Fonksiyonel karın ağrısı olan çocuklarda sinbiyotiklerin etkinliği ve immün sistem üzerine olan etkisi
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Date
2015
Authors
Otuzbir, H. Ayşegül
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Fonksiyonel gastrointestinal hastalıklar (FGİH), 2006 yılında son kabul edilen Roma III kriterlerine göre, yapısal veya biyokimyasal anormal bulguların eşlik etmediği, açıklanamayan, değişen derecelerde kronik veya tekrarlayıcı gastrointestinal semptomlar olarak belirlenmiştir. Tedavinin öncelikli amacı ağrının tamamen eradike edilmesi değil mümkün olduğunca kontrol altına alınarak çocuğun düzenli okul devamlılığının, normal uykusunun ve ders dışı aktivitelere katılımının sağlanmasıdır. Karın ağrısıyla ilişkili FGİH'ların tedavisine ilişkin kanıtlar çok sınırlıdır ve bu konuda çok az plasebo kontrollü çalışma mevcuttur. İntestinal mikrobiyotanın, gastrointestinal sistem epitelinin matürasyonu, mukozal bariyeri sağlama, viseral hipersensitivite, intestinal immün cevap, intestinal motilite üzerine olan olumlu etkileri göz önünde bulundurulduğunda FGİH'ların patogenezinde önemli bir rol oynadığı düşünülmektedir. Bu aşamada probiyotik, prebiyotik ve sinbiyotiklerin intestinal mikrobiyota ve disbiyozis üzerine önemli rolü bulunmaktadır. Fonksiyonel karın ağrısı ve fonksiyonel dispepsi gibi çocukluk çağında çok sık karşılaşılan rekürren karın ağrısı nedenleri ile ilgili olarak, probiyotik ve sinbiyotiklerin tedavideki etkinliği, serum pro-inflamatuar ve anti-inflamatuar sitokin düzeyleri üzerine etkisini araştırmayı amaçladık. Uludağ Üniversitesi Tıp Fakültesi, Çocuk Gastroenteroloji, Hepatoloji ve Beslenme polikliniğine Ocak 2015-Mayıs 2015 tarihleri arasında tekrarlayan karın ağrısı ile başvurup Roma III kriterlerine göre fonksiyonel karın ağrısı fonksiyonel dispepsi tanısı alan hastalar çalışmaya alındı. Çalışma randomize çift kör plasebo kontrollü olarak yürütüldü, olgular poliklinik ilk başvuru zamanlarına göre sıra ile denek grubu (grup 1, n=39) ve kontrol grubu (grup 2, n=41) olarak iki gruba ayrıldı. Çalışmanın başında ve sonunda ağrı şiddeti, ağrı sıklığı ve okul devamsızlık, okula devamsızlık gün sayısı, günlük aktivitede kısıtlanma gibi günlük yaşamı etkileyen faktörler ile birlikte pro-inflamatuvar sitokinler; TNF α, IFN γ ve anti-inflamatuvar sitokinler; IL-10, IL-13, regülatuar sitokin; TGF β serum düzeyleri değerlendirildi. Tedavi sonunda; tedavi başarısı (ağrı olmaması), şikayetlerde azalma oranı ayrıca değerlendirildi. SPSS 16.0 for Windows istatistik programı kullanarak değişkenler arasındaki ilişkiler incelendi. Fonksiyonel karın ağrısı ve fonksiyonel dispepsisi olan 80 hasta alındı. Hastaların ortalama yaşları 11.48±3.86 (ort ±SD) yaş idi. Çalışmaya alınan hastaların 46'sı kız (%57.5), 34'ü erkek (%42.5) idi. Her iki grup, başvuru şikayetleri, ağrı sıklığı, ağrı şiddeti, ağrı süresi ve ağrı lokalizasyonu açısından karşılaştırıldı ve istatistiksel fark saptanmadı (p>0.05). Tedavi öncesi IL-13, IL-10, IFN γ, TGF β, TNF α serum düzeyleri gruplar arasında anlamlı farklılık saptanmadı (p>0.05). 8 haftalık tedavi sonrası tam düzelme (%100), grup 1' de n=25 (%58.1), grup 2'de n=18 (%41.9) olarak grup 1'de daha fazla bulundu ancak istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05). Şikayetlerde azalma oranı grup 1'de (80.64±34.47), grup 2'ye (63.78±42.24) göre daha fazla idi, sınırda istatistiksel anlamlı farklılık saptandı (p=0.05). Tedavi sonrası IL-13, IL-10, IFN γ, TGF β, TNF α serum düzeyleri karşılaştırıldığında gruplar arasında anlamlı farklılık saptanmadı (p>0.05). Çalışmamızda çocuklarda tekrarlayan karın ağrısının önemli bir nedeni olan karın ağrısı ile ilişkili FGİH'lar ve alt grupları olan fonksiyonel karın ağrısı ve fonksiyonel dispepsi incelendi. Patofizyolojisinde genetik, çevresel, ailesel, psikososyal, gastrointestinal motilite, bozulmuş beyin-barsak aksı, mukozal immündisregülasyon, disbiyozis, mukus sekresyon ve bariyer fonksiyon bozukluğu gibi birçok faktörün rol oynadığı bu karışık hastalık grubunda çalışmamızda probiyotiklerin tedavideki etkinliğini ve immün sisteme olan etkisini göstermeye çalıştık. Probiyotiklerin FGİH'larda hangi dozda, hangi probiyotik türü ile ne kadar süre verilmesi gerektiği, sitokin düzeylerine etkisi konusunda yapılacak diğer çalışmalara kaynak oluşturacağını düşünmekteyiz.
Rome III criteria updated in 2006 identify functional gastrointestinal diseases (FGD) as chronic, recurrent and unexplained gastrointestinal symptoms without any abnormal morphologic or biochemical findings. Primary goal of treatment is not complete resolution of pain; but controlling it as much as possible to allow the children to maintain regular school attendance, extra-curricular activities and a healthy sleep pattern. Data about the treatment of FGDs associated with abdominal pain is limited; and there are few placebo controlled studies. Intestinal microbiota has important effects on maturation of gastrointestinal epithelia, formation of mucosal barrier, visceral hypersensitivity, intestinal immune response and motility; and considered to play a major role in pathogenesis of FGDs. Probiotics, prebiotics and synbiotics has substantial effects on intestinal microbiota and dysbiosis. Regarding the causes of functional abdominal pain and dyspepsia in children, we aim to investigate the efficacy of probiotics and synbiotics in treatment and their effects on levels of pro and anti-inflammatory cytokines in serum. Patients presented with recurrent abdominal pain and diagnosed as functional abdominal pain and functional dyspepsia (Rome III Criteria) in Uludağ University Medical Faculty Pediatric Gastroenterology, Hepatology and Nutrition department between January 2015 and May 2015 are enrolled in the study. Study was designed and conducted as double blind and placebo controlled. Cases were divided into two groups as subject group (group 1, n=39) and control group (group 2, n=41) according to their time of admittance. Pain intensity, frequency, number of days of school nonattendance, limitation of daily activities and serum levels proinflammatory (TNF α, IFN γ) and anti-inflammatory (IL-10, TGF β, IL-13) cytokines were evaluated both at the beginning and the end of study. Treatment success (resolution of pain) and rate of reduction of complaints were also evaluated following treatment. Associations between variables were evaluated using statistical program, 'SPSS 16.0 for Windows'. Eighty patients with functional abdominal pain and dyspepsia were enrolled. Mean age was 11.48±3.86 (mean ±SD) years. Forty six of patients (%57.5) were girls and 34 (%42.5) were boys. We found no statistical difference in presenting symptoms, pain intensity and frequency, location and duration of pain between groups. (p>0.05). Pre-treatment levels of serum IL-13, IL-10, IFN γ, TGF β, TNF α were similar (p>0.05). Complete resolution after 8 weeks of treatment was achieved in 25 patients (%58.1) in group 1and 18 patients (%41.9) in group 2, difference was not statistically significant. (p>0.05). Rate of reduction in complaints was higher in group 1 (80.64±34.47) than group 2 (63.78±42.24); difference was slightly significant (p=0.05). Post- treatment serum levels of IL-13, IL-10, IFN γ, TGF β, TNF α were similar between groups (p>0.05). We investigated FGD; functional abdominal pain and dyspepsia; as major causes of recurrent abdominal pain in children. Pathophysiology of FGDs includes genetic, environmental, familial, psychosocial factors as well as gastrointestinal motility, impaired brain-gut axis, dysregulation of mucosal immunity, dysbiosis, dysfunction of mucus secretion and barrier formation. We tried to evaluate the efficacy and immunologic effects of probiotics in this complex disease group. We believe our study can lead to other studies investigating dose, duration and choice of probiotics in FGDs; and also their effect on cytokine levels.
Rome III criteria updated in 2006 identify functional gastrointestinal diseases (FGD) as chronic, recurrent and unexplained gastrointestinal symptoms without any abnormal morphologic or biochemical findings. Primary goal of treatment is not complete resolution of pain; but controlling it as much as possible to allow the children to maintain regular school attendance, extra-curricular activities and a healthy sleep pattern. Data about the treatment of FGDs associated with abdominal pain is limited; and there are few placebo controlled studies. Intestinal microbiota has important effects on maturation of gastrointestinal epithelia, formation of mucosal barrier, visceral hypersensitivity, intestinal immune response and motility; and considered to play a major role in pathogenesis of FGDs. Probiotics, prebiotics and synbiotics has substantial effects on intestinal microbiota and dysbiosis. Regarding the causes of functional abdominal pain and dyspepsia in children, we aim to investigate the efficacy of probiotics and synbiotics in treatment and their effects on levels of pro and anti-inflammatory cytokines in serum. Patients presented with recurrent abdominal pain and diagnosed as functional abdominal pain and functional dyspepsia (Rome III Criteria) in Uludağ University Medical Faculty Pediatric Gastroenterology, Hepatology and Nutrition department between January 2015 and May 2015 are enrolled in the study. Study was designed and conducted as double blind and placebo controlled. Cases were divided into two groups as subject group (group 1, n=39) and control group (group 2, n=41) according to their time of admittance. Pain intensity, frequency, number of days of school nonattendance, limitation of daily activities and serum levels proinflammatory (TNF α, IFN γ) and anti-inflammatory (IL-10, TGF β, IL-13) cytokines were evaluated both at the beginning and the end of study. Treatment success (resolution of pain) and rate of reduction of complaints were also evaluated following treatment. Associations between variables were evaluated using statistical program, 'SPSS 16.0 for Windows'. Eighty patients with functional abdominal pain and dyspepsia were enrolled. Mean age was 11.48±3.86 (mean ±SD) years. Forty six of patients (%57.5) were girls and 34 (%42.5) were boys. We found no statistical difference in presenting symptoms, pain intensity and frequency, location and duration of pain between groups. (p>0.05). Pre-treatment levels of serum IL-13, IL-10, IFN γ, TGF β, TNF α were similar (p>0.05). Complete resolution after 8 weeks of treatment was achieved in 25 patients (%58.1) in group 1and 18 patients (%41.9) in group 2, difference was not statistically significant. (p>0.05). Rate of reduction in complaints was higher in group 1 (80.64±34.47) than group 2 (63.78±42.24); difference was slightly significant (p=0.05). Post- treatment serum levels of IL-13, IL-10, IFN γ, TGF β, TNF α were similar between groups (p>0.05). We investigated FGD; functional abdominal pain and dyspepsia; as major causes of recurrent abdominal pain in children. Pathophysiology of FGDs includes genetic, environmental, familial, psychosocial factors as well as gastrointestinal motility, impaired brain-gut axis, dysregulation of mucosal immunity, dysbiosis, dysfunction of mucus secretion and barrier formation. We tried to evaluate the efficacy and immunologic effects of probiotics in this complex disease group. We believe our study can lead to other studies investigating dose, duration and choice of probiotics in FGDs; and also their effect on cytokine levels.
Description
Keywords
Fonksiyonel gastrointestnal hastalıklar, Sinbiyotikler, Sitokinler, Functional gastrointestinal diseases, Synbiotcs, Cytokines
Citation
Otuzbir, H. A. (2015). Fonksiyonel karın ağrısı olan çocuklarda sinbiyotiklerin etkinliği ve immün sistem üzerine olan etkisi. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.