Disertasi

Peran CT Scan Toraks Kuantitatif, HIF-1α dan Faktor Klinis terhadap Kejadian Hendaya Kognitif pada Penyakit Paru Obstruktif Kronik = Role of Quantitative Thoracic CT Scan, HIF-1α, and Clinical Factors in the Incidence of Cognitive Impairment in Chronic Obstructive Pulmonary Disease.

Penyakit paru obstruktif kronik (PPOK) memiliki gejala obstruksi saluran napas progresif dan berhubungan dengan respons inflamasi. PPOK berkaitan dengan hendaya kognitif yang menurunkan kualitas hidup, ketaatan terapi yang buruk hingga kematian. Dibandingkan spirometri, CT scan toraks dianggap dapat mendeteksi lebih awal emfisema dan kelainan jalan napas. PPOK sering kali menyebabkan hipoksia sehingga meningkatkan ekspresi hypoxia-inducible factor- 1 alpha (HIF-1α). Penelitian ini bertujuan untuk menganalisis peran CT scan kuantitatif (CTK), fungsi paru, HIF-1α, dan klinis terhadap hendaya kognitif (HK) pada pasien PPOK. Studi potong lintang prospektif ini dilakukan sejak bulan Januari 2022 sampai Juni 2023 di empat rumah sakit wilayah Jakarta. Sebanyak 620 pasien yang didiagnosis PPOK dilihat data rekam medis, kuesioner Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), dan spirometri. Sejumlah 114 subjek yang masuk kriteria inklusi diperiksa dengan Montreal Cognitive Assessment versi Indonesia (MoCA-Ina) dan CTK. Mayoritas subjek adalah laki-laki (88,6%), berusia lanjut (67,5%), perokok (84,2%) dengan 42,1% perokok berat, indeks masa tubuh (IMT) normal (72,8%), derajat keparahan PPOK sesuai Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3 (37,8%), menempuh pendidikan ≥ 12 tahun (63,2%), dan hendaya kognitif (HK) (73,7%). Korelasi terkuat dengan nilai MoCA-Ina hanya pada lama pendidikan (p < 0,001). Uji chi-square menunjukkan perbedaan bermakna antara IMT (p = 0,003) dan lama pendidikan (p = 0,008) dengan HK. IMT berkorelasi lemah dengan volume ekspirasi paksa pada detik pertama persen prediksi (VEP1 pp) (p < 0,001) dan VEP1 dibandingkan kapasitas vital paru (VEP1/KVP) (p = 0,001). Percentage attenuation area (%LAA) berkorelasi lemah dengan VEP1 pp (p < 0,001) dan berkorelasi sedang dengan VEP1/KVP (p < 0,001). Analisis regresi linier menunjukkan lama pendidikan dan %LAA dapat memprediksi hendaya kognitif (R2 = 0,229; p < 0,001). Model analisis jalur menunjukkan %LAA dan lama pendidikan berpengaruh terhadap HK secara langsung dan tidak langsung melalui VEP1 pp. Disimpulkan, lama pendidikan dan %LAA berperan terhadap patomekanisme HK baik secara langsung maupun tidak langsung melalui mediator VEP1 pp.
Kata kunci: CT scan kuantitatif, hendaya kognitif, HIF-1α, MoCA-Ina, penyakit paru obstruktif kronik


Chronic obstructive pulmonary disease (COPD) has progressive airway obstruction symptoms and is associated with inflammation. COPD is associated with cognitive impairment (CI), which decreases quality of life, poor adherence to therapy, and even death. Compared to spirometry, a thoracic CT scan can detect emphysema and airway abnormalities earlier. COPD often causes hypoxia, which enhances the expression of hypoxia-inducible factor 1-alpha (HIF-1α). This study aimed to analyze the role of quantitative CT scan (QCT), lung function, HIF-1α, and clinical factors on CI in COPD patients. This prospective cross-sectional study was conducted from January 2022 to June 2023 in four hospitals in the Jakarta region. Six hundred twenty diagnosed COPD patients were screened based on medical records, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7) questionnaires, and spirometry. One hundred fourteen subjects who met the inclusion criteria underwent the Montreal Cognitive Assessment Indonesian version (MoCA-Ina) test and QCT. The majority of the subjects were male (88.6%), elderly (67.5%), smokers (84,2%), with 42.1% being heavy smokers, standard body mass index (BMI) (72.8%), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3 severity of COPD (37.8%), had ≥ 12 years of education (63.2%), and had CI (73.7%). Only education duration correlated strongly with MoCA-Ina score (p < 0.001). Chi-Square test showed significant differences between BMI (p = 0.003) and education duration (p = 0.008) with CI. BMI correlated weakly with forced expiration volume at 1-second percent predicted (FEV1 pp) (p < 0.001) and FEV1 compared with forced vital capacity (FEV1/FVC) (p = 0.001). Percentage lung attenuation area (%LAA) correlated weakly with FEV1 pp (p < 0.001) and moderately with FEV1/FVC (p < 0.001). Linear regression analysis showed that education duration and %LAA as predictors of CI (R2 = 0.299; p < 0.001). Path analysis showed that %LAA and education duration, directly and indirectly, influenced CI through FEV1 pp. In conclusion, education duration and %LAA contributed to the pathomechanism of CI either directly or indirectly through the FEV1 pp as a mediator.
Keywords: chronic obstructive pulmonary disease, cognitive impairment, HIF-1α, MoCA-Ina, quantitative CT scan