Advances in asthma and COPD management: delivering CFC-free inhaled therapy using Modulite technology.

Inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are currently used in the management of asthma and chronic obstructive pulmonary disease (COPD). Localized targeted delivery of these drugs into the lungs is achieved by means of two types of inhalation devices; pressurized metered-dose inhalers (pMDIs) and dry powder-inhalers (DPIs). For environmental reasons, the chlorofluorocarbon (CFC) propellants used in pMDIs are now being replaced by ozone friendly hydrofluoroalkanes (HFAs). These new generation HFA-based pMDIs, developed to provide effective lung deposition of the active moiety, have a favorable safety and tolerability profile. However, HFA-based re-formulation of LABAs and ICS for pMDIs presents particular technical difficulties, especially in terms of ensuring dose content uniformity. This review focuses on the technology and clinical efficacy of the HFA solution pMDIs using Modulite platform technology (Chiesi Farmaceutici S.p.A). Modulite technology allows the development of HFA solution formulations that can mimic the established CFC-based drug formulations on a microgram to microgram basis and provides formulations with novel particle size distributions that improve on existing delivery systems; by manipulation of aerosol clouds and particle size, the delivery of HFA-formulated drugs can be optimized to either achieve fine particle fractions and deposition patterns similar to established CFC-based drug formulations, thus facilitating the transition to new environment-friendly pMDIs in the clinical setting, or achieve finer drug particles able to penetrate deeper into the bronchi for targeted drug delivery as medical need may dictate. Long-term, multiple-dose clinical studies of Modulite formulations of beclomethasone dipropionate (BDP), budesonide and formoterol have been demonstrated to be therapeutically equivalent to their respective previously established CFC or DPI formulations. As a result, a number of Modulite pMDIs have either recently gained regulatory approval in several European countries, or have completed clinical trials and are in the regulatory submission phase. Availability, in pMDI form, of drugs like formoterol, ICSs, and ICS/LABA combinations, all central to the effective management of asthma and COPD, is therefore expected to impact positively in assuring the continued availability of vital treatment options to patients and physicians.

The effects of environmental pollution on the respiratory system of children in western Macedonia, Greece.

The indoor and outdoor environmental pollution effects on the respiratory system of 3,559 children aged 9-12 were studied. It was a cross-sectional and interlocal (geographical differentiation) study. The research was conducted during the period between 2000-2001 in five cities of Western Macedonia and more particularly: 1046 children from Ptolemaida, 1249 children from Kozani, 466 from Florina, 419 from Kastoria and 379 from Grevena. The study was performed by means of a questionnaire for the detection of respiratory diseases during childhood, plus spirometry and rhinomanometry measurements. The diachronic quantitative analysis of environmental pollutants was conducted by The Laboratory of Physics of the Atmosphere of the Aristotle University of Thessaloniki. The environmental pollution was found to have a detrimental effect on the respiratory system of children, mainly attributable to the occurrence of rhinitis and infectious bronchitis. The highest prevalence of rhinitis (40.3%) and infectious bronchitis (12.1%) was observed in Ptolemaida, which is a highly polluted region, whereas the lowest (21.2% and 6.7%, respectively) was seen in Grevena, a non-polluted area. As for the indoor pollution, maternal smoking was found to increase the prevalence of respiratory problems in children. Finally, the father's educational level and a past history of nursery school attendance increase the prevalence of respiratory diseases during childhood.

Prevalence of chronic obstructive pulmonary disease and rhinitis in northern Greece.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) constitutes one of the main factors responsible for morbidity and mortality worldwide. Rhinitis has a high prevalence, but its relationship to COPD has not been determined. OBJECTIVES: To estimate the prevalence of COPD and rhinitis in northern Greece and to examine their correlation. PATIENTS AND METHODS: Of a total of 8,151 subjects (aged 21-80 years, from three regions of northern Greece) invited to participate in the study, 6,112 (75%) were included. The regions studied were: (a) Thessaloniki (1,733 study participants, 52.7 +/- 18.6 years old), an urban area with particulate air pollution frequently exceeding the acceptable limit, (b) Eordea (3,537 study participants, 51.4 +/- 15.5 years old), a typical industrial area with particulate air pollution with daily values exceeding the acceptable limit and (c) Grevena (842 study participants, 55.6 +/- 15.4 years old), a mountainous area without pollution. The study participants filled in the questionnaire on respiratory symptoms of the Committee on Environmental and Occupational Health of the Medical Research Council and underwent spirometry and rhinomanometry tests. RESULTS: The prevalence of COPD was 5.6% (8.2% in men and 2.5% in women) and that of rhinitis 24.7% (27.4% in men and 21.4% in women). COPD and rhinitis are related to common predisposing factors (smoking, age and sex). Moreover, rhinitis is related to particulate air pollution levels. CONCLUSIONS: The prevalence of COPD and rhinitis in northern Greece does not differentiate from that found in other industrial countries. A functional relationship between upper and lower airways is speculated.

Respiratory effects in workers processing dried tobacco leaves.

OBJECTIVES: The aim of this study was to examine the pollution level of the occupational environment and to investigate the effects of occupational exposure to tobacco dust on the respiratory system of tobacco workers. No such study has previously been conducted in Greece, which is one of the main tobacco-producing countries. METHODS: A total of 1,020 seasonal and permanent tobacco workers (188 men and 832 women) were studied in a factory in Thessaloniki. The study included: 1) completion of a questionnaire (British Medical Research Council 1986), 2) spirometry and 3) rhinomanometry. At the same time, tobacco dust levels in the working environment were measured. As controls, 469 workers (87 men and 382 women) at a Thessaloniki hospital were used. Seventy six workers with nasal symptoms underwent: 1) special nasal provocation test with tobacco dust antigen, 2) skin prick tests, and 3) measurement of total IgE, specific IgE and specific IgG against tobacco protein. RESULTS: Very high levels of total suspended dust were found in work site air (45.3-54.4 mg/m3). The prevalence of chronic bronchitis was 8.7 % versus 20.6 % in controls. Chronic obstructive pulmonary disease was found in 13 workers (1.3 %) and in 16 controls (3.4 %). FEV1 %pred, FVC %pred and the FEV1/FVC ratio were lower in controls, whereas FEF25-75 % %pred was lower in workers. There were no workers with bronchial asthma or extrinsic allergic alveolitis. Rhinitis was reported by 27.3 % of the workers versus 17.9 % of controls, whereas nasal flows were 563+/-211 versus 645 +/- 321 ml/sec, respectively. According to the results of skin prick tests, six workers were sensitized to dried tobacco leaf dust. CONCLUSIONS: The results of our study do not support an association between the development of chronic diseases of the lower respiratory system and pollutants associated with the processing of dried tobacco leaves. In contrast, an association between disorders of the upper airways and tobacco dust in work sites is postulated.

Respiratory effects in workers processing dried tobacco leaves

Objectives: The aim of this study was to examine the pollution level of the occupational environment and to investigate the effects of occupational exposure to tobacco dust on the respiratory system of tobacco workers. No such study has previously been conducted in Greece, which is one of the main tobacco-producing countries. Methods: A total of 1,020 seasonal and permanent tobacco workers (188 men and 832 women) were studied in a factory in Thessaloniki. The study included: 1) completion of a questionnaire (British Medical Research Council 1986), 2) spirometry and 3) rhinomanometry. At the same time, tobacco dust levels in the working environment were measured. As controls, 469 workers (87 men and 382 women) at a Thessaloniki hospital were used. Seventy six workers with nasal symptoms underwent: 1) special nasal provocation test with tobacco dust antigen, 2) skin prick tests, and 3) measurement of total IgE, specific IgE and specific IgG against tobacco protein. Results: Very high levels of total suspended dust were found in work site air (45.3-54.4 mg/m3). The prevalence of chronic bronchitis was 8.7 % versus 20.6 % in controls. Chronic obstructive pulmonary disease was found in 13 workers (1.3 %) and in 16 controls (3.4 %). FEV1 %pred, FVC %pred and the FEV1/FVC ratio were lower in controls, whereas FEF25-75 % %pred was lower in workers. There were no workers with bronchial asthma or extrinsic allergic alveolitis. Rhinitis was reported by 27.3 % of the workers versus 17.9 % of controls, whereas nasal flows were 563±211 versus 645 ± 321 ml/sec, respectively. According to the results of skin prick tests, six workers were sensitized to dried tobacco leaf dust. Conclusions: The results of our study do not support an association between the development of chronic diseases of the lower respiratory system and pollutants associated with the processing of dried tobacco leaves. In contrast, an association between disorders of the upper airways and tobacco dust in work sites is postulated (AU)

Objetivos: El propósito del estudio era examinar el nivel de contaminación del entorno de trabajo e investigar los efectos de la exposición laboral al polvo de tabaco sobre el aparato respiratorio de los trabajadores de la industria tabacalera. Fue el primer estudio de estas características realizado en Grecia, uno de los principales países productores de tabaco. Métodos: Se estudiaron los casos de 1.020 trabajadores temporales y permanentes de la industria tabacalera (188 hombres y 832 mujeres) en una fábrica de Tesalónica. El estudio consistió en los siguientes pasos: 1) cumplimentar un cuestionario (Consejo Bri- tánico de Investigaciones Médicas, 1986); 2) espirometría, y 3) rinomanometría. Al mismo tiempo, se midieron los niveles de polvo de tabaco en el entorno de trabajo. Se emplearon como controles 469 trabajadores (87 hombres y 382 mujeres) del hospital de Tesalónica. Se sometieron 76 trabajadores con síntomas nasales a los siguientes procedimientos: 1) prueba de provocación nasal especial con polvo de tabaco como antígeno; 2) pruebas cutáneas, y 3) medición de la IgE total, la IgE específica y la IgG específica contra proteína de tabaco. Resultados: En el aire del entorno de trabajo se observaron niveles muy elevados de polvo suspendido total (45,3-54,4 mg/m3). La prevalencia de la bronquitis crónica era del 8,7 por ciento, frente al 20,6 por ciento de los controles. Se observó enfermedad pulmonar obstructiva crónica (EPOC) en 13 trabajadores (1,3 por ciento) y en 16 controles (3,4 por ciento). Los valores del porcentaje predicho de FEV1y FVC, así como el cociente FEV1/FVC resultaron inferiores en los controles, mientras que el porcentaje predicho de FEF25-75 por ciento era inferior en los trabajadores. Ningún trabajador presentaba asma bronquial ni alveolitis alérgica extrínseca. Se observó rinitis en un 27,3 por ciento de los trabajadores frente al 17,9 por ciento de los controles, mientras que los flujos nasales resultaron ser de 563ñ211 frente a 645ñ321 ml/seg, respectivamente. Según las pruebas cutáneas, 6 trabajadores presentaban sensibilidad al polvo de las hojas secas de tabaco. Conclusiones: Los resultados de nuestro estudio no respaldan una relación entre el desarrollo de enfermedades crónicas del tracto respiratorio inferior y los contaminantes asociados a la manipulación de hojas secas de tabaco. En cambio, se postula una asociación entre los trastornos del tracto respiratorio superior y el polvo de tabaco de los entornos de trabajo (AU)

Penetration of newer quinolones in the empyema fluid.

The degree of penetration of newer quinolones into the pleural fluid has not been studied. The objective of the present study was to determine the degree to which moxifloxacin and levofloxacin penetrate into empyemic pleural fluid using a new rabbit model of empyema. An empyema was created via the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 2 mL (1 x 10(10)) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, moxifloxacin and levofloxacin (25 mg.kg(-1) for both, i.v.) were administered. Antibiotic levels were determined in samples of pleural fluid and in blood collected serially over 12 h. Antibiotic levels were measured using HPLC. Each of the antibiotics penetrated well into the empyemic pleural fluid. Antibiotic penetration was the greatest for moxifloxacin (area under the curve (AUC) for pleural fluid/blood (AUCPF/AUCblood) ratio=1.37) followed by levofloxacin (ratio=1.13). The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h). With moxifloxacin, the peak pleural fluid concentration (Cmax,PF) was 2.77 microg.mL(-1) and occurred at a time to maximum pleural fluid concentration (Tmax,PF) of 6 h after infusion and decreased thereafter. The peak blood concentration (Cmax,blood) was 4.81 microg.mL(-1) at 1 h after administration. With levofloxacin, the peak pleural fluid level (Cmax,PF=1.39 microg.mL(-1)) occurred at 6 h (Tmax,PF=6 h) after infusion. The Cmax,blood was 1.88 microg.mL(-1) at 1 h after administration. In conclusion, differences were found in the degree of penetration of the two quinolones into infected pleural fluid in rabbits. The clinical significance of these differences is unknown. More studies are needed to evaluate the pharmacokinetic parameters in the pleural space in humans.

The effect of environmental pollution on the respiratory system of lignite miners: a diachronic study.

BACKGROUND: It is not known whether working in surface lignite mines can cause x-ray lesions or disorders of respiratory function. OBJECTIVES: The aim of the study was to investigate the diachronic impact of environmental pollution on the respiratory system of lignite miners at mines in Eordea, Greece. METHODS: Cases of 199 workers (Group A) residing permanently in the Eordea valley and 151 (Group B) living outside the Eordea valley were studied during Phase I and then re-examined after three years (Phase II). These cases were compared to those of 71 office workers living in Eordea valley (Group C) and to 96 living in Grevena, a region without pollution (Group D). The study included the completion of the MRC questionnaire for the detection of respiratory diseases, pulmonary function tests, measurement of diffusion capacity, otorhinolaryngologic examination, rhinomanonetry as well as chest and paranasal cavity X-rays. RESULTS: Chronic bronchitis was reported by 26.8%, 24.8%, 17.9% and 10.6% respectively of the subjects of groups A, B, C and D according to the answers of the questionnaire (p<0.001). The spirometry and diffusion capacity findings presented no considerable differences either in the 4 groups or between phases I and II of the study. The main problems were detected in the upper airways. A very high prevalence of severe nasal obstruction (73%, 71.2%, 55.7% and 19.3% in Groups A, B, C and D respectively) was detected. Furthermore, a high percentage of atrophic rhinitis (14%) was detected both among workers (Groups A and B) and subjects living in the Eordea valley who participated as controls (Group C). From the X-rays, hypertrophy of nasal turbinates-cartilage and polyposis was observed as follows: Group A: 53.9%, Group B: 48.1%, Group C: 46.5% and Group D: 20.3% (p<0.001). The findings related to the upper respiratory system may be due to excessive pollution by airborne particles (fly ash) pollution in the region and particularly to chromium, nickel, cobalt and lead found at high concentration levels in airborne dust. A marked association between the total air-flow in the nose and the mid-expiratory flow (p<0.01) was detected. CONCLUSIONS: We conclude that subjects working in lignite mines under conditions of excessive pollution by airborne contaminants have a high prevalence of atrophic rhinitis and, in addition to other standard examinations, should undergo rhinomanometry testing and X-ray imaging of the paranasal cavities.

Massive bilateral pleural effusion as the only first presentation of systemic lupus erythematosus.

A rare case of systemic lupus erythematosus (SLE), with massive bilateral pleural effusions as the first manifestation, is described. The patient was a previously healthy 20-year-old soldier. Initial investigations were unrevealing, but after 3 months the patient developed the full-blown syndrome. He responded well to corticosteroids and cyclophosphamide with resolution of the pleural effusions and improvement of the clinical picture. SLE should always be considered in cases of massive pleural effusions, even in the absence of other overt stigmata of the disease.