Elevated peripheral blood monocyte count is associated with prolonged postoperative hospitalization and functional decline in patients with interstitial lung diseases undergoing surgical lung biopsy.

OBJECTIVE: Monocyte count and red cell distribution width (RDW) have shown prognostic potential in patients with fibrotic lung diseases. Their kinetics and prognostic usefulness of peripheral blood indices in patients with interstitial lung diseases (ILDs) undergoing surgical lung biopsy for diagnostic reasons have not been studied. PATIENTS AND METHODS: We retrospectively included consecutive patients with ILD who underwent surgical lung biopsy for diagnostic purposes Between 07/11/2019 and 11/10/2022. RESULTS: Fifty-five (n=55) patients were included in the study. Median age was 65.0 years (95% CI: 63.0 to 66.0). Postoperative peripheral blood monocyte count on Day 1 was significantly higher compared to preoperative, perioperative, and postoperative values on Day 90 (repeated measures ANOVA, p<0.0001). Patients in the high postoperative monocyte count group had significantly increased length of postoperative hospital stay [Mann-Whitney test, p=0.007] and significantly lower Forced Vital Capacity (FVC)% predicted 3 months after surgery [Mann-Whitney test, p=0.029] compared to patients in the low postoperative monocyte count group. Postoperative RDW on Day 90 was significantly higher compared to preoperative, perioperative and postoperative-Day 1 RDW (repeated measures ANOVA, p=0.008, p=0.006, p<0.0001, respectively). Patients in the high postoperative RDW group did not have increased hospital stay (Mann-Whitney test, p=0.49) or decreased FVC% predicted at 3 months compared to patients in the low postoperative RDW group (Mann-Whitney test, p=0.91). CONCLUSIONS: Peripheral blood monocyte count could be a prognostic biomarker for patients with ILDs undergoing diagnostic surgical lung biopsies. RDW does not seem to represent an acute phase biomarker but seems to increase over time following disease progression. Larger studies are urgently required.

Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Clinical outcomes in vaccinated and unvaccinated patients with COVID-19: a population-based analysis.

OBJECTIVE: Real-life data for vaccination against COVID-19 are sorely needed. This was a population-based analysis aiming at investigating the hospitalization risk for COVID-19 of 98,982 subjects and compare features of vaccinated and unvaccinated patients. PATIENTS AND METHODS: Hospitalized patients with COVID-19 between 01/07/2021 and 11/02/2022 were included in the study. RESULTS: 582 patients were included in the analysis [males: 58.6% (n=341), vaccinated patients: 28.5% (n=166), unvaccinated patients: 71.5% (n=416)]. Median age of vaccinated patients was significantly higher compared to median age of unvaccinated [74.0 (95% CI: 72.0-77.0) vs. 59.0 (95% CI: 57.0-62.0), p=0.0001]. Mean latency time (±SD) from the second dose to hospitalization was 5.7±2.6 months. Between 01/07/2021 and 01/12/2021, unvaccinated subjects had higher risk for hospitalization compared to vaccinated [HR: 2.82, 95% CI: 2.30-3.45, p<0.0001]. Between 02/12/2021 and 11/02/2022, unvaccinated subjects presented with higher risk for hospitalization than subjects that had received booster dose [HR: 2.07, 95% CI: 1.44-2.98, p=0.005], but not than subjects that got two doses. Median value of hospitalization days was higher in unvaccinated patients compared to vaccinated [7.0 (95% CI: 7.0-8.0) vs. 6.0 (95% CI: 5.0-7.0), p=0.02]. Finally, age-adjusted analysis showed that hospitalized unvaccinated patients presented with significantly higher mortality risk compared to hospitalized vaccinated patients [HR: 2.59, 95% CI: 1.69-3.98, p<0.0001]. CONCLUSIONS: Vaccination against COVID-19 remains the best way to contain the pandemic. There is an amenable need for booster dose during the omicron era.

CTPA imaging findings, beyond pulmonary embolism, in patients with Severe Acute Respiratory Syndrome Corona Virus-2 infection and their relation to clinical outcome - a single center experience.

OBJECTIVE: The aim of our study was to investigate a potential association between the severity of COVID-19 disease and related 28-day mortality, with the presence of mediastinal lymphadenopathy, the extension of lung parenchymal infiltrates, the presence of pulmonary embolism, the density and distribution of mediastinal and subcutaneous fat, the inflammatory markers and the direct and indirect radiological signs of right heart overload and strain. PATIENTS AND METHODS: We retrospectively included patients diagnosed with SARS-CoV-2 infection, who were admitted to the Departments of Internal and Respiratory Medicine of Patras University Hospital during the second pandemic wave (February 2021 up to July 2021) and underwent CTPA for routine diagnostic workup. Demographic characteristics, routine laboratory, radiological parameters and 28-day mortality were also recorded. RESULTS: Fifty-three consecutive patients were included. The mean age was 64.47±17.1 years and 64,1% (n=34) were males. Pulmonary embolism (PE) (p=0.019), Right Ventricle-to-Left Ventricle Diameter (RV/LV)  Ratio>1 (p<0.01), Reverse Flow in Hepatic Veins (RFHV) (p=0.019), higher density in subcutaneous fat (-99 HU vs. -104HU, p=0.016), increased Lactic Dehydrogenase (LDH), Polymorphonuclear cells (PMN), ferritin, and d-dimer levels (534 vs. 367 U/L, p=0.001, 9220 vs. 5660 Κ/µL, p=001, 956 vs. 360 ng/ml, p=0.005 and 2300 vs. 1040 µg/ml, p=0.003, respectively) were statistically significant related with worse 28-day mortality. Binomial multivariate regression analysis revealed that only RV/LV diameter>1, higher subcutaneous fat density and higher LDH values were independently associated with increased 28-day mortality (OR: 82.9, 95%CI: 1.334-5158, p=0.036, OR: 1.2, 95%CI: 1.016-1.426, p=0.032 and OR:1.016, 95% CI:1.004-1.029, p=0.011, respectively). Subgroup analysis revealed that mediastinal lymph node enlargement (EML) and PE were associated to increased Pulmonary Disease Severity Index (PDSI) score (p=0.042 and p=0.007, respectively), but not to mortality. CONCLUSIONS: Our study showed that right heart strain as depicted by a RV/LV diameter>1, higher subcutaneous fat density and higher LDH values are independently associated with an increased 28-day mortality in our SARS-COV2 patient group.

Prevalence and significance of mediastinal lymphadenopathy in patients with Severe Acute Respiratory Syndrome Corona Virus-2 infection.

Severe Acute Respiratory Syndrome Corona Virus-2 is the causative factor of Coronavirus Disease 2019. Early in the pandemic, mediastinal lymphadenopathy was not considered to be a significant radiologic finding of the SARS-COV-2 disease. Nevertheless, most recent studies associate mediastinal lymphadenopathy with more severe COVID-19 disease and poorer patient outcomes.

Insulin Sensitivity and Insulin Resistance in Non-Diabetic Middle-Aged Patients with Obstructive Sleep Apnoea Syndrome.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) has been linked with abnormal glucose metabolism, insulin resistance (IR) and development of diabetes mellitus. METHODS: Non-diabetic patients (n=69) with OSAS, diagnosed by polysomnography, were prospectively recruited. To evaluate IR among OSAS patients, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Insulin sensitivity by Quantitative Insulin sensitivity Check Index (QUICKI) were used. RESULTS: HOMA-IR was positively associated with body-mass index (BMI) (ρ=0.364, p=0.002), time with oxyhaemoglobin saturation <90% (ρ=0.291, p=0.015), arousal index (ρ=0.268, p=0.027), Epworth sleepiness scale (ESS) score (ρ=0.293, p=0.019) and negatively with average oxyhaemoglobin saturation (ρ=-0.398, p=0.001) and minimum oxyhaemoglobin saturation (ρ=-0.327, p=0.006). QUICKI was positively associated with forced vital capacity (r=0.301, p=0.014), average oxyhaemoglobin saturation (r=0.443, p<0.001), minimum oxyhaemoglobin saturation (ρ=0.318, p=0.008), and negatively associated with sleep stage transitions (r=-0.266, p=0.032), oxygen desaturation index (r=-0.404, p=0.005), time with oxyhaemoglobin saturation <90% (r=-0.311, p=0.019), arousal index (r=-0.344, p=0.004) and ESS score (r=-0.299, p=0.016). After adjustment for age and BMI, HOMA-IR was associated with sleep stage transitions, time with oxyhaemoglobin saturation <90%, average oxyhaemoglobin saturation, minimum oxyhaemoglobin saturation and arousal index. QUICKI was associated with oxygen desaturation index, sleep stage transitions, ESS score, minimum oxyhaemoglobin saturation and arousal index. CONCLUSIONS: An independent association between OSAS and IR in patients without pre-existing diabetes mellitus was observed. Recurrent hypoxia and sleep fragmentation in OSAS are associated with IR in these patients.

Mean Platelet Volume as a Surrogate Marker for Platelet Activation in Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a prothrombotic state. AIM: To study mean platelet volume (MPV) and Platelet Distribution Width (PDW) as markers of platelet activation and their potential association with lung function in patients with recently diagnosed IPF. MATERIALS AND METHODS: This study included 56 patients with IPF (age 64.9±7.4 years) and 79 controls (age 64.2 ± 5.9 years). RESULTS: An inverse relation was demonstrated between platelet count and MPV in the control group but not among patients with IPF. Platelet count was significantly lower in patients with IPF compared with controls (230 ± 60 vs 256 ± 75 × 10(3)/µL, P = .038). Conversely, MPV was higher in patients versus controls (10.3 ± 1.2 vs 9.8 ± 1.2 fl, P = .024), while there was no difference between the groups in PDW. Respiratory function was, as expected, significantly impaired in patients with IPF versus controls in terms of forced expiratory volume in first second (FEV1; 67.2 ± 23.1 vs 102.6 ± 15.9% of predicted value, P < .001), forced vital capacity (FVC; 65.3 ± 21 vs 95.2 ± 16.1% of predicted value, P < .001), FEV1/FVC (83.1 ± 15 vs 87.5 ± 6.4%, P = .041) and partial pressure of oxygen in arterial blood (PaO2; 67.1 ± 10.3 vs 81.5 ± 15.2 mm Hg, P < .001). No significant correlation was seen between MPV and FVC (r = -.1497, P = .275), MPV and lung diffusion capacity for carbon monoxide (r = .035, P = .798) and total lung capacity (r = .032, P = .820). CONCLUSIONS: Patients with IPF exhibit higher MPV values and lower platelet count. Further studies are needed to assess the clinical implications of these findings.

Is there evidence of early vascular disease in patients with obstructive sleep apnoea without known comorbidities? Preliminary findings.

We evaluated early atherosclerotic lesions in 20 non-smokers with newly diagnosed Obstructive Sleep Apnoea (OSA) and without known comorbidities by measuring common carotid artery intima media thickness (CCA-IMT), transcranial Doppler ultrasound (TCD), and ankle brachial index (ABI). These were compared with 20 healthy age- and BMI-matched controls. In OSA patients, CCA-IMT was not significantly higher vs. controls (0.74±0.17 vs. 0.66±0.12 mm, p=0.201) and it was positively correlated with neck circumference (r=0.466, p=0.039), arousal index (r=0.663, p=0.001), gamma-glutamyl transpeptidase activity (r=0.474, p=0.035) while it was negatively correlated with Forced Expiratory Volume in 1 sec (r=-0.055, p=0.012). No difference was noted between patients and controls in terms of vascular stenosis on TCD examination, while asymptomatic peripheral artery disease was found in one patient with OSA. In conclusion, OSA patients without known comorbidities exhibit a non-significant increase in CCA-IMT without further evidence of vascular disease, but additional experience in a larger patient series is needed.

Unilateral pulmonary artery agenesis: a case series.

BACKGROUND: Unilateral pulmonary artery agenesis (UPAA) is a rare congenital anomaly due to a malformation of the sixth aortic arch of the affected side during embryogenesis. The diagnosis is usually set at adolescence, however it can remain asymptomatic and late diagnosis is possible. DESCRIPTION: We present a case series of three female patients, aged 18, 49 and 68 years old, with history of recurrent respiratory tract infections, to whom the diagnosis of UPAA was set. They were admitted, due to hemoptysis and productive cough (case 1) or progressive dyspnea on exertion (cases 2 and 3). Chest X-ray was abnormal in all three cases, depicting shift of the mediastinal structures to the left and hypoplasia of the left lung while chest CT demonstrated absence of the left pulmonary artery. CONCLUSION: UPAA can remain asymptomatic and diagnosis in adult age is possible, usually after an abnormal chest radiograph. A number of additional imaging techniques are available to aid the diagnosis. Physicians should consider the possibility of undiagnosed UPAA in adults.

Prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis: correlation with physiological parameters.

The aim of this study was to prospectively evaluate the prevalence of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF). One hundred thirty-nine patients (101 male, mean age = 68.6 ± 9 years), with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study. Pulmonary artery systolic pressure (PASP) was estimated by echocardiography, and PH was defined as PASP > 36 mmHg. We compared demographics, pulmonary function tests, NYHA functional status, 6-min walk distance (6MWD), B-type natriuretic peptide (BNP), PaO(2), and P(A-a)O(2) at rest data between patients with PH and without PH (PASP ≤ 36 mmHg). Increased estimated right ventricular systolic pressure was present in 55% of patients (mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg, respectively). Patients with PH had a lower but not statistically significant DL(CO) (47.1 ± 18.8 vs. 52.5 ± 20.1), lower PaO(2) at rest (64.6 ± 12.2 vs. 71.1 ± 11.3, P = 0.004), and lower mean 6MWD (282 ± 118 vs. 338 ± 91, P = 0.007). Significant differences were also observed in the NYHA functional status between the two groups (P = 0.02). Statistically significant correlations were observed between PASP and PaO(2) at rest (r = -0.331, P = 0.00), P(A-a)O(2) at rest (r = 0.494, P = 0.00)(,) 6MWD (r = -0.264, P = 0.01), SpO(2) at rest (r = -0.293, P = 0.00), SpO(2) at the end of exercise (r = -0.364, P = 0.00), and also BNP values (r = 0.319, P = 0.01). Moreover, PaO(2) (P = 0.02), P(A-a)O(2) (P = 0.005), and SpO(2) at the end of exercise (P = 0.023) were independent predictors of the presence of estimated PH. Using Doppler echocardiography as a screening tool for the estimation of PH, we found that PH is common in patients with IPF. Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF.

Gelsolin expression is necessary for the development of modelled pulmonary inflammation and fibrosis.

BACKGROUND: Despite intense research efforts, the aetiology and pathogenesis of idiopathic pulmonary fibrosis remain poorly understood. Gelsolin, an actin-binding protein that modulates cytoskeletal dynamics, was recently highlighted as a likely disease modifier through comparative expression profiling and target prioritisation. METHODS: To decipher the possible role of gelsolin in pulmonary inflammation and fibrosis, immunocytochemistry on tissue microarrays of human patient samples was performed followed by computerised image analysis. The results were validated in the bleomycin-induced animal model of pulmonary inflammation and fibrosis using genetically-modified mice lacking gelsolin expression. Moreover, to gain mechanistic insights into the mode of gelsolin activity, a series of biochemical analyses was performed ex vivo in mouse embryonic fibroblasts. RESULTS: Increased gelsolin expression was detected in lung samples of patients with idiopathic interstitial pneumonia as well as in modelled pulmonary inflammation and fibrosis. Genetic ablation of gelsolin protected mice from the development of modelled pulmonary inflammation and fibrosis attributed to attenuated epithelial apoptosis. CONCLUSIONS: Gelsolin expression is necessary for the development of modelled pulmonary inflammation and fibrosis, while the caspase-3-mediated gelsolin fragmentation was shown to be an apoptotic effector mechanism in disease pathogenesis and a marker of lung injury.

Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis.

Sarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two independent studies have recently shown that a functional polymorphism within butyrophilin-like 2 (BTNL2) gene predisposes to sarcoidosis independently of the human leukocyte antigen (HLA)-DRB1 alleles. However, in both studies, data analysis was not stratified by Löfgren's syndrome, a clinically and genetically distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is adjacent and in linkage disequilibrium (LD) with HLA-DRB1. We investigated six BTNL2 variants, including the functional rs2076530 (G > A), as well as HLA-DRB1 alleles, by sequence-specific primers-polymerase chain reaction, in 288 patients and 446 controls from two European countries. In the patient group as a whole, the HLA-DRB1*14 [odds ratio (OR) = 3.1, P(c) = 0.0003], DRB1*12 (OR = 2.5, P(c) = 0.003), and BTNL2 rs2076530 A allele (OR = 1.49, P(c) = 0.002) were all associated with disease susceptibility. However, after exclusion of patients presenting with Löfgren's syndrome and after adjusting for HLA-DRB1 alleles, the association between BTNL2 rs2076530 A and disease disappeared (P = 0.23). By contrast, both HLA-DRB1*14 and DRB1*12 remained strongly significant (OR = 3.60, P < 0.0001 and OR = 3.03, P = 0.003, respectively). BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non-Löfgren sarcoidosis after adjusting for HLA-DRB1 alleles (OR 0.37, P = 0.016). In summary, HLA-DRB1*14, DRB1*12, and BTNL2 haplotype 4--but not rs2076530 A--are associated with non-Löfgren sarcoidosis. However, the tight LD across the HLA complex makes it difficult to identify the precise location of the susceptibility locus/i. Larger sample sets from different ethnic groups, finer mapping, and more robust LD analyses across the HLA region are needed.