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We present the first reported case of

Background Prior studies demonstrate that donor-derived cell-free DNA (dd-cfDNA) in lung transplant recipients may serve as a marker of allograft injury for detecting allograft rejection and infection. Clinical interpretation of dd-cfDNA requires understanding its biological variation in stable lung transplant patients in order to identify abnormal results suggesting underlying allograft dysfunction. This study establishes the biological variation and reference change values (RCV) of dd-cfDNA in stable lung transplant recipients using an analytically validated assay with an established analytic coefficient of variation (CVA). Methods The AlloSure® assay, a targeted, sequencing-based approach, was used to measure plasma dd-cfDNA in a cohort of lung transplant patients at 4 centers that used dd-cfDNA to monitor for allograft dysfunction in preference to surveillance transbronchial biopsy. Patients with stable allograft function and ≥3 dd-cfDNA samples were included. Intraindividual coefficient of variation (CVI), interindividual CV (CVG), index of individuality (II) and the RCV were calculated. Results Thirty-five patients with a combined 124 dd-cfDNA samples were included in the final analysis. The median dd-cfDNA was 0.31% (interquartile range 0.18%-0.68%), the 97.5th percentile and 95th percentile were 1.3% and 1.0%, respectively. In 30 stable patients with an average of 3.7 tests, the CVI was 25%, CVG 53%, II 0.47, and RCV 70%. Conclusion In stable lung transplant patients, fluctuations in dd-cfDNA levels of up to 70% or levels less than 1% are within normal biological variation. With further validation, these thresholds may be incorporated into surveillance monitoring algorithms to identify potentially abnormal results indicating allograft dysfunction.

Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin-2, which is upregulated on immune cells in response to lung inflammation.What is the tolerability, safety, and effect on outcomes from efzofitimod in pulmonary sarcoidosis?A randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every four weeks for 24 weeks. Randomized patients (2:1) underwent a steroid taper to 5 mg/day by Week 8 or5 mg/day after Week 16. The primary endpoint was the incidence of adverse events; secondary endpoints included steroid reduction, change in lung function, and patient-reported outcomes on health-related quality of life scales.Thirty-seven patients received at least one dose of study medication. Efzofitimod was well tolerated at all doses, with no new or unexpected adverse events and no dose-dependent adverse event incidence. Average daily steroid doses through end of study were 6.8, 6.5 and 5.6 mg for the 1, 3 and 5 mg/kg groups compared to 7.2 mg for placebo, resulting in a baseline-adjusted relative steroid reduction of 5%, 9% and 22%, respectively. Clinically meaningful improvements were achieved across several patient reported outcomes, several of which reached statistical significance in the 5 mg/kg dose arm. A dose-dependent but non-significant trend toward improved lung function was also observed for 3 and 5 mg/kg.Efzofitimod was safe and well tolerated and associated with dose-dependent improvements of several clinically-relevant endpoints compared to placebo. The results of this study support further evaluation of efzofitimod in pulmonary sarcoidosis.

Respiratory viral infection (RVI) in lung transplant recipients (LTRs) is a risk for chronic lung allograft dysfunction (CLAD). We hypothesize that donor-derived cell-free DNA (%ddcfDNA), at the time of RVI predicts CLAD progression. We followed 39 LTRs with RVI enrolled in the Genomic Research Alliance for Transplantation for 1 year. Plasma %ddcfDNA was measured by shotgun sequencing, with high %ddcfDNA as ≥1% within 7 days of RVI. We examined %ddcfDNA, spirometry, and a composite (progression/failure) of CLAD stage progression, re-transplant, and death from respiratory failure. Fifty-nine RVI episodes, 38 low and 21 high %ddcfDNA were analyzed. High %ddcfDNA subjects had a greater median %FEV

Background Aberrations in the coagulation system have been implicated in the pathogenesis of interstitial lung disease (ILD). Anticoagulants have been proposed as a potential therapy in ILD; however, a randomized controlled trial examining warfarin as a treatment for IPF was terminated early due to increased death rates. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) could result in superior outcomes. Research Question The goal of this study was to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation Patient Registry. Study Design and Methods An analysis of all patients in the Pulmonary Fibrosis Foundation Patient Registry was performed. Patients were stratified into three groups: no anticoagulation, DOAC use, or warfarin use. Survival was analyzed by using both Kaplan-Meier curves and Cox proportional hazards models. Results Of 1,911 patients included in the analysis, 174 (9.1%) were given anticoagulants; 93 (4.9%) received DOACs, and 81 (4.2%) received warfarin. There was a twofold increased risk of death or transplant for patients receiving DOACS; for warfarin, the risk was over two and half times greater. DOACs were not associated with an increased risk of mortality following adjustment for confounding variables. However, even after adjustment, patients given the anticoagulant warfarin remained at increased risk of mortality. In patients with IPF, warfarin was associated with reduced transplant-free survival, but DOACs were not. There was no statistically significant difference in survival between those receiving warfarin and those receiving a DOAC. Interpretation The need for anticoagulation is associated with an increased risk for death or transplant in patients with ILD, in both the IPF and non-IPF population. Further research is required to determine if warfarin and DOACs present varying safety profiles in patients with ILD.

It has been suggested pleural effusions may develop in right heart failure in the absence of left heart disease. The incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension is uncertain. Patients with pulmonary arterial hypertension followed at our tertiary care center were reviewed. Survival was examined based on the subsequent development of a pleural effusion. A total of 191 patients with pulmonary arterial hypertension met the inclusion criteria. The prevalence of pleural effusions on initial assessment was 7.3%. Among patients without a pleural effusion on initial imaging and at least one follow-up computerized tomography ( N = 142), pleural effusion developed in 27.5% ( N = 39) of patients. No alternative etiology of the effusion was identified in 19 (48.7%) cases and effusions deemed related to pulmonary arterial hypertension occurred at an incident rate of 38.6 cases per 1000 person-years. Of these, 14 (73.7%) were bilateral, 3 (15.8%) were right-sided, and 2 (10.5%) were left-sided. Effusion size was trace or small in 18 patients (94.7%). Development of a new pleural effusion was associated with attenuated survival in unadjusted survival analysis (HR: 3.80; 95% CI: 1.55–9.31), multivariate analysis (HR: 5.13; 95% CI: 1.86–14.16), and after the multivariate model was adjusted for concomitant pericardial effusion (HR: 4.86; 95% CI: 1.51–15.71). Negative impact on survival remained unchanged when effusions more likely related to an alternative cause were removed from analysis. In conclusion, pleural effusions can complicate pulmonary arterial hypertension in the absence of left heart disease. These effusions are frequently small in size, bilateral in location, and their presence is associated with decreased survival. Attenuated survival appears independent of the risk associated with a new pericardial effusion.

Rationale: Video-assisted thoracoscopic surgery (VATS) remains the gold standard for interstitial lung disease (ILD) characterization when histology is deemed necessary. There is diminishing utiliz...

Purpose of review Need for intensive care in the patient with pulmonary arterial hypertension is associated with high mortality. This review will provide an overview of causes of ICU admission for patients with pulmonary hypertension and provide guidance on management. Recent findings There is a paucity of evidence-based medical literature on management of patients with pulmonary arterial hypertension. This article will summarize the available literature and expert guidance on the topic. Patients with pulmonary arterial hypertension may require ICU care as a direct consequence of decompensated right heart failure. Alternatively, patients with pulmonary arterial hypertension may be affected by the myriad of maladies encountered every day in the ICU including acute respiratory failure, septic shock, and gastrointestinal bleeding. The treatment plan should focus on identifying and treating the cause for decompensation. In addition, optimization of right ventricular preload, reduction of right ventricular afterload, correction of hypotension and augmentation of right ventricular inotropy should be considered. Summary The approach to ICU care of patients with pulmonary arterial hypertension requires special consideration with regard to intubation and mechanical ventilation and management of volume status and hemodynamics. Whenever possible, these patients should be transferred to centers with experience in treating this complex, vulnerable population.

Group 3 pulmonary hypertension (PH) is a broad category of PH caused by chronic lung diseases (CLD) including chronic obstructive pulmonary disease (COPD), diffuse parenchymal lung diseases (DPLD), sleep disordered breathing, chronic exposure to high altitudes and developmental abnormalities. It is the second most common type after group 2 PH which is secondary to left heart disease or pulmonary venous hypertension. Clinical features of group 3 PH are often difficult to discern from the signs and symptoms of the primary lung disease and most of the time, symptoms out of proportion to the severity of lung disease prompts evaluation for group 3 PH. In most patients with group 3 PH, the mean pulmonary artery pressure (mPAP) is usually mildly elevated. However, it is invariably associated with reduced functional ability, impaired quality of life, greater oxygen requirements and an increased risk of mortality. Transthoracic echocardiography is the best screening test to evaluate for underlying PH. Right heart catheterization (RHC) is the gold standard test for confirmation and is performed when significant PH is suspected and the patient's management will likely be influenced by the RHC results. Treatment of group 3 PH can be divided into four major categories- primary, adjunctive, PH-specific and treatment of refractory disease. Treatment of the primary lung disease is the most important aspect but supportive therapy including supplemental oxygen and pulmonary rehabilitation are also very essential. The role of pulmonary vasodilators in group 3 PH is still unclear and large, randomized controlled trials are in dire need.

The COVID-19 pandemic has caused acute lung injury in millions of individuals worldwide. Some patients develop COVID-related acute respiratory distress syndrome (CARDS) and cannot be liberated from mechanical ventilation. Others may develop post-COVID fibrosis, resulting in substantial disability and need for long-term supplemental oxygen. In both of these situations, treatment teams often inquire about the possibility of lung transplantation. In fact, lung transplantation has been successfully employed for both CARDS and post-COVID fibrosis in a limited number of patients worldwide. Lung transplantation after COVID infection presents a number of unique challenges that transplant programs must consider. In those with severe CARDS, the inability to conduct proper psychosocial evaluation and pretransplantation education, marked deconditioning from critical illness, and infectious concerns regarding viral reactivation are major hurdles. In those with post-COVID fibrosis, our limited knowledge about the natural history of recovery after COVID-19 infection is problematic. Increased knowledge of the likelihood and degree of recovery after COVID-19 acute lung injury is essential for appropriate decision-making with regard to transplantation. Transplant physicians must weigh the risks and benefits of lung transplantation differently in a post-COVID fibrosis patient who is likely to remain stable or gradually improve in comparison with a patient with a known progressive fibrosing interstitial lung disease (fILD). Clearly lung transplantation can be a life-saving therapeutic option for some patients with severe lung injury from COVID-19 infection. In this review, we discuss how lung transplant providers from a number of experienced centers approach lung transplantation for CARDS or post-COVID fibrosis.

As a marker of underlying lung allograft injury, donor-derived cell-free DNA (dd-cfDNA) may be used to identify episodes of acute allograft injury in lung transplant recipients. We investigated the utility of dd-cfDNA to monitor subjects at risk of acute rejection or infection in routine clinical practice.This multicenter, retrospective cohort study collected data from lung transplant recipients within 3 years of transplant at 4 centers between March 24, 2020 and September 1, 2020. During this period, as part of routine care during the COVID-19 pandemic, these centers implemented a home-based surveillance program using plasma dd-cfDNA in preference to surveillance bronchoscopy. Dd-cfDNA was used to detect acute lung allograft dysfunction (ALAD) - a composite endpoint of acute rejection and infection. dd-cfDNA levels in patients with ALAD were compared to stable patients. The performance characteristics of dd-cfDNA ≥ 1.0% to detect ALAD were estimated.A total of 175 patients underwent 380 dd-cfDNA measurements, of which 290 were for routine surveillance purposes. dd-cfDNA was higher in patients with ALAD than stable patients (Median (IQR) 1.7% (0.63, 3.1) vs 0.35% (0.22, 0.79), p0.001). As an indication of underlying ALAD during surveillance testing, the estimated sensitivity of dd-cfDNA ≥1% was 73.9%, specificity of 87.7%, positive predictive value of 43.4% and negative predictive value of 96.5%.dd-cfDNA identified acute lung allograft dysfunction in asymptomatic lung transplant patients that may not have been identified by using a clinically indicated biopsy strategy alone. dd-cfDNA1.0% may be useful in ruling out acute rejection and infection, supporting its use as a potential noninvasive marker for surveillance monitoring.

BackgroundConvalescent plasma therapy (CPT) and remdesivir (REM) have been approved for investigational use to treat coronavirus disease 2019 (COVID-19) in Nepal.MethodsIn this prospective, multicentered study, we evaluated the safety and outcomes of treatment with CPT and/or REM in 1315 hospitalized COVID-19 patients over 18 years in 31 hospitals across Nepal. REM was administered to patients with moderate, severe, or life-threatening infection. CPT was administered to patients with severe to life-threatening infections who were at high risk for progression or clinical worsening despite REM. Clinical findings and outcomes were recorded until discharge or death.ResultsPatients were classified as having moderate (24.2%), severe (64%), or life-threatening (11.7%) COVID-19 infection. The majority of CPT and CPT + REM recipients had severe to life-threatening infections (CPT 98.3%; CPT + REM 92.1%) and were admitted to the intensive care unit (ICU; CPT 91.8%; CPT + REM 94.6%) compared with those who received REM alone (73.3% and 57.5%, respectively). Of 1083 patients with reported outcomes, 78.4% were discharged and 21.6% died. The discharge rate was 84% for REM (n = 910), 39% for CPT (n = 59), and 54.4% for CPT + REM (n = 114) recipients. In a logistic model comparing death vs discharge and adjusted for age, gender, steroid use, and severity, the predicted margin for discharge was higher for recipients of remdesivir alone (0.82; 95% CI, 0.79–0.84) compared with CPT (0.58; 95% CI, 0.47–0.70) and CPT + REM (0.67; 95% CI, 0.60–0.74) recipients. Adverse events of remdesivir and CPT were reported in ConclusionsThis study demonstrates a safe rollout of CPT and REM in a resource-limited setting. Remdesivir recipients had less severe infection and better outcomes.ClinicalTrials.gov identifier. NCT04570982.

Background Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. Methods We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. Results A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs -2.6 ± 0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. Conclusion For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. Clinical Trials Registration Clinicaltrials.gov, NCT04579393.

We present a case of sarcoidosis presenting as unilateral forearm swelling. A 65-year-old male with a long history of asthma presented with unexplained left forearm and hand swelling. Over many years, chest imaging had been devoid of adenopathy or parenchymal findings suspicious for sarcoid, until after the extremity findings emerged. The patient was diagnosed based on subcutaneous, dermal and mediastinal lymph node histopathology. Sarcoid presenting with isolated extremity findings prior to more typical pulmonary manifestations is rare even for cutaneous or soft tissue sarcoid, highlighting the need to maintain a high index of suspicion for sarcoidosis.

Rationale: Interpreting the radiologic data in conjunction with an objective clinical score could help to harmonize idiopathic pulmonary fibrosis (IPF) diagnosis and improve accuracy. Objectives: We sought to establish and validate a multivariable objective scoring model based on clinical parameters by stratifying the risk of patients having IPF diagnosed versus having other forms of interstitial lung disease (ILD) diagnosis. Methods: A clinical score was derived from review of patients evaluated at the Inova Fairfax ILD Program and validated in three distinct cohorts. On the basis of known IPF clinical characteristics, a multivariable model was created and assessed by using receiver operating characteristic curves. Results: There were 844 patients with ILD with either IPF (n = 347, 41%) or non-IPF ILD (n = 497, 59%) diagnosis. On the basis of calculated odds ratios, a score was assigned to each of the following clinical parameters: age, sex, smoking history, race or ethnicity, ILD family history, exposures, presence of connective tissue disease signs or symptoms, and velcro crackles. The final Fairfax IPF Clinical Score (FICS) ranged from 1 to 25. The clinical diagnostic score system was accurate in predicting IPF, as measured by the area under the curve (0.88) in the derivation cohort, with similar areas under the curve of 0.91, 0.81, and 0.71 being demonstrated in the respective validation cohorts. Conclusions: The FICS appears to be an accurate tool for estimating the pretest probability of IPF in patients with ILD. How the FICS performs in conjunction with the various high-resolution computed tomographic patterns remains to be determined. This model could ultimately be useful for increasing the degree of confidence in the final diagnosis and could help to obviate the need for lung biopsy in cases with non-usual interstitial pneumonia patterns on high-resolution computed tomographic images., Philippe Foundation; Assistance Publique-Hopitaux de Paris, Supported by Assistance Publique-Hopitaux de Paris and the Philippe Foundation funding (J.P.).

Background: In the absence of legal provision for emergency use authorization, Nepal government approved convalescent plasma therapy (CPT) and remdesivir for investigational use to treat COVID-19. Methods: This prospective, multicentered, observational study describes the safety and outcomes of hospitalized CPT and remdesivir treated COVID-19 patients. The study enrolled 1315 patients from 31 hospitals across Nepal. Patients over 18 years age received remdesivir, CPT, or both. Clinical findings, lab results, adverse events, and outcomes were recorded. Findings: Patients were classified as having moderate (24.2%), severe (64%) or life-threatening (11.7%) COVID-19. Of 1083 patients with reported outcomes, 78.4% were discharged (74% in good condition, 4.4% with disability) and 21.6% died. Discharge rates were 84% for remdesivir only recipients (N=910), 39% for CPT only recipients (N=59), and 54.4% for CPT+REM (N=114) recipients. The vast majority of CPT and CPT+REM recipients had severe to life-threatening infections (CPT 98.3%; CPT+REM 92.1%) and were admitted to the ICU (CPT 91.8%; CPT+REM 94.6%) compared to REM alone recipients (73.3% and 57.5%, respectively). In a logistic model comparing death vs discharge and adjusted for age, gender, steroid use, and severity, the predicted margin for discharge was higher for remdesivir alone recipients (0.82; 95%CI 0.79-0.84) compared to CPT (0.58; 95%CI 0.47-0.70) or CPT+REM (0.67; 95%CI 0.60-0.74) recipients. Adverse events of Remdesivir and CPT were reported in

Additional file 1: Table S1. Clinical, physiological and functional characteristics of IPF patients depending on when they develop severe functional impairment (FVC ≤ 50% and/or DLco ≤ 30% predicted). Table S2. Clinical, physiological and functional characteristics of IPF patients depending on whether they are treated or not by antifibrotic therapies.

PurposeThe outcomes of patients requiring invasive mechanical ventilation for COVID-19 remain poorly defined. We sought to determine clinical characteristics and outcomes of patients with COVID-19 managed with invasive mechanical ventilation in an appropriately resourced US health care system.MethodsOutcomes of COVID-19 infected patients requiring mechanical ventilation treated within the Inova Health System between March 5, 2020 and April 26, 2020 were evaluated through an electronic medical record review.Results1023 COVID-19 positive patients were admitted to the Inova Health System during the study period. Of these, 165 (16.1%) were managed with invasive mechanical ventilation. At the time of data censoring, 63/165 patients (38.1%) had died and 102/165 (61.8%) were still alive. Of the surviving 102 patients, 17 (10.3%) remained on mechanical ventilation, 51 (30.9%) were extubated but remained hospitalized, and 34 (20.6%) had been discharged. Deceased patients were older (median age of 66 vs. 55, p ConclusionMortality of patients with COVID-19 requiring invasive mechanical ventilation is high, with particularly daunting mortality seen in patients of advanced age, even in a well-resourced health care system. A substantial proportion of patients requiring invasive mechanical ventilation were not of advanced age, and this group had a reasonable chance for recovery.

Supplemental material, Author_Response for HRCT evaluation of patients with interstitial lung disease: comparison of the 2018 and 2011 diagnostic guidelines by Steven D. Nathan, Jean Pastre, Inga Ksovreli, Scott Barnett, Christopher King, Shambhu Aryal, Kareem Ahmad, Cesar Fukuda, Vijaya Ramalingam and Jonathan H. Chung in Therapeutic Advances in Respiratory Disease

Supplemental material, Reviewer_3_v.1 for HRCT evaluation of patients with interstitial lung disease: comparison of the 2018 and 2011 diagnostic guidelines by Steven D. Nathan, Jean Pastre, Inga Ksovreli, Scott Barnett, Christopher King, Shambhu Aryal, Kareem Ahmad, Cesar Fukuda, Vijaya Ramalingam and Jonathan H. Chung in Therapeutic Advances in Respiratory Disease

Purpose of review Lung transplantation is a life-saving treatment for several end stage lung diseases. Over the last two decades, the number of lung transplantation performed worldwide has steadily increased but several thousand people still die every year waiting for lung transplantation. However, the optimal procedure for lung transplantation in non-septic lung conditions remains debatable. Recent findings In pulmonary fibrosis and COPD, many recent studies suggest superiority of bilateral lung transplantation over single lung transplantation when long-term survival is evaluated; consequently, bilateral lung transplantation has been favored by many lung transplantation centers. However, the quality of evidence to support the superiority of bilateral lung transplantation remains low in the absence of prospective studies, and other available studies do not show differences in outcomes between the two types of procedure. Summary In the absence of good high quality evidence, it is difficult to make strong general recommendations for the type of lung transplant, and the decision often has to be individualized. However, the number of recipients on the wait list continues to surpass the amount of available organs and due consideration needs to be given to single lung transplantation as an option whenever possible.

Purpose Prior studies have demonstrated that percentage donor-derived cell-free DNA (%dd-cfDNA) in lung transplant patients may serve as a noninvasive marker of allograft injury and aid in the detection of acute allograft rejection, infection and chronic lung allograft dysfunction (CLAD). Clinical interpretation of %dd-cfDNA values require an understanding of its normal biological variation in stable lung transplant patients in order to identify abnormal results that may indicate the presence of allograft dysfunction. This study establishes the biological variation and reference change values (RCV) of %dd-cfDNA in lung transplant patients using an analytically validated assay with an established analytic coefficient of variation (CVA) of 6.8%. Methods Levels of plasma %dd-cfDNA (Allosure®) were analyzed from a cohort of patients at 4 lung transplant centers using %ddcfDNA as a method to monitor for allograft rejection in place of surveillance transbronchial biopsy. Patients with stable allograft function and ≥ 3 %dd-cfDNA samples were included. Stable patients were defined as having no evidence of infection, rejection, symptoms or documented decline in forced expiratory volume in 1 second (FEV1) > 10% from baseline. The AlloSure assay, a next-generation sequencing-based approach, was used to measure %dd-cfDNA in the plasma. Intraindividual coefficient of variation (CVI), interindividual CV (CVG), the index of individuality (II) and the RCV were calculated. Results 35 patients with a combined 124 %dd-cfDNA samples were included in the final analysis. 57% were men, the mean age was 59 years and 77% had bilateral lung transplants. The median %dd-cfDNA was 0.31% (interquartile range 0.18% - 0.68%), the 97.5th percentile and 95th percentile were 1.3% and 1.0% respectively. In 30 patients with an average of 3.7 tests, the CVI was 25%, the CVG was 19%, the II was 1.3 and the RCV was 72%. Conclusion In stable lung transplant patients, fluctuations in %dd-cfDNA levels of up 72% or levels less than 1% are within normal biological variation. With further validation, these thresholds may be incorporated into surveillance monitoring algorithms to identify potentially abnormal results indicating allograft dysfunction.

Introduction L’interpretation des donnees radiologiques en association avec les donnees cliniques pourrait ameliorer la precision diagnostique dans la fibrose pulmonaire idiopathique (FPI). Dans cette hypothese, nous avons souhaite mettre en place un score base sur des parametres cliniques permettant d’evaluer la probabilite de FPI chez des patients se presentant pour le bilan d’une pneumopathie interstitielle diffuse (PID). Methodes Le modele de score clinique etait etabli par analyse des dossiers de patients s’etant presentes entre 2012 et 2019 au Inova Advanced Lung Disease Program (Fairfax, Virginie, USA) pour une PID. Seuls les patients avec un diagnostic etabli avec un haut degre de confiance et en accord avec les recommandations internationales sur la FPI ou les autres PID etaient inclus. 8 parametres cliniques etaient retenus pour la mise en place du modele. Le modele multivarie etait etabli par analyse des caracteristiques de la courbe ROC puis ensuite teste dans trois cohortes de validations internationales differentes. Resultats 844 patients atteints de PID et qui presentaient un diagnostic classable entre FPI (347, 41 %) ou PID non-FPI (497, 59 %) ont ete evalues pendant cette periode. Sur la base de rapports de cote calcules pour 8 parametres cliniques suivants, un index chiffre etait assigne a chaque variable: âge ( 80: +4), sujet masculin (+3), antecedent de tabagisme (+2), Caucasien (+2), antecedent familial de PID (+5), exposition respiratoire (−1), signe de connectivite (−3), crepitants velcro (+4). Le score final etait obtenu par addition des points et variait de −5 a 20. Ce score clinique presentait une precision diagnostique evaluee par l’aire sous la courbe (ASC) de 0,88. Un score de 5 points ou moins etait associe a une probabilite de FPI de 4 %, un score de 6–10: 29 %, 11–15: 75 % et > 15: 97 %. Les caracteristiques de la courbe ROC etaient comparable dans les cohortes internationales de validation (n = 694 patients, ASC: 0,87). Conclusion Ce modele de score clinique apparait comme un outil precis et simple pour estimer la probabilite pretest de FPI parmi les patients avec une PID. Son impact utilise en conjonction avec l’imagerie reste a determiner. Ce modele pourrait in fine etre utile pour augmenter le degre de confiance dans le diagnostic final, homogeneiser les DMD, diminuer le nombre de cas « inclassable » ou eviter le recours a une biopsie pulmonaire si la probabilite pretest de FPI etait elevee.