PURPOSE: Cystic fibrosis (CF) is a progressive disease which causes a continuous decline in lung capacity with age. Our study aimed to investigate the age-dependent deterioration in lung function and the effects of treatment with Fenretinide formulation (LAU-7b) in Cftr knockout (KO) mice. METHODS: Non-invasive whole-body plethysmography (WBP) was done to measure the baseline lung functions of KO and wild-type (WT) mice at the ages of 2 and 4 months. Mice were then treated for 21 days with PBS or 10 mg/kg/day LAU-7b initiated at 4 and 7 months. Standard airway resistance measurements, haematoxylin and eosin staining, and analysis of lipids, and markers of oxidation were performed. RESULTS: The 4- and 7-month-old KO mice had significantly higher lung enhanced pause (Penh) and resistance values than age-matched WT mice and 2-month-old KO mice. Likewise, analysis of ceramides showed that PBS-treated mice had higher levels of long-chain ceramides (LCCs; C14-C18) and lower levels of very-long-chain ceramides (VLCCs; C24-C26) compared to LAU-7b-treated mice. Cftr KO mice displayed markedly greater inflammatory cell infiltration and epithelial hyperplasia at the ages of 2, 4, and 7 months compared to WT. LAU-7b treatment significantly diminished this cellular infiltration and epithelial hyperplasia compared to PBS-treated mice. CONCLUSION: Our results demonstrate a progressive age-dependent decline in lung function in Cftr KO mice. Treatment with LAU-7b corrects the lipid imbalance observed in the aging KO and WT mice and, more importantly, inhibits the age-dependent deterioration in lung physiology and histopathology.

• Klíčová slova
• Airways inflammation, Ceramide imbalance, Cftr knockout mice, Cystic fibrosis, Fatty acids, LAU-7b,
• MeSH
• ceramidy metabolismus   MeSH
• cystická fibróza metabolismus   patofyziologie   MeSH
• mastné kyseliny metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• pletysmografie MeSH
• plíce patofyziologie   MeSH
• progrese nemoci MeSH
• rezistence dýchacích cest fyziologie   MeSH
• stárnutí * MeSH
• věkové faktory MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ceramidy MeSH
• mastné kyseliny MeSH

Recent research showed group B patients express higher mortality compared to group C patients when GOLD A-D grouping is used. We aimed to compare the prognostic accuracy of three GOLD classification systems, I-IV ("pre-2011"), A-D ("2011-2016") and A-D ("2017-present") in relation to mortality, exacerbation risk, quality of life (QoL) assessment and specific treatments use in a real-life COPD cohort. We used the data of 720 patients from the Czech Multicenter Research Database of COPD. Four-year mortality and time-to-exacerbation using the GOLD "pre-2011", "2011-2016" and "2017-present" classification schemes were assessed. Moreover, distribution of specific treatments use and QoL measures were analyzed. The GOLD I-IV classification system showed gradual increase in 4-year mortality across the stages (GOLD II 18.8%, III 28.5%, IV 38.7%) (p = 0.001). Using the A-D "2011-2016" classification scheme, group C patients had lower mortality (16.7%) than group B (18.7%) (p = 0.009). The A-D "2017-present" classification showed higher mortality in group B (25.5%) compared to group C (20%) (p = 0.05). For additional outcomes, the GOLD I-IV scheme showed highest match between the calculated 4-year exacerbation risk and QoL measures and GOLD stage/grouping. In terms of specific treatment distributions, various patterns for each GOLD classification system were observed with best match of GOLD "2017-present" system to the layout of GOLD groups and categories. We conclude the GOLD I-IV classification system had the highest accuracy related to mortality, QoL measures and exacerbation risk prediction, while the A-D "2017-present" scheme was most accurate within severity of symptoms prediction reflected also by more frequent specific treatments use.

• Klíčová slova
• COPD, GOLD classification, Mortality, Prognosis,
• MeSH
• časové faktory MeSH
• chronická obstrukční plicní nemoc klasifikace   diagnóza   mortalita   terapie   MeSH
• databáze faktografické MeSH
• hodnocení rizik MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• metody pro podporu rozhodování * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• zdravotní stav MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH