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.

Influence of inhalation device, active substance, and drug formulation on the compliance of patients with obstructive pulmonary diseases. A physicians... perspective.

AIM: To investigate the perspective of physicians treating chronic airway diseases on the importance of device and substance characteristics influencing the compliance of patients with chronic obstructive airways diseases. OBJECTIVE: We surveyed physicians... perspective on the impact of device and substance characteristics on patients... compliance. METHODS: This study was carried out by running a structured questionnaire, to a total of 144 physicians, conducting personal interviews and evaluating answers on a scale from 1 for most to 6 for least important influencing parameter. RESULTS: Overall, the most important parameters influencing patients... compliance according to physicians... perspective were rapid onset of action, type of inhalation device and duration of action. Adverse events were considered as the least important parameter. When COPD and asthma were examined separately, the most important parameters influencing compliance were rapid onset of action, ease of use and duration of action. Rapid onset of action was significantly more important in asthma than COPD. CONCLUSION: Onset and duration of action and ease of use were classified higher as important parameters to increase patients... compliance, according to physicians...

Differential immunohistochemical expression of hTERT in lung cancer patients with and without idiopathic pulmonary fibrosis.

BACKGROUND: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase enzyme, which adds nucleotides to telomeres and counteracts their length shortening. The development of a telomere maintenance mechanism represents a hallmark of cancer. On the other hand, idiopathic pulmonary fibrosis (IPF) is associated with mutations in telomerase genes and shorter telomeres. IPF is frequently complicated with lung cancer. AIM: To investigate the expression of hTERT in lung cancer with co-existing IPF and to compare with lung cancer without fibrosis. METHODS: Diagnostic lung cancerous biopsies were retrieved from 18 patients with lung cancer and concomitant IPF, as well as 18 age and gender matched controls with lung cancer without pulmonary fibrosis. The expression of hTERT was studied with immunohistochemistry. ImajeJ software was used to quantitate subcellular stain intensity. Immunohistochemical investigation of two senescence-associated markers, p16 and p21, was also performed in all 36 cases. RESULTS: Both groups highly expressed hTERT, without significant difference (100% vs 95%, p = 0.521). Evaluation of p16 and p21 immunostaining revealed negative to minimal immunoreactivity in both groups. hTERT localization exhibited higher median nuclear intensity in the group of lung cancer with IPF (0.62 vs 0.45, p = 0.016), while cytoplasmic intensity did not differ significantly (0.17 vs 0.15, p = 0.463). Higher median nuclear intensity was also correlated with small cell lung cancer subtype in the whole study sample (0.69 vs 0.45, p = 0.09). CONCLUSION: hTERT is highly expressed in lung cancer with concomitant IPF, but with differential localization compared to lung cancer without IPF, implying differences in pathogenicity and requiring further investigation.

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.

γ -H2AX: A Novel Prognostic Marker in a Prognosis Prediction Model of Patients with Early Operable Non-Small Cell Lung Cancer.

Cancer is a leading cause of death worldwide and the prognostic evaluation of cancer patients is of great importance in medical care. The use of artificial neural networks in prediction problems is well established in human medical literature. The aim of the current study was to assess the prognostic value of a series of clinical and molecular variables with the addition of γ -H2AX-a new DNA damage response marker-for the prediction of prognosis in patients with early operable non-small cell lung cancer by comparing the γ -H2AX-based artificial network prediction model with the corresponding LR one. Two prognostic models of 96 patients with 27 input variables were constructed by using the parameter-increasing method in order to compare the predictive accuracy of neural network and logistic regression models. The quality of the models was evaluated by an independent validation data set of 11 patients. Neural networks outperformed logistic regression in predicting the patient's outcome according to the experimental results. To assess the importance of the two factors p53 and γ -H2AX, models without these two variables were also constructed. JR and accuracy of these models were lower than those of the models using all input variables, suggesting that these biological markers are very important for optimal performance of the models. This study indicates that neural networks may represent a potentially more useful decision support tool than conventional statistical methods for predicting the outcome of patients with non-small cell lung cancer and that some molecular markers, such as γ -H2AX, enhance their predictive ability.

H2AX a promising biomarker for lung cancer: a review.

Histone's H2A variant (H2AX) phosphorylation is an early indicator of DNA double-strand breaks formation and DNA damage response. Thus, it may act as a novel biomarker to monitor genotoxic events that can drive cancer development and tumor progression. This review will focus on the possible applications of H2AX as a key regulator of DNA damage response in lung cancer and as a biomarker of: sensitivity of lung tumors to chemotherapy and radiotherapy, treatment with PARP inhibitors, bystander effect, multistep lung carcinogenesis, environmental smoking, and chemical genotoxicity, chemoprevention, prognosis, and also as therapeutic targets in lung cancers.

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.

Mean platelet volume and platelet distribution width in patients with chronic obstructive pulmonary disease: the role of comorbidities.

We evaluated mean platelet volume (MPV; an indicator of vascular risk) and platelet distribution width in patients with stable chronic obstructive pulmonary disease (COPD; n = 85). We also included a control group of 34 smokers without airflow limitation. Mean platelet volume was significantly higher in patients with COPD (10.69 ± 1.0 vs 9.96 ± 1.10 fL, P < .001) than in the smoker controls. White blood cell (WBC) count was also significantly higher in patients with COPD than in the smoker controls (10,642 ± 1247 vs 7136 ± 1887/µL, P < .001). There was a correlation between MPV and WBC in patients with COPD, especially in those at stage III (r = .530, P = .004) and IV (r = .389, P = .023). Mean platelet volume did not correlate with any indices of COPD severity. In patients with COPD, MPV and WBC levels are higher than those of smokers with normal pulmonary function and are significantly correlated. Whether these effects relate to vascular risk in patients with COPD remain to be established.

Mean Platelet Volume and Platelet Distribution Width in non-diabetic subjects with obstructive sleep apnoea syndrome: new indices of severity?

UNLABELLED: To evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in non-diabetic subjects, according to obstructive sleep apnoea syndrome (OSAS) severity and the associations of these indices with anthropometric characteristics and parameters of breathing function during sleep. MATERIALS AND METHODS: We included 610 non-diabetic subjects with suspected OSAS, evaluated by polysomnography. According to their apnoea-hypopnoea index (AHI), patients were divided into Group A (n=148) with AHI<5/h; Group B (n=121) with AHI: 5-14.9/h; Group C (n=85) with AHI: 15-29.9/h and Group D (n=256) with AHI ≥ 30/h. MPV and PDW were measured using an automated blood cell counter. RESULTS: MPV was significantly higher in group D (mean value 12.1 ± 1.3 fl) than in groups A (9.8 ± 1.1 fl), B (9.8 ± 1.6 fl), and C (11.5 ± 1.3 fl) (p<0.001). The same pattern was observed in PDW values (15.9 ± 2.2 fl for group D and 13.2 ± 2.2 fl for group A, 14.1 ± 2.8 fl for group B, and 15 ± 2.2 fl for group C, p<0.001). Significant correlations were seen between MPV and AHI (p<0.001), average pulse oxygen saturation (SpO(2)) (p<0.001), minimum SpO(2) (p<0.001) and percent of the total sleep time with SpO(2) lower than 90% (t<90%) (p<0.001) during sleep, Arousal Index (p<0.001) and Epworth sleepiness scale (ESS) (p=0.028). Similarly, PDW was correlated with AHI (p<0.001), average SpO(2) (p=0.001), minimum SpO(2) (p<0.001), t<90% (p=0.002), and Arousal Index (p<0.001). CONCLUSIONS: MPV and PDW are higher in non-diabetic patients with severe OSAS and are correlated with different parameters of breathing function during sleep.

Clinical patterns and treatment outcome in resected elderly lung cancer patients.

PURPOSE: Lung cancer is the leading cause of cancer related morbidity and mortality worldwide. The aim of this study was to determine the clinical patterns and their impact on surgical resection in patients with non-small cell lung cancer (NSCLC)> 70 years. METHODS: We reviewed the records of 2050 resected lung cancer patients in a 5-year period from 2002-2007, out of whom 93 were > 70 years. RESULTS: There were 73 males and 20 females with median age of 71 years (range 70-78). Nineteen (20.43%) patients underwent pneumonectomy, 6 (6.45%) extended pneumonectomy, 54 (58.06%) lobectomy, 8 (8.61%) extended lobectomy, and 3 (3.23%) bilobectomy and wedge resection each. There were 37 (39.8%) resected patients with locally advanced (IIIA, IIIB) or advanced stage (IV) of NSCLC. A total of 48 complications occurred. The 30-day mortality rate was 1.08% (one patient). Pathological stage (p<0.001) and application of adjuvant therapy (p<0.001) were predictors of long-term survival. The overall 3- and 5-year actuarial survival rates were 46% and 28%, respectively. CONCLUSION: Advanced age should not be considered as a contraindication for NSCLC resection. However, careful preoperative assessment must be undertaken. The presence of comorbidities and extent of resection predict increased operative risk. Pathological stage and application of adjuvant therapy were the only predictors of long-term survival.

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.

Changes in tuberculin sensitivity among first-grade students of elementary schools in Evros, Greece due to immigration.

OBJECTIVE: To investigate the tuberculin sensitivity trends among first-grade students of elementary schools tested according to the Greek national school-based screening and vaccination programme. STUDY DESIGN: Retrospective analysis of tuberculin skin test (TST) results from 1988 to 2004 in unvaccinated first-grade students in Evros, Greece. METHODS: All 6-7-year-old children who were unvaccinated for tuberculosis were tested by a highly experienced team. This study tested whether gender (male vs female), national origin (native vs foreign-born children) and place of residence (urban vs semi-urban vs rural) correlated with tuberculin reaction positivity. RESULTS: In total, 8588 children (47.1% girls) were tested. Tuberculin reaction positivity was independent of gender. The difference in TST positivity between native and foreign-born children between 1993 and 2004 was highly significant, with substantially more foreign-born children having a positive Mantoux test (P<0.0001). The percentage of children with a positive TST peaked at 13% in 1995 due to initial admission of foreign-born children, originating from countries of the former Soviet Union, into the Greek educational system. In addition, a positive Mantoux test was more common among children living in rural (8.1%) and semi-urban (6.4%) areas compared with children living in urban areas (3.5%, P<0.0001). CONCLUSION: The increase in TST positivity noted was due to admission of foreign-born children into the Greek educational system. School-based tuberculosis screening programmes should continue in Greece because the prevalence of tuberculosis appears to show substantial variation between years.