Kronik teofilin tedavisinin hafif atopik astmalılarda metakoline hava yolu cevaplılığı üzerine etkisi

Bronkodilatör olan teofilinin immünmodülatör ve antiinflamatuvar özellikleri gösterilmiştir. Antiinflamatuvar mekanizmalar ile hava yolu aşırı cevaplılığı üzerine etkileri de araştırılmaktadır. Çalışmamızda, kronik teofilin tedavisinin (6 hafta süre ile, yavaş salınımlı, günde tek doz, 300 mg teofilin anhidr) inhale metakoline hava yolu duyarlılığı (PC20: Sensitivite) ve hava yolu reaktivitesi (eğim) değerlendirilerek hava yolu cevaplılığı üzerine etkileri araştırıldı. Sadece beta-2 agonist ilaçlara ihtiyaç duyan, yeni tanılanmış 24 hafif atopik astmalı çalışmaya alındı. Olgular, teofilin (n= 12, yaş ortalaması 30.75 ± 2.49 yıl) ve plasebo (n= 12, yaş ortalama: 34.25 ± 3.96 yıl) olan iki gruba ayrıldı. Tedavi başlangıcı (T0), tedavinin 4. günü (T1) ve 6 hafta sonunda (T2), FEV1, FEV1'de %20'lik düşüşe neden olan metakolin provokatif konsantrasyonu (PC20: Sensitivite), metakolin doz-yanıt eğrisi, reaktivite (eğim); tedavi öncesi ve 6. hafta sonunda periferik kan (PK) eozinofilisi, serum eozinofilik katyonik protein (ECP) ve serum total IgE düzeyleri değerlendirildi. Altı haftalık tedavi sonunda (serum teofilin düzeyi ortalama: 6.83 ± 0.42 µg/mL) her iki grupta ECP, total IgE düzeyleri ve PK eozinofil düzeylerinde farklılık saptanmazken, teofilin grubunda başlangıç PC20 metakolin değeri ile tedavinin 4. günü (p= 0.011) ve 6. haftasında (p= 0.012) PC20 metakolin değerleri arasında anlamlı düzelme görüldü. Teofilin tedavisinin 4. günü ve 6. haftası sonunda metakolin doz-yanıt eğrisinde hesaplanan eğimin (reaktivite) anlamlı azaldığı (sırasıyla; eğim T0-T1 p= 0.017, eğim T0-T2 p= 0.005) ve doz-yanıt eğrisinde sağa kayma olduğu belirlendi. Sonuçta, düşük doz kronik teofilin tedavisinin metakoline hava yolu duyarlılığında düzelme yanında, reaktiviteyi de azalttığı ve tedavinin 4. gününde elde edilen metakolin provokasyonuna karşı bronkoprotektif etkinin, tedavinin 6. haftası sonunda korunduğu gösterildi.

The effect of chronic treatment with theophylline on airway responsiveness in mild atopic asthmatic subjects

Theophylline is known as a bronchodilator drug. Recently, it has been shown that it has immunomodulatory and anti-inflammatory properties. Its effects on bronchial hyperresponsiveness by means of anti-inflammatory mechanisms are also studied. In this study, we investigated the effect of chronic treatment with theophylline (slow-release preperation, theophylline anhidr-diffutab retard system, 300 mg/day, for 6 weeks) on airway responsiveness which can be assessed by changes in airway sensitivity (PC20) and reactivity (slope) to inhaled methacholine. 24 mild atopic asthmatic subjects who were newly diagnosed and treated with beta-2 agonists entered the study. 12 subjects received theophylline and 12 subjects received placebo. The patients had a mean age of 30.75 ± 2.49 years and 34.25 ± 3.96 years in theophylline and placebo groups, respectively. At the beginning of treatment period (T0), on the 4th day (T1) and at the end of 6 weeks (T2), baseline FEV1, the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20: Sensitivity), reactivity (slope), methacholine dose-response curves were evaluated. In peripheral blood samples obtained before and after 6 weeks of treatment, percentage of eosinophils, total IgE and eosinophilic cationic protein (ECP) levels were measured. After 6 weeks of treatment (serum theophylline level; 6.83 ± 0.42 µg/mL) there was no significant change in the number of eosinophils, serum total IgE and ECP levels between theophylline and placebo groups. In theophylline group there was a significant increase in mean PC20 values on the 4th day and at the end of 6th week respectively; p= 0.011, p= 0.012. Slope (reactivity) was calculated from methacholine dose-response curves. A significant decrease was observed in mean slope values on the 4th day and at the end of 6 weeks of theophylline treatment, respectively; slope T0-T1 p= 0.017, slope T0-T2 p= 0.005. There was also a shift of the dose-response curve to the right. In conclusion, chronic treatment with theophylline improves the reactivity, as well as the sensitivity of the airways to methacholine and it preserves its bronchoprotective effect that was achieved on the 4th day, still at the end of 6th week.

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