Monogenic gene variants in lung transplant recipients with usual interstitial pneumonia

Question addressed by the studyThe prevalence of monogenic disease-causing gene variants in lung-transplant recipients with idiopathic pulmonary fibrosis is not fully known. Their impact on clinical outcomes before and after transplantation requires more evidence.Patients and MethodsWe retrospectively performed sequence analysis of genes associated with pulmonary fibrosis in a cohort of 23 patients with histologically confirmed usual interstitial pneumonia that had previously undergone double lung transplantation. We evaluated the impact of confirmed molecular diagnoses on disease progression, clinical outcomes and incidence of acute rejection or chronic lung allograft dysfunction after transplantation.ResultsFifteen patients out of 23 (65%) had a variant in a gene associated with interstitial lung disease. Eleven patients (48%) received a molecular diagnosis, of which nine involved genes for telomerase function. Five diagnostic variants were found in the gene for Telomerase reverse transcriptase. Two of these variants, p.(Asp684Gly) and p.(Arg774*), seemed to be enriched in Finnish lung-transplant recipients. Disease progression and the incidence of acute rejection and chronic lung allograft dysfunction was similar between patients with telomere-related disease and the rest of the study population. The incidence of renal or bone marrow insufficiency or skin malignancies did not differ between the groups.Answer to the questionGenetic variants are common in lung transplant recipients with pulmonary fibrosis and are most often related to telomerase function. A molecular diagnosis for telomeropathy does not seem to impact disease progression or the risk of complications or allograft dysfunction after transplantation.

Clinical, radiologic, and morphological diagnosis of hypersensitivity pneumonitis

Aim. To study the relationship between clinical, radiologic, and morphological features in nonfibrotic and fibrotic hypersensitivity pneumonitis.Materials and methods. Clinical symptoms, data of high-resolution computed tomography, parameters of external respiration, and histological changes in the lung tissue obtained via open and transbronchial biopsies were studied retrospectively in 175 patients with hypersensitivity pneumonitis (HP). Statistical analysis was performed using the Statistica software.Results. We found that the clinical error rate in the diagnosis of HP was 84.5%, among pathologists – 92%. Among all the variants of HP, the most common was fibrotic HP. It was shown that non-necrotizing granulomas and giant cells in the cavities of the alveoli, microcells, and interalveolar septa were more typical of nonfibrotic HP. In fibrotic HP, peribronchial fibrosis, smooth muscle metaplasia in fibrotic areas, and the presence of fibroblastic foci in the walls of terminal bronchioles are signs of differential diagnosis with usual interstitial pneumonia. The classical triad of histological signs was observed in 19.2% of patients with nonfibrotic HP and in 5.6% of patients with fibrotic HP.Conclusion. Diagnosis of HP is complex and should be based on a multidisciplinary approach involving clinicians (pulmonologists), radiologists, functional diagnostics specialists, and pathologists. In this case, it is imperative to take into account and identify factors causing development of the disease, as well as the age of patients.

Role of HRCT in evaluation of Interstitial Lung Disease

In this study, HRCT is the examination technique of choice as it is quickly accomplished, readily available and does not require ancillary studies using other imaging technologies in most cases. In this given study, A total of 40 patients were included in which 16 patients were found to be having ILDs , there were 10 male patients (62.5%) and 6 were female patients i.e., (37.5%) of total number of patients .Idiopathic pulmonary fibrosis were found in 3 (18.75%) patients, Usual interstitial pneumonia in 2 (12.5%) patients, Chronic Hypersensitive pneumonitis in 1 (6.25%) patient , Fibrotic hypersensitive pneumonitis in 4 (25%) patients and Pulmonary interstitial edema in 6 (37.5%). The maximum patients were found in pulmonary interstitial edema and minimum patients in Chronic Hypersensitive pneumonitis, the highest number of patients with interstitial lung disease were from the 60-80 Years age group category, which was 8 Out of 16 i.e. 50% of the total number of the patients and no patients were found from the age group 0-18 years age group and 80-100 years age group.

Differences in Baseline Characteristics and Access to Treatment of Newly Diagnosed Patients With IPF in the EMPIRE Countries

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with poor prognosis. The diagnosis and treatment possibilities are dependent on the health systems of countries. Hence, comparison among countries is difficult due to data heterogeneity. Our aim was to analyse patients with IPF in Central and Eastern Europe using the uniform data from the European Multipartner IPF registry (EMPIRE), which at the time of analysis involved 10 countries. Newly diagnosed IPF patients (N = 2,492, between March 6, 2012 and May 12, 2020) from Czech Republic (N = 971, 39.0%), Turkey (N = 505, 20.3%), Poland (N = 285, 11.4%), Hungary (N = 216, 8.7%), Slovakia (N = 149, 6.0%), Israel (N = 120, 4.8%), Serbia (N = 95, 3.8%), Croatia (N = 87, 3.5%), Austria (N = 55, 2.2%), and Bulgaria (N = 9, 0.4%) were included, and Macedonia, while a member of the registry, was excluded from this analysis due to low number of cases (N = 5) at this timepoint. Baseline characteristics, smoking habit, comorbidities, lung function values, CO diffusion capacity, high-resolution CT (HRCT) pattern, and treatment data were analysed. Patients were significantly older in Austria than in the Czech Republic, Turkey, Hungary, Slovakia, Israel, and Serbia. Ever smokers were most common in Croatia (84.1%) and least frequent in Serbia (39.2%) and Slovakia (42.6%). The baseline forced vital capacity (FVC) was >80% in 44.6% of the patients, between 50 and 80% in 49.3%, and <50% in 6.1%. Most IPF patients with FVC >80% were registered in Poland (63%), while the least in Israel (25%). A typical usual interstitial pneumonia (UIP) pattern was present in 67.6% of all patients, ranging from 43.5% (Austria) to 77.2% (Poland). The majority of patients received antifibrotic therapy (64.5%); 37.4% used pirfenidone (range 7.4–39.8% between countries); and 34.9% nintedanib (range 12.6–56.0% between countries) treatment. In 6.8% of the cases, a therapy switch was initiated between the 2 antifibrotic agents. Significant differences in IPF patient characteristics and access to antifibrotic therapies exist in EMPIRE countries, which needs further investigation and strategies to improve and harmonize patient care and therapy availability in this region.

Development and external validation of a deep learning-based computed tomography classification system for COVID-19

Rationale: Currently available machine learning models for diagnosing COVID-19 based on computed tomography (CT) images are limited due to concerns regarding methodological flaws or underlying biases in the evaluation process. Objectives: We aimed to develop and externally validate a novel machine learning model that can classify CT image findings as positive or negative for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR).Methods: We used 3128 images from a wide variety of two-gate data sources for the development and ablation study of the machine learning model. A total of 633 COVID-19 cases and 2295 non-COVID-19 cases were included in the study. We randomly divided cases into a development set and ablation set at a ratio of 8:2. For the ablation study, we used another dataset including 150 cases of interstitial pneumonia among non-COVID-19 images. For external validation, we used 893 images from 740 consecutive patients at 11 acute care hospitals suspected of having COVID-19 at the time of diagnosis. The dataset included 343 COVID-19 patients. The reference standard was RT-PCR.Result: In ablation study, using interstitial pneumonia images, the specificity of the model were 0.986 for usual interstitial pneumonia pattern, 0.820 for non-specific interstitial pneumonia pattern, 0.400 for organizing pneumonia pattern. In the external validation study, the sensitivity and specificity of the model were 0.869 and 0.432, respectively, at the low-level cutoff, and 0.724 and 0.721, respectively, at the high-level cutoff.Conclusions: Our machine learning model exhibited a high sensitivity in external validation datasets and may assist physicians to rule out COVID-19 diagnosis in a timely manner. Further studies are warranted to improve model specificity.

High-Resolution Computed Tomography and Lung Ultrasound in Patients with Systemic Sclerosis: Which One to Choose?

Imaging plays a pivotal role in systemic sclerosis for both diagnosis management of pulmonary complications, and high-resolution computed tomography (HRCT) is the most sensitive technique for the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Indeed, several studies have demonstrated that HRCT helps radiologists and clinicians to make a correct diagnosis on the basis of recognised typical patterns for SSc-ILD. Most SSc patients affected by ILD have a non-specific interstitial pneumonia pattern (NISP) on HRCT scan, whilst a minority of cases fulfil the criteria for usual interstitial pneumonia (UIP). Moreover, several recent studies have demonstrated that lung ultrasound (LUS) is an emergent tool in SSc diagnosis and follow-up, although its role is still to be confirmed. Therefore, this article aims at evaluating the role of LUS in SSc screening, aimed at limiting the use of CT to selected cases.

Epidemiology of ILDs and their progressive-fibrosing behaviour in six European countries

The PERSEIDS study aimed to estimate incidence/prevalence of interstitial lung diseases (ILDs), fibrosing Interstitial lung diseases (F-ILDs), idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated ILD (SSc-ILD), other non-IPF F-ILDs and their progressive-fibrosing (PF) forms in six European countries, as current data are scarce.This retrospective, two-phase study used aggregate data (2014–2018). In Phase 1, incident/prevalent cases of ILDs above were identified from clinical databases through an algorithm based on codes/keywords, and incidence/prevalence was estimated. For non-IPF F–ILDs, the relative percentage of subtypes was also determined. In Phase 2, a subset of non-IPF F-ILD cases was manually reviewed to determine the percentage of PF behaviour and usual interstitial pneumonia-like (UIP-like) pattern. A weighted mean percentage of progression was calculated for each country and used to extrapolate incidence/prevalence of progressive-fibrosing ILDs (PF–ILDs).In 2018, incidence/105 person-years ranged between 9.4–83.6(ILDs), 7.7–76.2(F-ILDs), 0.4–10.3(IPF), 6.6–71.7(non-IPF F-ILDs) and 0.3–1.5(SSc-ILD); and prevalence/105 persons ranged between 33.6–247.4(ILDs), 26.7–236.8(F-ILDs), 2.8–31.0(IPF), 22.3–205.8(non-IPF F-ILDs) and 1.4–10.1(SSc-ILD). Among non-IPF F-ILDs, sarcoidosis was the most frequent subtype. PF behaviour and UIP-like pattern were present in a third of non-IPF F-ILD cases each and hypersensitivity pneumonitis showed the highest percentage of progressive behaviour. Incidence of PF-ILDs ranged between 2.1–14.5/105 person-years, and prevalence between 6.9–78.0/105 persons.To our knowledge, PERSEIDS is the first study assessing incidence, prevalence and rate of progression of ILDs across several European countries. Still below the threshold for orphan diseases, the estimates obtained were higher and more variable than reported in previous studies, but differences in study design/population must be considered.

Central, peripheral ECMO or CPB? Comparsion between circulatory support methods used during lung transplantation

Background Chronic obstructive pulmonary disease, cystic fibrosis and usual interstitial pneumonia are three most common indications for lung transplantation (LuTx) in Poland. As a result of irreversible destruction of pulmonary parenchyma and extended respiratory insufficiency that appear afterwards, it is crucial to estimate the reserve of gas exchange in each lung before and during surgery. Altering conditions of gas exchange require adaptation in circulatory system as well. In some of the cases the use of extracorporeal life support appears to be necessary to undergo the transplantation successfully. Cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) used during operation allow to replace the function of heart and lung, but they are also related to complications in the form of acute kidney failure, bleeding, heart arrhythmias or thromboembolic complications. Methods We reviewed 77 LuTx from 2009 to 2020 performed at the Department of Thoracic Surgery and Transplantation. 40/77 (51%) patients required intraoperative extracorporeal assistance: 8 required CBP and 32 required ECMO. In the ECMO group 14/32 (44%) patients had peripheral cannulation and 18/32 (56%) had central one. We have calculated the survival rates and reviewed postoperative complications after lung transplantations. Cumulative Kaplan–Meier survival curves were calculated. Differences between the groups were evaluated by the Chi- square analysis for discontinuous variables and t-test for continuous variables. Results The use of intraoperative central extracorporeal membrane oxygenator was associated with increased survival rates comparing to patients without external support (30-days, 1-year, 3-years, 5-years rates: 78%, 66%, 66%, 66% vs 83%, 65%, 59%, 44% respectively). Furthermore, survival was enhanced comparing to peripheral ECMO or cardiopulmonary bypass as well (50%, 41%, 41%, 33%; 75%, 50%, 50%, 38% respectively). Acute kidney injury and thromboembolic complications occurred statistically more often in case of patients that underwent lung transplantation with support devices (p = 0.005, p = 0.02 respectively). Frequency of other complications was comparable among groups. Conclusions The use of central extracorporeal membrane oxygenation should be favorized over peripheral cannulation or cardiopulmonary bypass. CPB should be no longer used during LuTx. Trial registration Not applicable.