OAR@UM Collection:

Genetic ghosts in the lung : post- COVID fibrosis unveils CTC1 mutation

2026-01-01T00:00:00Z

Title: Genetic ghosts in the lung : post- COVID fibrosis unveils CTC1 mutation Authors: Azzopardi, Christine; Azzopardi, Joelle; Fsadni, Peter; Conti, Luca Abstract: Background: Familial pulmonary fibrosis (FPF) accounts for 10%-20% of idiopathic pulmonary fibrosis cases and is associated with mutations in telomere-related genes, including TERT, TERC, RTEL1, PARN, and, more recently, CTC1. Telomere dysfunction predisposes to progressive fibrotic interstitial lung disease (ILD) and may increase susceptibility to environmental triggers. Emerging evidence suggests that COVID-19 pneumonitis may unmask or accelerate fibrosis in genetically predisposed individuals, though a causal relationship has not been established. We report a case of genetically confirmed FPF due to a likely pathogenic CTC1 mutation presenting with progressive post-COVID pulmonary fibrosis.; Case Presentation: A 59-year-old woman with post-COVID pulmonary fibrosis presented with progressive dyspnea, orthopnea, and functional decline over 6 months. She required long-term oxygen therapy (5 l/min). Family history was significant for two first-degree relatives with usual interstitial pneumonia. Pulmonary function tests showed severe restriction (FVC 48%, diffusing capacity 19%). Imaging evolved from organizing pneumonia during acute COVID-19 to established bilateral fibrotic ILD with traction bronchiectasis and features suggestive of pulmonary hypertension (grade 3), confirmed on right heart catheterization (mean PAP 38 mmHg). Autoimmune workup was largely negative aside from anti-nuclear antibody positivity. Pirfenidone was discontinued due to hepatotoxicity. Genetic testing identified a heterozygous CTC1 variant (c.2518C>T; p.Arg840Trp), classified as likely pathogenic. She was commenced on nintedanib and referred for lung transplantation.; Conclusion: This case highlights the interplay between telomere-related genetic predisposition and viral injury in FPF. COVID-19 may have unmasked or accelerated fibrotic progression in susceptible individuals, though this association remains observational. Early genetic testing, multidisciplinary management, and timely transplant referral are crucial, with careful monitoring for treatment-related and post-transplant complications.

Association between a novel adult congenital heart disease-specific patient-reported health status metric and objective clinical status

2026-01-01T00:00:00Z

Title: Association between a novel adult congenital heart disease-specific patient-reported health status metric and objective clinical status Authors: Mi Ko, Jong; Kutty, Shelby; Van Bulck, Liesbet; Jackson, Jamie L.; Caruana, Maryanne; Jameson, Susan M.; Mahadevan, Vaikom S.; Moon, Philip; Cedars, Ari M. Abstract: BACKGROUND:; Although disease-specific patient-reported outcomes (PROs) are well accepted as direct and indirect clinical outcomes in various diseases, data on PRO performance in adult congenital heart disease (ACHD) are limited to nondisease-specific metrics. We, therefore, investigated the association between responses to a novel ACHD-specific PRO metric and both clinical variables and gold standard PROs.; METHODS:; We assessed the association between patient-perceived health status as assessed by the summary score of the Adult Congenital Heart Disease Patient-Reported Outcome Version 1 (ACHD PRO V.1) and hospital admission within the preceding 5 years in the English-speaking subgroup of an international cohort of patients with ACHD enrolled in APPROACH IS-II between February 10, 2019, and December 14, 2022. We also examined the relationship between ACHD PRO V.1 domain scores and domain-relevant clinical variables, the Linear Analog Scale Quality of Life, the Patient Health Questionnaire-8, and the Generalized Anxiety Disorder-7.; RESULTS:; The analysis includes 333 patients. Both unadjusted and adjusted models revealed that worse patient-perceived health status was associated with unplanned hospital admission (adjusted β, −5.7 [95% CI, −9.9 to −1.6]; P=0.007). Univariate analysis indicated a strong association between ACHD PRO V.1 domains and relevant clinical variables. A moderate correlation was found between the QOL and anxiety/depression domains and their corresponding gold standard (r=0.467, P<0.001 with the Linear Analog Scale Quality of Life; r=−0.581, P<0.001 with the Patient Health Questionnaire-8; and r=−0.540, P<0.001 with the Generalized Anxiety Disorder-7).; CONCLUSIONS:; A lower ACHD PRO V.1 summary score is associated with a history of unplanned cardiac admission. In addition, the ACHD PRO V.1 domains show good content validity by comparison with relevant clinical conditions and gold standard PROs. These data support the use of the ACHD PRO V.1 as a direct and surrogate clinical outcome in ACHD.

Association between a novel adult congenital heart disease patient-reported outcome metric and New York heart association functional classification

2026-01-01T00:00:00Z

Title: Association between a novel adult congenital heart disease patient-reported outcome metric and New York heart association functional classification Authors: Amir, Rawan; Mi Ko, Jong; Kutty, Shelby; Van Bulck, Liesbet; Jackson, Jamie L.; Caruana, Maryanne; Jameson, Susan M.; Mahadevan, Vaikom S.; Moons, Philip; Cedars, Ari Abstract: Patient-reported outcomes (PROs) are important for clinical care. As part of the Adults with Congenital Heart Disease International Study- II, we included an English language version of the novel adult congenital heart disease (ACHD)—specific PRO metric, the ACHD PRO, for distribution at English-speaking sites. We found that ACHD PRO scores correlate with New York Heart Association functional class, with an 11-point change in summary score reflecting a 1- category change in New York Heart Association class. These results provide further validation of the ACHD PRO as a tool and suggest clinically meaningful thresholds for differences in the ACHD PRO summary score.

Endotoxin exposure associated with respiratory health among European schoolchildren : the SINPHONIE study

2025-01-01T00:00:00Z

Title: Endotoxin exposure associated with respiratory health among European schoolchildren : the SINPHONIE study Authors: Baloch, Ramen Munir; Magyar, Donát; Rudnai, Peter; Pándics, Tamás; Remény-Nagy, Zsuzsanna; Moshammer, Hanns; Leppänen, Hanna; Hyvärinen, Anne; Täubel, Martin; Norbäck, Dan; Gabriel, Marta; Maio, Sara; Baldacci, Sandra; Sarno, Giuseppe; Viegi, Giovanni; Csobod, Eva; de Oliveira Fernandesi, Eduardo; Annesi-Maesano, Isabella; Szuppinger, Péter; Prokai, Réka; Farkas, Petur; Fuzi, Cecilia; Cani, Eduart; Draganic, Jasna; Réka Mogyorosy, Eszter; Korac, Zorica; Ventura, Gabriela; Madureira, Joana; Paciência, Inês; Martins, Anabela; Pereira, Ricardo; Ramos, Elisabete; Páldy, Anna; Dura, Gyula; Beregszászi, Tímea; Vaskövi, Éva; Magyar, Donát; Pándics, Tamás; Remény-Nagy, Zsuzsanna; Szentmihályi, Renáta; Udvardy, Orsolya; Varró, Mihály J.; Kephalopoulos, Stylianos; Kotzias, Dimitrios; Barrero-Moreno, Josefa; Mehmeti, Rahmije; Vilic, Aida; Maestro, Daniel; Hohenblum, Philipp; Goelen, Eddy; Stranger, Marianne; Spruy, Maarten; Sidjimov, Momchil; Hadjipanayis, Adamos; Katsonouri-Sazeides, Andromachi; Demetriou, Eleni; Kubinova, Ruzana; Kazmarová, Helena; Dlouha, Beatricia; Kotlík, Bohumil; Vabar, Helen; Ruut, Juri; Metus, Meelis; Rand, Kristiina; Järviste, Antonina; Nevalainen, Aino; Hyvarinen, Anne; Täubel, Martin; Järvi, Kati; Mandin, Corinne; Berthineau, Bruno; Moriske, Heinz-Joern; Giacomini, Marcia; Neumann, Anett; Bartzis, John; Kalimeri, Krystallia; Saraga, Dikaia; Santamouris, Mattheos; Assimakopoulos, Niki; Asimakopoulos, Vasiliki; Cattaneo, Andrea; Pulvirenti, Salvatore; Vercelli, Franco; Strangi, Fabio; Omeri, Elida; Piazza, Silvia; D’Alcamo, Andrea; Fanetti, Anna Clara; Sestini, Piersante; Kouri, Magdalini; Viegi, Giovanni; Sarno, Giuseppe; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Franzitta, Vincenzo; Bucchieri, Salvatore; Cibella, Fabio; Simoni, Marzia; Maugeri, Salvatore; Neri, Margherita; Martuzevičius, Dainius; Krugly, Edvinas; Montefort, Stephen; Fsadni, Peter; Brewczyński, Piotr Z.; Krakowiak, Ewa; Kurek, Jolanta; Kubarek, Elżbieta; Wlazło, Agnieszka; Borrego, Carlos; Alves, Célia; Valente, Joana; Gurzau, Eugen; Rosu, Cristina; Popita, Gabriela; Neamtiu, Iulia; Neagu, Cristina; Norback, Dan; Bohms, Michel; Van Den Hazel, Peter; Cassee, Flemming; de Bruin, Yuri Bruinen; Bartonova, Alena; Yang, Aileen; Halzlová, Katarína; Jajcaj, Michal; Kániková, Milada; Miklankova, Olga; Vítkivá, Marianna; Jovasević-Stojanovic, Milena; Zivkovic, Marija; Stevanovic, Zarko; Lazovic, Ivan; Stevanovic, Zana; Zivkovic, Zorica; Cerovic, Sofija; Jocic- Stojanovic, Jasmina; Mumovic, Dejan; Tarttelin, Paula; Chatzidiakou, Lia; Chatzidiakou, Evangelia Abstract: Background: Evidence on the association between endotoxin exposure and respiratory health in children remains inconsistent, with limited research addressing school environments— key settings for daily exposure. This study investigates the relationship between classroom endotoxin levels and respiratory health among European schoolchildren.; Methods: Within the EU-funded SINPHONIE project, endotoxin concentrations were measured in 285 classrooms across 102 schools in 22 European countries. A total of 5,140 children completed a standardized health questionnaire; 4,633 had endotoxin data, 4,170 performed spirometry, and 746 underwent fractioned exhaled nitric oxide (FeNO) testing.; Findings: Endotoxin levels varied geographically, with the highest averages in Italy and the lowest in Finland. After adjusting for confounders, exposure to endotoxin levels at or above the median was associated with higher odds of upper and lower respiratory symptoms—runny nose, nasal obstruction, cough, dry throat, breathing difficulty, and feverishness—as well as reduced lung function (p < 0.05). Meta-analysis by WHO European clusters confirmed these associations, though region-specific analyses indicated a possible protective effect of endotoxin exposure in Northern Europe.; Interpretation: Findings from SINPHONIE highlight classroom endotoxin as a potential environmental determinant of respiratory health. Reducing exposure in schools—currently an overlooked setting—may support respiratory well-being in children and inform future public health policies.