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ID naloge: 142 Letnik: 2003 Predmet: interna medicina
PONOVLJIVOST MERITEV DUŠIKOVEGA OKSIDA V IZDIHANEM ZRAKU PRI ZDRAVIH, BOLNIKIH Z ASTMO IN KRONICNO OBSTRUKTIVNO PLJUCNO BOLEZNIJO
Avtor: Milica Lukic, Katja Mohorcic
Mentor: doc. dr. Matjaž Fležar
Izhodišce: Poglavitni obstruktivni bolezni pljuc sta astma in kronicna obstruktivna pljucna bolezen (KOPB). Pri obeh je obstrukcija posledica kronicnega vnetja v dihalnih poteh. Dušikov oksid (NO) je marker vnetja v dihalnih poteh. Koncentracija NO v izdihanem zraku se z intenzivnostjo vnetja spreminja. Predvsem eozinofilno vnetje je združeno z najvecjimi porasti izlocenega NO in pri astmi je tudi dokazano, da se izloceni NO mocno zniža, ce bolnika zdravimo z inhalacijskim protivnetnim zdravilom. Nakazujejo se možnosti, da se z meritvijo NO nadzira bolnikovo sodelovanje pri zdravljenju, služi pa tudi kot napovednik poslabšanja astme. Poznana je cela vrsta dejavnikov, ki na te meritve vplivajo in niso direktno povezani z eozinofilnim vnetjem. Standardizacija postopka meritve s sodobnimi analizatorji je torej kljucna za uvedbo te metode v vsakdanjo klinicno prakso.
Namen: S ponovljenimi meritvami izdihanega NO pri zdravih, bolnikih z astmo in bolnikih s KOPB smo statisticno opredelili ponovljivost in zanesljivost meritve NO v izdihanem zraku. Opredelili smo obmocje izmerjenih vrednosti pri dveh ponovljenih testih v štiri tedenskem razmiku ter pri parnih testih pri istih osebah pred in po obremenitvi. Izracunali smo korelacije med ponovljenimi meritvami, koeficient variacije in porazdelitev izmerjenih vrednosti.
Hipoteza: Izracun ponovljivosti meritve nam bo pri ponovljenih meritvah pokazal, kdaj bo v naših okolišcinah ponovljena meritev izven normalne variacije meritve pri zdravih, bolnikih z astmo in KOPB. Štiri tedenski razmik in telesna obremenitev ob stabilni bolezni ne bosta vplivala na ponovljivost meritve. Dolocili bomo mejo med zdravimi in bolnimi glede na koncentracijo izlocenega NO.
Metode: V raziskavo smo vkljucili 15 zdravih preiskovancev, 17 bolnikov z astmo in 14 bolnikov s KOPB. Skupina bolnikov s KOPB je bila povprecno 15 let starejša od drugih dveh skupin. Koncentracijo izdihanega NO smo merili s kemilumiscentnim analizatorjem, ki meri NO v obmocju 1 - 1000 ppb. Primerjali smo rezultate meritev pred in po telesni obremenitvi pri dveh obiskih, locenih vsaj 4 tedne. Za analizo smo uporabili neparametricne statisticne teste (Kruskal-Wallis Test, Wilcoxon Signed Ranks test in Spearmanov koeficient).
Rezultati: Porazdelitev vrednosti izdihanega NO je bila nenormalna. Standardizacija pogojev meritve in celotne metode je pokazala, da vrednosti NO nad 29 ppb izmerimo pri manj kot 5% zdravih ljudi in so zato zelo verjetno bolezenske. Meritev je bila dobro ponovljiva pri istem bolniku pred in po obremenitvi na isti dan preiskave s koeficientom variacije, ki je bil vedno pod 10%. Ugotovili pa smo slabo ponovljivost testa pri istem bolniku ob dveh razlicnih obiskih. Trije bolniki so imeli ob stabilni klinicni sliki in preiskavi pljucne funkcije signifikantno povišane vrednosti izdihanega NO.
Zakljucek: Z rezultati smo potrdili vse naše delovne hipoteze. Meritev izdihanega NO so opravili lahko prav vsi preiskovanci, ne glede na stopnjo okvare pljucne funkcije. Povišana koncentracija izdihanega NO in aktivnost eozinofilnega vnetja ne korelirajo vedno s klinicno sliko. Vrednosti NO nad 29 ppb sugerirajo nadaljevanje diagnosticnega postopka za dokaz eozinofilnega vnetja v dihalih.
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[Abstract / English version]
PONOVLJIVOST MERITEV DUŠIKOVEGA OKSIDA V IZDIHANEM ZRAKU PRI ZDRAVIH, BOLNIKIH Z ASTMO IN KRONICNO OBSTRUKTIVNO PLJUCNO BOLEZNIJO
Author: Milica Lukic, Katja Mohorcic
Mentor: doc. dr. Matjaž Fležar
Background: Asthma and chronic obstructive pulmonary disease (COPD) are major obstructive lung diseases. Both are characterized by airflow obstruction resulting from chronic inflammation in the airways. Nitric oxide (NO) is a marker of inflammation in the airways. Its concentration in exhaled air varies with the intensity of inflammation. The elevations of exhaled NO are particularly present in eosinophilic airway inflammation. It has been proved that the concentration of exhaled NO significantly decreases in patients with asthma after treatment with inhaled corticosteroids. Measurement of exhaled NO should therefore enable us to detect non-adherent individuals as well as to monitor the inflammation and predict exacerbations of asthma. Many factors have been recognized to affect the result of the measurement that have not been directly related to eosinophilic inflammation. The standardization of the measurement with new on-line analyzers, which detect extremely low concentration of exhaled NO, is essential in order to use the method in everyday clinical practice.
Aim: By repeated measurements of exhaled NO in patients with asthma, COPD and in healthy subjects we evaluated the repeatability and reliability of the measurement of exhaled NO. We determined the range of measured values by two repeated tests in four week interval as well as by paired tests in same individual before and after the exercise. We also calculated the correlation between repeated measurement, coefficient of variation and distribution of measured values.
Hypothesis: Calculation of coefficient of variation will allow us to compare the results of repeated measurements as a part of a normal variation or as a true difference between the two results in healthy subjects, patients with asthma and patients with COPD. Four week interval between the measurements and exercise will not affect the repeatability of measurement in stable disease. We will set the value of exhaled NO which separates healthy subjects from individuals with obstructive lung disease.
Methods: We included 15 healthy individuals, 17 patients with asthma and 14 patients with COPD. Expired air was analyzed by chemiluminiscent analyzer with range from 1-1000 ppb. We compared the results of the measurement at two visits in at least four week interval before and after the exercise. In order to analyze our results we used nonparametric statistical tests (Kruskal-Wallis, Wilcoxon Signed Ranks test, Spearman's coefficient).
Results: The measured values of exhaled NO were not normally distributed. Standardization of measurement conditions and the whole method indicated that the values above 29 ppb occur in less than 5% healthy individuals and are probably pathologic. The repeatability of the measurement was good (coefficient of variation did not exceed 10%) regarding the same subject before and after the exercise on one particular measuring day. On the contrary, we have discovered poor repeatability regarding the results of the same subject on two different occasions. Three patients had significantly increased values of exhaled NO despite of stable disease and normal lung function.
Conclusion: Our results confirmed our hypotheses. All the subjects regardless of the deficit in their lung function could successfully perform the measurement. The correlation between clinical status and increased absolute values of exhaled NO due to eosinophilic inflammation is not always present. Values of exhaled NO above 29 ppb suggest further diagnostic procedures to assess eosinophilic inflammation in human airways.
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