Genotype-Phenotype Relationships in Inheritable Idiopathic Pulmonary Fibrosis: A Greek National Cohort Study.

BACKGROUND: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients' characteristics in the Greek national IPF cohort with suspected heritability. PATIENTS AND METHODS: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. RESULTS: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. CONCLUSION: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease's genetic "richesse," complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating "personalized" medical care driven by genotypes in the near future.

False Positive COVID-19 Antibody Test in a Case of Granulomatosis With Polyangiitis.

Collateral damage due to 2019 novel coronavirus disease (COVID-19) represents an emerging issue. Symptoms of COVID-19 are not disease-specific. Differential diagnosis is challenging and the exclusion of other life-threatening diseases has major caveats. In the era of this pandemic, diagnosis of other life-threatening diseases might delay treatment. The Food and Drug Administration has recently authorized the first antibody-based test for COVID-19; however, RT-PCR of nasopharyngeal or oropharyngeal swabs remains the recommended test for diagnosis. We present the first report of a false positive COVID-19 antibody test in a case of Granulomatosis with Polyangiitis (GPA). Specifically, the case concerns an 82-year-old female, never smoker, who was admitted to our hospital with symptoms of fever and general fatigue that had lasted 7 days. She already had a positive IgM test for COVID-19, yet multiple RT-PCR tests had returned as negative for SARS-CoV-2. In the following days, her renal function deteriorated, while hematuria and proteinuria with active urinary sediment developed. Based on high clinical suspicion for ANCA-associated vasculitis, we performed a complete immunologic profile which revealed positive c-ANCA with elevated titers of anti-PR3. Pulses of methylprednisolone along with cyclophosphamide were applied. At day 10, treatment response was noticed as indicated by respiratory and renal function improvement. This report highlights the need for meticulous patient evaluation in order to avoid misdiagnosis in the era of COVID-19.

Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece.

BACKGROUND: Pirfenidone is an antifibrotic compound able to slow down disease progression in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To investigate the safety and efficacy of pirfenidone in patients with IPF in a real-life setting. METHODS: This was a multicenter, retrospective, real-life, observational study for patients with IPF receiving pirfenidone. RESULTS: We identified 92 patients with IPF receiving pirfenidone. Eighty patients (70 males and 10 females, mean age ± SD: 68.1 + 7.5, mean %FVC ± SD = 74.9 ± 17.2, mean %DLCO ± SD = 48.1 ± 16.9) were included in the analysis. Skin-related (25%) and gastrointestinal (17.5%) adverse events were the most common and led to drug discontinuation in 22.5% of cases. The majority (87%) of patients experienced side effects during the first 6 months of treatment. At 36 months, changes in %FVC and %DLCO were -9.25 ± 16.34 and -9.26 ± 15.26, respectively. At 6, 12, and 24 months after treatment initiation (n = 80, 60, and 26), 18, 15, and 5 patients (22.5, 25, and 19.2%) experienced significant (>10%) and 11, 3, and 3 patients (13.8, 5, and 11.5%) experienced marginal (5-10%) %FVC improvement; and 13, 6, and 1 patient (16.2, 10, and 3.9%) experienced marginal (-5 to -10%) and 20, 21, and 8 patients (25, 35, and 30.8%) experienced significant decline (<-10%) in %FVCpred. Median survival was 851 days, and 41 patients died during the study period. CONCLUSION: Pirfenidone demonstrated an acceptable safety and therapeutic profile in patients with IPF on a longitudinal basis. Prospective observational registries are urgently needed to provide a real-world view of outcomes of pirfenidone in clinical practice.

Corrigendum: Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece.

[This corrects the article on p. 213 in vol. 4, PMID: 29238708.].

Prolonged occupational exposure leads to allergic airway sensitization and chronic airway and systemic inflammation in professional firefighters.

BACKGROUND AND OBJECTIVES: Little data exist on short- and long-term effects of occupational exposure on airway and systemic inflammation in professional firefighters. We aimed to characterize airway and systemic inflammation in training firefighters with a maximum occupational exposure of 1 year compared to the long-term exposure of professional firefighters. METHODS: A questionnaire for symptoms and exposure, pulmonary function, atopy, bronchial hyper-responsiveness, and markers of inflammation in induced sputum, serum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies were assessed in a total of 92 firefighters (63 full-time professionals and 29 trainees). RESULTS: Professional firefighters showed allergic bronchial sensitization documented by the presence of atopy, and eosinophilia in induced sputum, BAL and bronchial biopsies. IL-8, ECP, VEGF, and TNF-α levels were statistically significantly higher in the sputum supernatants of professional firefighters compared to the trainees (p = 0.04, p = 0.02, p = 0.04, and p = 0.02, respectively). Serum IL-8 and TNF-α levels were also statistically significantly higher in the group of professional firefighters (p = 0.04, p = 0.03, respectively). Finally, there was a linear correlation between the duration of the occupation in Service and the degree of airway and systemic inflammation. CONCLUSIONS: These results indicate a "dose-response" effect of chronic exposure to a polluted environment on bronchial and systemic inflammation in professional firefighters.

Calprotectin: a protein related to cardiovascular risk in adult patients with obstructive sleep apnea.

INTRODUCTION: Increased levels of inflammatory mediators, such as hs-CRP, have been detected in patients with obstructive sleep apnea (OSA) and used as cardiovascular risk and disease outcome predictors. Calprotectin is an inflammatory marker regulating atherogenic processes not investigated in adult OSA patients. The aim of the present study as primary objective was to examine the role of calprotectin as an inflammatory molecule, acting through a distinct pathway to the atherogenic process in adult OSA patients and its associations with hs-CRP and the lipidemic profile of the patients. As a secondary objective was the evaluation of the atherogenic markers post-CPAP treatment. MATERIALS AND METHODS: Seventy-four participants underwent full overnight polysomnography. Blood samples were collected for calprotectin, hs-CRP, total cholesterol, triglycerides, LDL, HDL and glucose levels. Thirty-two OSA patients were reexamined 6 months post-CPAP treatment. RESULTS: Out of 74 participants included in the study, 33 had moderate OSA, 27 had severe OSA and 14 were controls. Calprotectin and hs-CRP were significantly increased in patients with moderate and severe OSA compared to controls (p<0.0001). Calprotectin and hs-CRP levels were positively correlated with apnea-hypopnea index, BMI and total time of sleep with SaO(2)<90% and inversely correlated with SaO(2) minimum and mean values. Calprotectin and hs-CRP levels were significantly improved post-CPAP treatment (p<0.0001). DISCUSSION: Calprotectin may serve as a novel and reliable, biomarker of cardiovascular risk severity in OSA patients. The decrease of calprotectin levels post-CPAP treatment combined with hs-CRP amelioration could provide evidence for reduction of cardiovascular risk post CPAP treatment.