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.

The "reversed halo" sign in pneumonococcal pneumonia: a review with a case report.

The "reversed halo" sign (RHS) is a distinct radiological sign representing a focal rounded area of ground-glass opacity surrounded by a more or less complete ring of consolidation. Initially, it was reported in two cases of cryptogenic organizing pneumonia and was considered to be relatively specific of the disease. Since then, it has been reported in a wide variety of clinical entities, thus reducing its specificity. We describe the reversed halo sign in a case of pneumonococcal pneumonia. To the best of our knowledge, this is the first report in English literature. The presence of the "reversed halo" sign during the resolution phase of pneumonococcal pneumonia has serious implications. First, it further reduces its specificity. Second, it opens new areas of research regarding its significance in cases of cryptogenic organizing pneumonia.

A rare cause of dysphagia--aberrant right subclavian artery (ARSA).

Aberrant Right Subclavian Artery (ARSA) is a rare vascular anomaly. It is though the most frequent anomaly involving the aortic arch, being present in about 1% of the general population. We present a case of a 71 year old male with symptoms of chronic cough and dysphagia. He was referred to our clinic for further evaluation of a mediastinal mass. A second Computed Tomography of the thorax was performed, this time with the use of i.v. contrast. The latter examination confirmed the diagnosis (ARSA), sparing the patient of invasive and potentially life threatening diagnostic procedures (invasive angiography, mediastinoscopy). This case highlights the significant pitfalls regarding the mediastinal evaluation, especially when i.v. contrast is not used. The majority of the mediastinal structures are vessels. Vessels abnormalities should be included in the differential diagnosis of a mediastinal mass.

A 77 year old male with peripheral eosinophilia, pulmonary infiltrates and a small pleural effusion.

The presence of peripheral eosinophilia with lung infiltrates poses a diagnostic challenge for the clinician. The differential diagnosis includes a wide spectrum of diseases. In some of them (for example vasculitis, lymphoma) eosinophilic pneumonia represents just another "symptom" and not the final diagnosis. A thorough diagnostic procedure is required to examine all related clinical entities in order to establish a firm diagnosis. In particular, Idiopathic Chronic Eosinophilic Pneumonia (ICEP) is a rare disorder. In the majority of cases, it is characterized by peripheral eosinophilia, lung infiltrates, bronchoalveolar lavage eosinophilia (above 25%), exclusion of other possible causes and last but not least an impressive improvement under steroid therapy. Relapses are common but they do not seem to be related with ICEP associated mortality.