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.

Disseminated Bacillus Calmette-Guerin infections after intravesical therapy.

Intravesical instillation of Bacillus Calmette-Guerin (BCG) is the treatment of choice for superficial bladder carcinoma. Disseminated BCG infection presenting as granulomatous hepatitis or pneumonitis is a very rare complication of this treatment. Here we report a case series of seven patients previously treated with BCG presenting with pneumonitis. In two of the cases, identification of Mycobacterium bovis was achieved with molecular methods.

Epidemiology and clinical significance of mycobacterial respiratory infections in Central Greece.

SETTING: A 750-bed tertiary referral hospital in Central Greece. OBJECTIVE: To determine the incidence of non-tuberculous mycobacteria (NTM) respiratory infection based on the isolation of NTM in respiratory specimens, to study their clinical significance and to evaluate the differences in clinical, radiological and demographic characteristics between patients with lung disease caused by NTM and that caused by Mycobacterium tuberculosis complex (MTC). DESIGN: A 3-year period prospective study to identify patients with positive NTM and MTC respiratory specimens. RESULTS: Between January 2004 and December 2006, 564 positive NTM cultures from 214 patients and 118 MTC cultures from the same number of patients were collected. The incidence rate of clinically significant NTM lung infection was 0.67, 0.54 and 0.94 cases per 100,000 population, and that of MTC infection of the lung was respectively 5.70, 5.28 and 5.10 cases/100,000 in the three study years. Smoking habits and chronic obstructive pulmonary disease were significant risk factors for NTM disease (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: NTM incidence rates were lower than those reported in the rest of Europe and the USA. Further studies are needed to determine the prevalence and the significant geographic variability of NTM and their clinical significance at the national level.

Could IFN-gamma predict the development of residual pleural thickening in tuberculous pleurisy?

BACKGROUND: The aim of our study was to identify predictive factors for the development of residual pleural thickening (RPT) in patients with tuberculous pleurisy (TP). METHODS: A retrospective study of patients with pleural tuberculosis. The clinical and radiological characteristics, and measurements of microbiological and biochemical parameters or markers such as adenosine deaminase (ADA), interferon-gamma (IFN-gamma) and vascular endothelial growth factor (VEGF) in pleural fluid were studied. RESULTS: Thirty one patients (24 male and 7 female) with a mean age of 55.9 years were studied. There were 25 (80.6%) patients with RPT > 2 mm and 6 (19.4%) patients without RPT. Ten patients (32.2%) had RPT > or = 10 mm. The rate of pleural thickening was less in small effusions (p<0.05). IFN-gamma was higher in patients with RPT > or = 10 mm (p < 0.05) in comparison with those with RPT < 10 mm. CONCLUSIONS: Pleural fluid IFN-gamma may deserve further investigation in order to build up preventive and therapeutic strategies against RPT and its clinical complications.

Increased prevalence of irritable bowel syndrome in patients with bronchial asthma.

Irritable bowel syndrome (IBS) is one of the most common diseases of the gastrointestinal tract. IBS may represent a primary disorder of gastrointestinal motility accompanied with motor dysfunction in various extraintestinal sites. Recent studies suggest that IBS is associated with bronchial hyper-responsiveness and bronchial asthma might be more prevalent in IBS patients than in control subjects. The aim of our study was to assess the prevalence of IBS in a cohort of asthmatic patients. We evaluated 150 patients with bronchial asthma (71 males and 79 females, aged 45.1+/-14.9 years) and two control groups including 130 patients with other pulmonary disorder and 120 healthy subjects. All subjects enrolled (asthmatic and controls) completed the Greek version of the Bowel Disease Questionnaire (BDQ). BDQ is a, previously validated, self-report instrument to measure gastrointestinal symptoms. Diagnosis of IBS was based on Rome II criteria. The IBS prevalence was significantly higher in asthmatics (62/150, 41.3%) than in subjects with other pulmonary disorders (29/130, 22.3%, P<0.001) and healthy ones (25/120, 20.8%, P<0.001). For all subjects studied, the prevalence of IBS was significantly higher in females (78/214, 36.4%) than in males (38/186, 20.4%, P<0.001). The IBS prevalence in asthmatic males was 29.5% vs. 15.2% in male patients with other pulmonary disorders (P=0.002) and 14.2% in male healthy subjects (P=0.002). The IBS prevalence in asthmatic females was 51.8% vs. 28.1% in females patients with other pulmonary disorders (P<0.001) and 26.5% in females healthy subjects (P<0.001). None of the asthma medications were associated with increased or decreased likelihood of IBS. We conclude that patients with bronchial asthma have an increased prevalence of IBS. Further studies are needed to clarify the potential pathogenetic mechanisms underlying the association between IBS and asthma.