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.

Phenotyping exercise limitation of patients with Interstitial Fibrosing Lung Disease: the importance of exercise hemodynamics.

INTRODUCTION AND OBJECTIVE: Left-heart dysfunction and pulmonary vasculopathy are increasingly recognized as contributing factors of exercise capacity limitation in interstitial fibrosing lung disease (IFLD). Moreover, the clinical significance of exercise pulmonary hypertension (ePH) in pulmonary and cardiac diseases has been documented, representing a risk factor for decreased exercise capacity and survival, progression to resting pulmonary hypertension (PH) and overall clinical worsening. We conducted a prospective study aiming at: (a) assessing the prevalence of PH and ePH in a cohort of 40 functionally limited patients with IFLD, (b) determining the post-capillary (postC) or pre-capillary (preC) etiology of either PH or ePH in this cohort, and (c) examining the correlations between invasively and non-invasively measured exercise variables among hemodynamic groups. PATIENTS AND METHODS: 40 IFLD patients underwent cardiopulmonary evaluation, including: clinical examination, lung function tests, 6-minute walking test, heart ultrasonography, cardiopulmonary exercise test and, finally, right heart catheterization (RHC). Resting hemodynamic evaluation was followed by the exercise protocol proposed by Herve et al, using a bedside cycle ergometer in the supine position. Abnormal elevation of mean pulmonary artery pressure (mPAP) above 30mmHg during exercise, with respect to abnormal elevation of cardiac output (CO) below 10 L/min (mPAP-CO ratio ⩾3 mmHg·min·L-1) was used to define ePH (Herve et al, 2015). Secondary hemodynamic evaluation involved detection of abnormal pulmonary arterial wedge pressure (PAWP) increase at peak exercise in relation to CO. Specifically, ΔPAWP/ΔCO >2 mmHg/L per minute determined an abnormal PAWP elevation (Bentley et al, 2020). RESULTS: Among the 40-patient cohort, 25% presented postC PH, 37.5% preC PH, 27.5% ePH, with the remaining 10% recording normal hemodynamics. PAWP evaluation during exercise revealed a postC etiology in 4 out of the 11 patients presenting ePH, and a postC etiology in 6 out of the 15 patients presenting resting preC PH. Mean values of non-invasive variables did not display statistically significant differences among hemodynamic groups, except for: diffusing capacity for carbon monoxide (DLCO), carbon monoxide transfer coefficient (KCO) and the ratio of functional vital capacity to DLCO (FVC%/DLCO%), which were lower in both ePH and PH groups (p < 0.05). Resting values of CO, cardiac index (CI), stroke volume (SV) and pulmonary vascular compliance (PVC) were significantly impaired in ePH, preC-PH and postC-PH groups when compared to the normal group. CONCLUSIONS: Both PH and ePH were highly prevalent within the IFLD patient group, suggesting that RHC should be offered more frequently in functionally limited patients. Diffusion capacity markers must thus guide decision making, in parallel to clinical evaluation. ePH was associated to lower resting CO and PVC, in a similar way to resting PH, indicating the relevance of cardiopulmonary function to exercise limitation. Finally, the use of the ΔPAWP/ΔCO>2 criterion further uncovered PH of postcapillary etiology, highlighting the complexity of hemodynamics in IFLD. CLINICALTRIALS: gov ID: NCT03706820.

Bronchoalveolar lavage fluid alteration in antioxidant and inflammatory status in lung cancer patients.

BACKGROUND: Increased oxidative and inflammatory markers have been reported in lung cancer patients, but relatively few studies have investigated the presence of antioxidants both in the local lung environment and in the systemic circulation. Furthermore, it is hypothesized that the immune system activation in vivo is regulated by the redox environment. OBJECTIVES: To investigate local and systemically circulating antioxidant and inflammatory mediators in lung cancer patients and potential correlations between them. METHODS: Forty two male patients (mean age 65±8years) with primary lung cancer were studied. Sixteen age and smoking history matched male subjects without any evidence of malignancy served as controls. Total antioxidant status (TAS) and glutathione (GSH), as well as interleukin-1a (IL-1a), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in bronchoalveolar lavage fluid (BALF) and serum samples. RESULTS: A statistically significant increase of TAS and GSH in BALF was observed in lung cancer patients compared to healthy subjects (0.27±0.24 vs. 0.12±0.02mmol/L, p=0.02 and 7.56±4.29 vs. 4.62±2.23µmol/L, p=0.01 respectively). Statistically significant correlations in cancer patients were observed in BALF between TAS and a. IL-1α (r=0.87, p<0.001), b. IL-6 (r=0.52, p=0.001) and c. TNF-α (r=0.67, p<0.001). CONCLUSIONS: Alteration in antioxidant and inflammatory mediator status was found in lung cancer patients both in serum and in BALF compared to healthy subjects matched for smoking history. Moreover, a positive correlation was observed between antioxidants and pro-inflammatory cytokines, but only locally and not systematically.

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.

Exophthalmos as a first manifestation of small cell lung cancer: a long-term follow-up.

Small cell lung cancer is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic therapy, until now treatments have failed to control or cure this disease in most patients. Orbital metastases are a rare manifestation of systemic malignancies. Breast and lung cancers represent more than two thirds of the primary cancer sites. Metastases to the eye and orbit develop in approximately 0.7-12% of patients with lung cancer. Here, we report a rare case of exophthalmos as the first manifestation of a metastatic carcinoma due to small cell lung cancer, and a 6-months follow-up with complete exophthalmic response to chemotherapy.

Bronchoalveolar lavage in children with inflammatory and non inflammatory lung disease.

BACKGROUND: Bronchoalveolar lavage (BAL) is a useful bronchoscopic technique. Studies in "normal" children are limited. AIM: To provide data on BAL reference values from Greek children and compare BAL cellular and noncellular components in children with inflammatory and non-inflammatory lung diseases. METHODS: Seventy two children, aged 2.5 months to 16 years, underwent diagnostic bronchoscopy and BAL. Patients were divided in two groups whether lung inflammation was absent or present. Differential cytology, flow cytometry for lymphocyte subsets and cytokine and chemokine measurements were performed on BAL fluid. RESULTS: Alveolar macrophages were the predominant cellular population in normal children. Patients with inflammatory pneumonopathies had significantly more neutrophils. There was no difference in lymphocyte subpopulations. Values of CD4+/CD8+ ratio in BAL was similar to that reported in adults. Levels of IL-8 and TNF- alpha were significantly higher in children with inflammatory lung diseases. CONCLUSION: This study provides the first data on BAL of "normal" Greek children. BAL from patients with pulmonary inflammation was characterised by neutrophilia. Finally, we propose that measurement of IL-8 and TNF-a levels in BAL could help in early identification of inflammation in the tracheobronchial tree.

Alterations of erythrocyte superoxide dismutase activity in patients suffering from asthma attacks.

BACKGROUND: Oxidant-antioxidant imbalance may play an important role in the development and progression of bronchial asthma. However, the role of blood antioxidants especially in asthma exacerbation has not been fully discussed. OBJECTIVE: This study examines a part of the intracellular antioxidant defense mechanism in asthmatic patients admitted to hospital due to severe exacerbation of their disease. METHODS: Peripheral blood Erythrocyte Superoxide Dismutase (SOD) activity was measured in 38 patients (33 men - 5 women, with a mean age of 56 +/- 2.8 yrs), using a colorimetric method. On the days of admission and discharge the Forced Expiratory Volume in 1 second (FEV1) and the Partial arterial Oxygen pressure (PaO2) were recorded and correlated with SOD activity at the same time. RESULTS: A statistically significant decrease of SOD activity was observed on the day of admission compared to SOD activity on the day of discharge (43.64 +/- 31.78 vs. 96.16 +/- 54.05 units/ml, p < 0.001), suggesting the presence of oxidative stress during an asthma attack. A statistically significant correlation was observed between FEV1 on admission and SOD activity at the same time (r = 0.57, p < 0.001). Furthermore, SOD activity on admission was correlated with PaO2 on discharge (r = 0.55, p < 0.001), as well as SOD on discharge with PaO2 on discharge (r = 0.53, p = 0.001). CONCLUSIONS: Decreased systemic erythrocyte SOD activity was observed during asthma attacks. This activity was correlated with severity criteria such as FEV1 and PaO2. Therefore, it seems that measurement of SOD activity could be a useful tool in the evaluation of an asthma attack. The supplementary administration of antioxidants in the future needs further clarification.

Epidemiology of interstitial lung diseases in Greece.

INTRODUCTION: Few data are available on the epidemiology of interstitial lung diseases (ILDs), especially after the current classification of idiopathic interstitial pneumonias. The aim of this study is to provide data on the epidemiology of ILDs in Greece, under the ATS/ERS international consensus. METHODS: Departments of Pneumonology were contacted and asked to complete a questionnaire for every case of ILD that was alive on 2004 as well as for every new case from 1st January 2004 to 31st December 2004. Questions on the patients' demographic data, the exact diagnosis and the procedures used to establish the diagnosis were included. Centers covering about 60% of the Greek population have been analyzed. RESULTS: A total of 967 cases have been registered. The estimated prevalence of ILDs is 17.3 cases per 100,000 inhabitants. The estimated annual incidence of ILDs is 4.63 new cases per 100,000 inhabitants. The most frequent disease is sarcoidosis (34.1%), followed in decreasing order by idiopathic pulmonary fibrosis (19.5%), ILD associated with collagen vascular diseases (12.4%), cryptogenic organizing pneumonia (5.3%), histiocytosis (3.8%), and hypersensitivity pneumonitis (2.6%). Unclassified ILD or not otherwise specified accounted for the 8.5% of prevalent cases. CONCLUSIONS: These data suggest that sarcoidosis and idiopathic pulmonary fibrosis are the most frequent ILDs in our population. In comparison with the few previous reports, interesting dissimilarities have been observed.

Bronchoalveolar lavage fluid eosinophils are correlated to natural killer cells in eosinophilic pneumonias.

BACKGROUND: Eosinophilic lung diseases comprise a group of heterogeneous pulmonary disorders linked by increased eosinophils in bronchoalveolar lavage fluid (BALF). There is supporting evidence that natural killer (NK) cells participate in the regulation of eosinophilic inflammation. OBJECTIVE: Our aim was to investigate the relationship between eosinophils and NK cells in BALF in patients with different interstitial lung diseases (ILDs) focusing on eosinophilic pneumonias. METHODS: Of 114 patients who presented with increased BALF eosinophils (>5%), 74 patients were classified into the following groups: 27 had eosinophilic pneumonia (EP), 17 had idiopathic pulmonary fibrosis (IPF), 16 had hypersensitivity pneumonitis (HSP) and 14 had cryptogenic organizing pneumonia (COP/BOOP). Total BALF cells, cell density and cell differential counts were assessed and lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK) and CD3+CD16/56+ (NKT) were determined by flow cytometry. RESULTS: Significant differences were observed in the percentages of lymphocytes (p < 0.001) and CD3+CD16/56+ cells (p = 0.023) among patient groups. In patients with EP, the percentage of eosinophils correlated positively with the number of CD3-CD16/56+ cells (r = 0.522, p = 0.005), the percentage of CD3-CD16/56+ cells (r = 0.690, p < 0.001), and the absolute count of CD3+CD16/56+ absolute cells (r = 0.609, p = 0.001). However, in patients with IPF, HSP or COP/BOOP, no correlation between the percentage of eosinophils and CD3-CD16/56+ or CD3+CD16/56+ cells was observed. CONCLUSIONS: Eosinophil inflammation seems to develop through a different pathway in EP compared to other ILDs.

Epidemiologic trends in lung cancer over two decades in Northern Greece: an analysis of bronchoscopic data.

BACKGROUND AND AIM: The relative frequency of histological subtypes of lung cancer in Europe has changed dramatically during the 20th century. The aim of this study was to explore the changing epidemiology of lung cancer in Northern Greece over the last two decades. METHODS: From the extensive database of the Bronchoscopy Unit of the G. Papanicolaou General Hospital, Thessaloniki, Greece, we identified all patients with a histologic and/or cytologic report positive for lung cancer over two consecutive decades. RESULTS: Between 1/1/1986 and 31/12/2005 we identified 9981 patients with specimens positive for lung cancer. A significant increase in mean patient age was observed during the second decade (64.8 +/- 9.4 vs. 62.1 +/- 8.9, p=0.001). Men developed lung cancer ten times more often than women. The predominant histological type was squamous cell cancer in males (4203 cases, 45.7%) and adenocarcinoma (418 cases, 52.6%) in females. The number of lung cancer cases was significantly higher during the second decade compared to the first decade (5766 cases [57.8%] vs. 4215 cases [42.2%], respectively, p<0.001). There was a significant decrease in the percentage of squamous cell carcinoma in males in the second decade (2317 cases [44.1%] vs. 1886 cases [48.0%], p<0.001), and an increase in adenocarcinoma (1021 cases [19.4%] vs. 609 [11.6%], p<0.001). In females, the relative incidence of adenocarcinoma was decreased and that of squamous cell carcinoma was increased, but not significantly. There was no obvious change in the incidence of small cell lung cancer. Neoplastic lesions were most often located in the upper lobes. CONCLUSION: The number of lung cancer cases has increased in the last decade. Squamous lung cancer appears to be decreasing in men and increasing in women. Adenocarcinoma appears to be increasing in men and decreasing in women. There appears to be no change in small cell lung cancer. During the second decade there has been a significant decrease in the male: female ratio.

Changes in soil characteristics and plant species composition along a moisture gradient in a Mediterranean pasture.

Soil physicochemical characteristics, total aboveground biomass, number of species and relative abundance of groups and individual species were measured along a moisture gradient in a pasture, flooded in part during winter through early summer, adjacent to Pamvotis lake in Ioannina, Greece. Soil and vegetation measurements were conducted in 39 quadrats arranged in four zones perpendicular to the moisture gradient. The zone closest to the lake, recently separated from the lake, became part of the pasture and its soil texture was quite different from that of the other zones with a substrate containing 91% sand. Except for pH, this zone had the lowest values in the other five soil physicochemical characteristics measured (organic matter, total and extracted inorganic nitrogen, Olsen extracted phosphorus and extractable potassium); in the other zones organic matter, total nitrogen, phosphorus and potassium tended to increase from the driest to the wettest zone. Total aboveground biomass, ranging from 280 to 840 gm-2, is high for herbaceous pastures in the conditions of Mediterranean climate and it was not related to distance from the lake's shoreline, although the highest values were measured at intermediate distances, or to any of the various soil characteristics measured. Also, the number of species/0.25 m2 was not related to any of the various soil characteristics, but it was highest at the intermediate distances from the lake's shoreline. Species composition varied along the moisture gradient. Forbs as well as annual grasses and legumes declined in abundance from the driest to the wettest places; the reverse was the case for sedges and perennial grasses and legumes. These results indicate that the soil moisture gradient was the principal factor affecting soil characteristics and plant species composition. Since most species were recorded in all the four zones of the pasture, indicating that these can tolerate all variations in abiotic conditions of pasture, the vegetation zonation seems to be influenced by competition. Each functional group of species tends to dominate in a particular range of the soil moisture gradient where it is better suited and tends to exclude competitively other species. Management practices (mowing and grazing) affect the kinds of processes which maintain the observed community structure either by preventing the establishment of later successional species, like reeds and woody species, or by moderating the shoot competition, especially in the wetter zones, and thus permitting the creeping species to grow successfully.

Allergenic fungi spore records (15 years) and sensitization in patients with respiratory allergy in Thessaloniki-Greece.

BACKGROUND: The prevalence of respiratory allergy to fungi spores (FS) is not precisely known but is estimated at 20-30% of atopic patients. There are no aerobiological records, necessary for respiratory allergy diagnosis and treatment, in Thessaloniki and generally in Greece. AIM: Creation of a database on FS circulation and investigation of skin sensitivity (SS) of asthmatics by using skin prick tests (SPT). MATERIAL AND METHODS: Daily records and identification of 15 airborne FS species were conducted, using a Burkard trap during 1987-2001. SS to 5 most common FS extracts was investigated, by using SPT in a total of 1311 asthmatics with atopy, submitted to the Out-Patient Clinic of Asthma (Pulmonary Dept, Aristotle Univ, Thessaloniki) in 1990-2001. RESULTS: The FS recorded in the 15-year period were as follows: Cladosporium spp. (72.2%), Alternaria spp. (9.8%), Ustilago spp. (8.1%), Ascospores (2.7%), Agrocybe spp. (1.5%), Helminthosporium spp. (1.4%), Leptosphaeria spp (1.2%), Agrogybe spp. (1.1%), whereas the species Botrytis, Stemphylium, Pleospora, Nigrospora, Epicoccum. Fusarium, Torula and Phoma presented concentrations <1%. The highest numbers of airborne FS were recorded during summer. Positive skin reaction to FS was observed in 421 (32%) patients of the 1311 asthmatics. Positive skin reaction to Altemaria species was observed in 177 patients (13.5%), in 98 (7.4%) to Cladosporium, 65 (5%) to Aspergillus, 45 (3.4%) to Fusarium and 36 (2.7%) to Rhizopus. FS sensitivity is much more frequent in younger men. CONCLUSIONS: For the first time in Thessaloniki-Greece, 15 allergenic FS species circulation has been recorded for the last 15 years. SS was more frequently detected for the species of Alternaria, Cladosporium and Aspergillus.

Allergenic pollen records (15 years) and sensitization in patients with respiratory allergy in Thessaloniki, Greece.

BACKGROUND: Very limited allergenic pollen records exist in Greece so far; moreover, there is a lack of investigation on patient sensitization. The above data are necessary for respiratory allergy diagnosis and treatment worldwide. METHODOLOGY: Daily records and identification of 16 airborne pollen species were made using a Burkard trap (1987-2001). Skin sensitivity to 13 most common pollen extracts was investigated, in a sample of 1311 asthmatics with atopy, admitted to the Out-Patient Clinic for Asthma (1990-2001). Skin sensitivity to 55 allergens, including 13 pollen extracts, was detected by skin prick test. RESULTS: The following pollen concentrations were recorded: cypress (24.9% of the total), oak (20.8%), wall pellitory (13.6%), olive (9.1%), pine (8.9%), grasses (6.3%), plane (5.4%), hazel (3%), goosefoot (2.5%) and poplar (1.4%). The respective percentages of birch, ragweed, mugwort, willow, alder and elm were lower than 1%. The highest counts of airborne pollen grains were detected from March to June. Regarding patient sensitization, sensitivity was detected to: grasses in 530 patients (40.4%), olive 417 (31.8%), goosefoot 240 (18.3%), wall pellitory 201 (15.3%), mugwort 198 (15.1%), plantain 194 (14.6%), cypress 166 (12.7%), hazel 126 (9.6%), pine 122 (9.3%), poplar 111 (8.4%), plane 107 (8,2%), oak 99 (7.6%) and to birch 89 patients (6.8%). The sensitivity to pollen grains displays preponderance (57.9%) to males. CONCLUSIONS: For the first time in Thessaloniki, Greece, 15-year allergenic pollen records were conducted. Clinical observations confirm that the pollen mainly implicated in respiratory allergy symptoms are grasses, olive and wall pellitory.

15-year aeroallergen records. Their usefulness in Athens Olympics, 2004.

INTRODUCTION: About 5-25% of 16 000 athletes involved in preparation for the Athens 2004 Olympics may encounter respiratory allergy (asthma and rhinoconjunctivitis) triggered by exposure to aeroallergens (pollen and fungi spores). AIM: Provide information about circulating aeroallergens in three Olympic cities and ensure safety for the allergic athletes who will visit Greece from January to September 2004. METHODS: Aeroallergens were recorded using a Burkard volumetric trap. The most frequently implicated pollen (cypress, hazel, wall pellitory, plane, olive, grasses, goosefoot and mugwort) and fungi spores (Alternaria spp., Cladosporium spp.) are presented. These data derive from a 15-year database created by the Pulmonary Department, Thessaloniki, a 2-year database (University of Heraklion-Crete) and a 6-year database by the Pediatric Department, Athens. The above data and the current aeroallergen counts will be continuously announced by the mass media and Internet during the Athens 2004 Olympics. RESULTS: Are expressed as: (A) Presentation (Graphs, Tables) of the fluctuation of mean daily values of pollen grains or fungi spores/m3. (B) Presentation (Tables) of the start, peak and end time of aeroallergen circulation. Peak pollen concentrations were observed between March and May (athletes preparation time). During the 2004 Olympics (August-September) relatively high concentrations of goosefoot, mugwort, Alternaria and Cladosporium will be observed. Aeroallergens circulate in Athens 10-15 days earlier than in Thessaloniki and 10 days later than in Heraklion. CONCLUSIONS: The data presented in the study are expected to help allergic Olympic athletes achieve peak performance under prophylactic measures.

A comparison of the clinical efficacy and patient acceptability of terbutaline Turbuhaler and salbutamol Rotahaler, in adult patients with asthma.

This open randomized, cross-over study compared the clinical efficacy and patient acceptability of the two bronchodilator delivery systems, terbutaline Turbuhaler (0.5 mg t.i.d.) and salbutamol Rotahaler (0.4 mg t.i.d.), each given for 3 weeks. Thirty-two adult asthmatics (21 males and 11 females with a mean age of 34 years) who demonstrated at least 15% reversibility in PEF or FEV1 in response to terbutaline, were enrolled for study. The median reversibility in FEV1 was 27.5% for the terbutaline-salbutamol group and 21% for the salbutamol-turbutaline group. Two patients discontinued during terbutaline treatment (one due to respiratory infection and one due to tachycardia, exhaustion and tremor) and five patients were lost to follow-up during salbutamol treatment, leaving data from 25 patients for an 'all patients treated' analysis. Mean morning PEF was 426 l min-1 during terbutaline and 410 l min-1 during salbutamol (difference 16 l min-1, 95% CI of difference 3-28 l min-1, P = 0.016), and mean evening PEF was 446 l min-1 during terbutaline and 428 l min-1 during salbutamol (difference 18 l min-1, 95% CI 5-30 l min-1, P = 0.0076). No significant differences were detected in diary symptom scores or in use of additional study drug during the day or night, and no serious adverse events were reported. When asked to state their treatment preferences on the basis of effects, side-effects and overall, more patients preferred Turbuhaler in each case, although no statistically significant differences were detected. In conclusion, terbutaline via Turbuhaler was significantly more effective than salbutamol via Rotahaler in controlling lung function (mean daily PEF) in adults with mild to moderate asthma, and it was the preferred treatment overall in 44% of patients, compared with 16% for Rotahaler (n.s.).

Influence of pindolol on asthmatics and effect of bronchodilators.

Bronchospasm is a known side effect of the administration of beta-blockers to asthmatics. The purpose of this study was to investigate the frequency of bronchospasm caused by the administration of relatively low doses (2.5-7.5 mg) of pindolol, a beta-blocker with intrinsic sympathetic activity (ISA) to asthmatics, the severity of the bronchospasm and its reversibility and the probable correlations of bronchial asthma (BA) characteristics (severity, duration, allergy and airway hyperreactivity) with existing or nonexisting bronchospasm. Seventeen asthmatic patients: 10 men and 7 women, with a mean age of 44 +/- 10 years, participated in this study. The duration and severity of BA, the presence of allergy determined by skin tests and the bronchial hyperreactivity to methacholine inhalation challenge were observed on the first day of study. On the following days, the respiratory function parameters forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), and the pulse rate were measured before and 30, 60 and 90 min after the administration of placebo and pindolol. Then salbutamol was administered by a dosimetric aerosol (DA) at the usual dosage (200 micrograms) and the change in FEV1 was observed at 60 min; thereafter 40 micrograms of ipratropium bromide (IB) were administered by DA and FEV1 was measured after 60 min. Pindolol was administered gradually by mouth (2.5 mg every 30 min), the maximal total dose being 7.5 mg. Administration of pindolol caused a significant fall of FEV1 of 12 +/- 11% compared to placebo. A significant total decrease of FEV1 (greater than or equal to 20% of baseline) was observed in 9 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ipratropium bromide on repeated methacholine challenges.

The purpose of this study was to trace the protective effect of ipratropium bromide (IB) during methacholine inhalation challenge (MIC) at the first and fourth hour after its administration. IB-inhaler contains 0.02 mg IB in each puff and it was used in the usual dosage of two puffs (0.04 mg). In 20 asthmatic patients, the dose of methacholine caused a drop in FEV1 of 20% (PD20-FEV1). It was concluded that IB protected patients significantly one hour after its administration and showed a significant bronchodilating effect in comparison to placebo. IB protected 19 of the 20 patients one hour after administration during MIC while placebo protected none. IB protected 13 of the 20 patients, after the second PD20-FEV1 with methacholine, four hours after its administration.