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.

Telomere length across different UIP fibrotic-Interstitial Lung Diseases: a prospective Greek case-control study.

INTRODUCTION: Short telomeres are recognized as risk factor for idiopathic pulmonary fibrosis (IPF). We aimed to assess the role of telomere length (TL) in fibrotic-Interstitial Lung Diseases (f-ILDs) associated with a usual interstitial pneumonia (UIP) pattern as well as in IPF acute exacerbation (IPF-AE). AIM AND METHODS: TL was measured from peripheral white blood cells using a multiplex quantitative polymerase chain reaction in consecutive patients with f-ILDs, all presenting UIP pattern in the high-resolution chest-computed-tomography and compared to age-matched healthy controls. RESULTS: Seventy-nine individuals were included (mean age 69.77 ±â€¯0.72 years); 24 stable IPF, 18 IPF-AE, 10 combined pulmonary fibrosis and emphysema, 7 Rheumatoid arthritis-UIP-ILDs and 20 controls. TL in all patients was significantly shorter compared to controls [mean T/S ratio (SE) 0.77 (±0.05) vs 2.26 (±0.36), p < 0.001] as well as separately in each one of f-ILD subgroups. IPF-AE patients presented significantly shorter TL compared to stable IPF (p = 0.029). Patients with IPF and shorter than the median TL (0-0.72) showed reduced overall survival (p = 0.004). T/S < 0.72 was associated with increased risk for IPF-AE (OR = 30.787, 95% CI: 2.153, 440.183, p = 0.012) independent of age, gender, smoking and lung function impairment. A protective effect of TL was observed, as it was inversely associated with risk of death both in UIP-f-ILDs (HR = 0.174, 95%CI: 0.036, 0.846, p = 0.030) and IPF patients (HR = 0.096, 95%CI: 0.011, 0.849, p = 0.035). CONCLUSIONS: Shorter TL characterizes different UIP f-ILDs. Although no difference was observed in TL among diverse UIP subgroups, IPF-AE presented shorter TL compared to stable IPF. Reduced overall survival and higher hazard ratio of death are associated with shorter TL in IPF.

Depression, physical activity, energy consumption, and quality of life in OSA patients before and after CPAP treatment.

BACKGROUND: A variety of studies have demonstrated improvement in quality of life and depressive symptoms in obstructive sleep apnea (OSA) patients after continuous positive airway pressure (CPAP) treatment. However, very little is known about the effect of OSA treatment on physical activity and energy consumption. OBJECTIVES: The aim of this study was to evaluate the changes in depression, physical activity, energy expenditure, and quality of life (QoL) in OSA patients before and after CPAP therapy. METHODS: Forty-one patients with OSA as revealed by polysomnography, were included to the study. They responded to the generic World Health Organization Quality of Life (WHOQoL) questionnaire, to the specific-disease Quebec Sleep Questionnaire, and to Center for Epidemiologic Studies Depression Scale (CES-D) in order to evaluate QoL and the incidence of depression. In addition, all patients wore an accelerometer which measured physical activity and energy expenditure during a week. At least 6 months after initiation of CPAP treatment (mean time, 9 months) we re-examined 24 patients who met the compliance with the treatment criteria. RESULTS: Patients after CPAP therapy had significantly higher scores in all domains of the Quebec Sleep Questionnaire and in the domains of physical health/level of independence and psychological health/spirituality of the WHOQoL. Depression scores were also better in CES-D after treatment. However, despite the improvement in QoL and psychological status, CPAP therapy had no impact on physical activity and energy expenditure. CONCLUSIONS: CPAP therapy improves QoL and lessens depressive symptoms in our group of well-treated OSA patients. However, physical activity and energy expenditure did not present statistically significant improvement in the same group of OSA patients.

Mycobacterium kansasii endobronchial ulcer in a nonimmunocompromised patient.

In this report we describe the case of an immunocompetent patient found to have an endobronchial, ulcerated lesion due to Mycobacterium kansasii. Predisposing factors could have been severe endobronchial stenosis of the main stem bronchi and distortion of the carina, due to healed endobronchial tuberculosis. Diagnosis was set through fiberoptic bronchoscopy and the patient responded well to treatment. Endobronchial non tuberculous mycobacterial infection should be considered in both HIV seropositive and seronegative patients, especially in endemic areas and in the proper clinical setting. Prompt recognition is important for the effective control and prevention of an unfavorable outcome in an otherwise easily treatable disease.