RESUMO
BACKGROUND: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers. METHODS: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers. RESULTS: We identified 99 SRG adult variant carriers (SFTPA1 (n=18), SFTPA2 (n=31), SFTPC (n=24), ABCA3 (n=14) and NKX2-1 (n=12)), including 20 (20.2%) with lung cancer (SFTPA1 (n=7), SFTPA2 (n=8), SFTPC (n=3), NKX2-1 (n=2) and ABCA3 (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01-1.08), smoking (OR 20.7, 95% CI 6.60-76.2) and SFTPA1/SFTPA2 variants (OR 3.97, 95% CI 1.39-13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24â months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 (95% CI 7.1-44.7). CONCLUSIONS: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated.
Assuntos
Neoplasias Pulmonares , Proteína A Associada a Surfactante Pulmonar , Proteína C Associada a Surfactante Pulmonar , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Proteína C Associada a Surfactante Pulmonar/genética , Proteína A Associada a Surfactante Pulmonar/genética , Adulto , Fator Nuclear 1 de Tireoide/genética , Transportadores de Cassetes de Ligação de ATP/genética , Fatores de Risco , Predisposição Genética para Doença , Doenças Pulmonares Intersticiais/genética , Heterozigoto , Proteínas Associadas a Surfactantes Pulmonares/genéticaRESUMO
Coronavirus disease 2019 (COVID-19) may be complicated by life-threatening pneumonia requiring tracheal intubation, mechanical ventilation and veno-venous extracorporeal membrane oxygenation (vvECMO). It is not yet clear to what extent and after which delay the most severe cases of COVID-19 pneumonia are reversible. Here, we present a 39-year-old patient who developed a severe COVID-19-attributed acute respiratory distress syndrome (ARDS) resulting in complete alveolar consolidation and airway closure for several weeks. His remarkable ventilatory pattern was established using ventilator airway pressure curve analysis and computed tomography imaging. The patient was managed with supportive care, mechanical ventilation and vvECMO. He received dexamethasone and tocilizumab as immunomodulatory drugs. Despite multiple complications, he recovered and was weaned from vvECMO, ventilator and oxygen on days 75, 95 and 99 post-intubation, respectively. He was discharged from hospital on day 113. This case study strongly supports the remarkable potential for reversibility of ARDS in COVID-19 patients and discusses the implications for critical care nursing regarding mechanical ventilation and ECMO device management in patients who may become entirely dependent on vvECMO for oxygenation and carbon dioxide elimination.