI) at the time of diagnosis was 64.0 (61.0-65.0) years. Antinuclear antibody testing was positive in 40% of the cohort (n = 30/75). Myopathy onset occurred first in 40.0% of cases (n = 30), ILD without evidence of myopathy occurred in 29 patients (38.7%), while 16 patients (21.3%) were diagnosed concomitantly with ILD and myopathy. The commonest radiographic pattern was cellular non-specific interstitial pneumonia (NSIP) and was observed in 29 patients (38.7%). The radiographic pattern of organizing pneumonia was significantly more common in patients diagnosed with the amyopathic subtype compared to patients that presented with myopathy [24.1% (n = 7/29) vs. 6.5% (n = 3/46), p = 0.03]. One year survival was 86.7% in the overall population. Kaplan-Meier analysis demonstrated significantly higher all-cause 1-year mortality in patients with the amyopathic subtype compared to patients with evidence of myopathy [H R 4.24 (95% CI: 1.16-15.54), p = 0.03]. Patients diagnosed following hospitalization due to acute respiratory failure experienced increased risk of 1-year all-cause mortality compared to patients diagnosed in outpatient setting [HR 6.70 (95% CI: 1.19-37.81), p = 0.03]. Finally, patients with positive anti-MDA5 presented with higher 1-year all-cause mortality compared to anti-MDA5 negative patients [HR 28.37 (95% CI: 5.13-157.01), p = 0.0001]. Conclusion: Specific ILD radiographic patterns such as NSIP and organizing pneumonia may herald underlying inflammatory myopathies. Hospitalized patients presenting with bilateral organizing pneumonia refractory to antibiotics should be meticulously evaluated for myositis associated-ILD even if there is no overt muscular involvement. Incorporation of ILD radiological patterns in the diagnostic criteria of inflammatory myopathies may lead to timely therapeutic interventions and positively impact patients' survival.

Infliximab-induced interstitial lung disease.

A 70-year-old man was referred to our respiratory department with non-productive cough over the past 6 months. High-resolution CT revealed reticular pattern with basal and peripheral predominance, centrilobular nodules and mild ground glass opacities. Serology tests were normal and bronchoalveolar lavage revealed lymphocytosis. Pulmonary function tests showed functional impairment and reduced diffusing capacity for carbon monoxide. Meticulous evaluation of patient's medical history unveiled longitudinal administration of infliximab due to diagnosis of psoriasis. The working diagnosis of drug-induced interstitial lung disease was proposed following multidisciplinary discussion. Considerable radiological and functional improvement was determined 6 months following infliximab discontinuation without implementation of corticosteroids. To this end, the patient has reported remission of cough and functional improvement.