[Longterm treatment of COPD with theophylline--still a valuable option?]. / Theophyllin in der Langzeittherapie der COPD--immer noch aktuell?

In the last decade the interest of pneumologists and therapeutic research has been focused on COPD. The increasing morbidity and mortality world wide and the important socio-economic impact challenged to improve the therapeutic options. New indications like LABA and newly introduced drugs like tiotropium may help to ameliorate symptoms, ICS potentially help to protect against exacerbations and to suppress components of the inflammatory process even in COPD. A reappraisal of the place of theophylline in the stepwise approach to treat these patients seems to be useful. This report reviews its effects as bronchodilator and the well documented additive effects in combination with betaadrenergics and anticholinergics. Further desirable actions of theophylline on the sensation of dyspnoea and on exercise capacity, on respiratory muscle function and on the cardiovascular performance are discussed but no definite conclusions can be made about the clinical utility of these effects. Given that patients are carefully selected in terms of benefit and side effects theophylline may remain a valuable therapeutic option.

Extrinsic allergic alveolitis in domestic environments (Domestic allergic alveolitis) caused by mouldy tapestry

Extrinsic allergic alveolitis often occures as bird fancier's lung or is caused by occupational treatment with antigenic materials. In housing environments antigens of allergic alveolitis are also found, especially mould fungi. lf a source of antigens is absent in the anamnesis and the clinical picture as well as the clinical findings are ambiguous, the diagnosis of extrinsic allergic alveolits is delayed or unobtained. The following example shows that in spite of a detailed allergic anamnesis the source of antigens may remain occult and only an inspection of the dwelling rooms leads to an elucidation. - A sixty-one year old non-smoking women was twice admitted to hospital with a temperature of more than 39 degrees C, intense dyspnea on exertion and a strong dry cough under the persumed diagnosis pneumonia. The laboratory values showed nonspecific signs of inflammation, the blood gas analysis was changed to a heavy hypoxemia (pO subset2 49.2 mmHg) and in the chest x-ray there were seen miliary and partly reticular alterations. The chest computed tomography showed extensive densities in both upper and lower parts of the lungs and the pulmonary function test corresponded with a low-grade to middle-grade restriction (VC subsetin = 67%, TLC = 69%). A high dose of corticosteroids produced an improvement of the radiological findings and of the pulmonary function. Also the specialized diagnostic in a hospital for pulmonary diseases yielded no new knowledge, and an interstitial pneumonia was diagnosed. Only the new formation of an acute pneumonic clinical picture on the day of returning to the patients own habitation suggested a noxious substance in the domestic environment. The inspection of the rooms finally showed the source of antigen to be from a condensation water soaked, moulded tapestry on the embrasure of a small unopenable window in the bedroom just on the head of the bed. The nutritive mediums left in the rooms furnished evidence of the mould-species Penicillium, Cladosporium and Botrytis, in the bedroom however mostly Penicillium. The RAST of specific IgG proved a positive result of all three mould species (Penicillium sp. 1 : 100, Cladosporium sp. 1 : 200 and Botrytis sp. 1 : 200). The diagnosis of an extrinsic allergic alveolitis caused by mould was confirmed by a controlled re-exposure test, which promptly gave rise to a relapse and forced the patient to change habitation with the result of no further ailments. - Characteristic for the extrinsic allergic alveolitis in the described case is the inefficiency of antibiotic therapy, the immediate recovery by corticosteroids and furthermore the outbreak of relapses caused by re-exposure. If the source of antigens is unclear, the inspection of the habitation by an experienced allergologist may lead to success.

Therapeutic equivalence and acceptability of two multidose powder inhalers in the treatment of asthma.

BACKGROUND: Problems in using conventional inhalation aerosols, in addition to environmental reasons, have driven development of the dry powder inhalers. OBJECTIVE: To compare therapeutic equivalence and acceptability of two dry powder inhalers, Easyhaler (EH) and Diskhaler (DH), in the delivery of beclomethasone dipropionate (BDP) in the treatment of asthma. METHODS: Adult asthmatics (n = 185), previously treated with inhaled steroids, were recruited in this open parallel-group study. After a run-in period of 2 weeks during which the patients inhaled 800 microg/day of BDP via DH, the patients were randomly allocated into three groups: EH 200 group (62 patients) using EH 200 microg/dose inhaler (1 inhalation q.i.d.), EH 400 group (62 patients) using EH 400 microg/dose inhaler (1 inhalation b.i.d.), and DH group (61 patients) using DH 200 microg/dose inhaler (1 inhalation q.i.d.) for 12 weeks. The primary outcome variables were PEF and FEV(1). RESULTS: The 95% CI for treatment difference in morning PEF between the EH 200 and DH groups was -16 to 23 litres/min and between the EH 400 and DH groups -18 to 21 litres/min. There was an increase in the morning PEF of 13 litres/min (p < 0.05) in the EH 200 group, and 9 and 11 litres/min in the DH and EH 400 groups. No differences between the groups were seen in the lung function parameters, in the symptom scores, in the use of rescue medication or in the incidence of adverse events. The treatments had no effects on morning cortisol levels. The patients in the EH groups compared the inhalers by using an 11-item questionnaire. In 8 questions the majority of the patients rated EH superior to DH. CONCLUSION: The tested inhalers were therapeutically equal. However, based on the acceptability data, the EH was better accepted by the patients than DH.

[Theophylline--past present and future]. / Theophyllin--Rückblick, Standortbestimmung und Ausblick.

Since its discovery as component of the tea leaf by Albert Kossel in 1888, the history of theophylline (CAS 58-55-9) has been a long and successful one. At the turn of the century, theophylline became less expensive due to chemical synthesis and was primarily used as diuretic in subsequent years. It was Samuel Hirsch who discovered the bronchospasmolytic effect of theophylline in 1992, however, despite this pioneering discovery theophylline continued to be used primarily as diuretic and cardiac remedy. Even when in 1936 the favourable effect of theophylline in the asthmatic state had been highlighted, this finding hardly propagated the use of this drug. Only after the pharmacokinetics and metabolism of theophylline had been elucidated and sustained release preparations had been developed in the 1970s did the substance finally experience a boost. Aside from the known relaxation of the smooth bronchial muscles, studies performed on theophylline revealed an increase in mucociliar clearance and an improvement in diaphragmatic contraction. A dose-effect relationship was described which allowed for the first time to optimise theophylline serum concentrations. In the 1980s it has become generally accepted that the pathogenesis of asthma is based on a chronic inflammatory reaction and that bronchoconstriction is the consequence rather than the cause of this disease. The unique role of theophylline both as reliever of the symptoms and as controller of the underlying asthmatic disease is reflected in the current discussion on a possible inclusion of theophylline in the list of basic therapeutic agents for the treatment of asthma.