New Findings
What is the central question of this study?
How does oxygen therapy influence cerebral blood flow, cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary ...disease patients?
What is the main finding and its importance?
Oxygen therapy improves cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients. This improvement in cerebral oxygen delivery and neurovascular function might provide a physiological link between oxygen therapy and a reduced risk of cerebrovascular disease (e.g. stroke, mild cognitive impairment and dementia) in chronic obstructive pulmonary disease.
We investigated the role of hypoxaemia in cerebral blood flow (CBF), oxygen delivery (CDO2) and neurovascular coupling (coupling of CBF to neural activity; NVC) in hypoxaemic chronic obstructive pulmonary disease (COPD) patients (n = 14). Resting CBF (duplex ultrasound), peripheral oxyhaemoglobin saturation (SpO2; pulse‐oximetry) and NVC (transcranial Doppler) were assessed before and after a 20 min wash‐in of supplemental oxygen (∼3 l min−1). The peripheral oxyhaemoglobin saturation increased from 91.0 ± 3.3 to 97.4 ± 3.0% (P < 0.01), whereas CBF was unaltered (593.0 ± 162.8 versus 590.1 ± 138.5 ml min−1; P = 0.91) with supplemental O2. In contrast, both CDO2 (98.1 ± 25.7 versus 108.7 ± 28.4 ml dl−1; P = 0.02) and NVC were improved. Specifically, the posterior cerebral artery cerebrovascular conductance was increased to a greater extent after O2 normalization (+40%, from 20.4 ± 9.9 to 28.0 ± 10.4% increase in conductance; P = 0.04), whereas the posterior cerebral artery cerebrovascular resistance decreased to a greater extent during O2 normalization (+22%, from −16.7 ± 7.3 to −21.4 ± 6.6% decrease in resistance; P = 0.04). The cerebral vasculature of COPD patients appears insensitive to oxygen, because CBF was unaltered in response to O2 supplementation leading to improved CDO2. In patients, the improvements in CDO2 and neurovascular function with supplemental O2 may underlie the cognitive benefits associated with O2 therapy.
Astma je najčešća plućna bolest, iako s manjim utjecajem na zbroj izgubljenih godina života zbog preuranjene smrtnosti i godina proživljenih s invaliditetom nego neke druge plućne bolesti, kao što je ...kronična opstruktivna plućna bolest. Budući da se radi o bolesti s velikim javnozdravstvenim utjecajem na radnu sposobnost i kvalitetu života oboljelih, kao i s potrošnjom značajnih zdravstvenih i financijskih resursa, potrebno je primijeniti
kvalitetno i standardizirano liječenje. Osnova liječenja astme – primjena temeljnoga protuupalnog lijeka s najmanjom dozom koja može održati dobru kontrolu – nije se značajno promijenila u odnosu na posljednje hrvatske smjernice za dijagnostiku i liječenje astme u odraslih, objavljene prije petnaestak godina. Međutim, u međuvremenu su se u globalnoj strategiji za upravljanje i prevenciju astme dogodile značajne promjene u stavu
prema kratkodjelujućem bronhodilatatoru salbutamolu, gdje se on više ne primjenjuje samostalno u akutnom bronhospazmu ili pri pojavi tegoba, bez inhalacijskog glukokortikoida. Također, značajan je napredak postignut u biološkoj terapiji teške astme, prepoznat je značaj izrade osobnog plana liječenja astme, kao i pojava novih mogućnosti liječenja (fiksna trojna terapija), što je uključeno u nove hrvatske smjernice za liječenje astme.
High ERCC1 expression is thought to be related with resistance to chemotherapy based on platinum. The aim of this study was to present our institutional observations regarding to the association of ...ERCC1 and overall survival (OS) of the lung adenocarcinoma patients who received chemotherapy based on platinum.
A total of 253 lung adenocarcinoma patients in all TNM stages were retrospectively investigated. The diagnosis was based on small biopsy samples obtained during bronchoscopy. Depending on the TNM stage of the disease and clinical condition, patients received only the chemotherapy based on platinum, or in combination with radiotherapy or surgery. Tissue sample for ERCC1 immunohistochemical analysis was sufficient in 129 patients. Low from high ERCC1 expression was separated by the semi-quantitative H-score median.
High ERCC1 expression was found in 47.3% patients, and was correlated with higher TNM (p = 0.021), tumor enlargement (p = 0.002), positive lymph nodes (p = 0.001), positive distant metastasis (p = 0.005), and higher relative risk of death (p < 0.001). Furthermore, significance association was observed for low ERCC1 expression and better performance status (ECOG) (p = 0.023). Longer OS was strongly associated with a low ERCC1 expression, not only in the group of patients in TNM stage I-III, who were treated with combination of chemotherapy with surgery or radiotherapy (p = 0.002), but also in the group of patients in TNM stage IV who received only chemotherapy based on platinum (p < 0.001), compared with the patients in the same TNM stage and high ERCC1 expression.
ERCC1 expression in lung adenocarcinoma is a useful prognostic marker and moreover, a useful predictive marker in patients receiving chemotherapy based on platinum in all stages of the disease.
Renal sarcoidosis frequently causes granulomatous interstitial nephritis, but clinically relevant nephritis is uncommon. IgA nephropathy caused by sarcoidosis is usually associated with milder stages ...of renal dysfunction, and only one case of rapidly progressive IgAN has been reported to date. We present an interesting case of a patient with a rapidly progressive form of IgA nephropathy caused by sarcoidosis that was successfully treated.DOI: 10.52547/ijkd.7027
Pretilost i opstruktivne plućne bolesti Mladinov, Suzana; Ilak, Dino
Medicus (Zagreb, Croatia : 1992),
04/2018, Volume:
27, Issue:
1 Debljina i ...
Journal Article
Peer reviewed
Open access
Istodobni porast globalne prevalencije pretilosti, KOPB-a i astme ima važne zdravstvene i ekonomske implikacije. Pretilost je metabolički poremećaj koji se može povezati sa sustavnom upalom u KOPB-u ...i astmi. U odnosu prema bolesnicima koji su normalno uhranjeni pretili bolesnici s KOPB-om i astmom imaju više komorbiditeta, bolesnici s KOPB-om izraženiju zaduhu, manji funkcionalni kapacitet i lošiju kvalitetu života, a bolesnici s astmom češće egzacerbacije i odsutnost tipične eozinoDlne upale te slabiji odgovor na terapiju. „Paradoks pretilosti“ u KOPB-u odnosi se na dulje preživljenje pretilih osoba koje ovisi ne samo o ukupnoj tjelesnoj masi nego i o udjelu i distribuciji masti. U procesu smanjenja tjelesne mase prednost treba dati strategijama gubitka te mase s održanjem mišićne mase. U astmi razlikujemo dva fenotipa povezana s pretilošću: alergijsku astmu ranog nastupa koja se javlja u mlađoj životnoj dobi s dominantnim Th2-upalnim odgovorom (Th2-high) i komplicira se pretilošću u kasnijoj životnoj dobi te nealergijsku astmu kasnog nastupa koja se češće javlja u žena u odrasloj dobi kao komplikacija inicijalno prisutne pretilosti i obilježena je niskim intenzitetom Th2-upalnog odgovora (Th2-low). Nekoliko je načina kojima gubitak tjelesne mase pozitivno utječe na kontrolu astme: poboljšanjem mehanike prsnog koša, ublažavanjem gastroezofagealnog refluksa te sniženjem intenziteta upale.
The aims of this study were: (1) to test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with moderate-severe COPD, and (2) to test whether low flow oxygen ...administration improves endothelial function and is protective against oscillatory shear stress-induced endothelial dysfunction in patients with moderate-severe COPD. In 17 patients and 10 age-matched non-smoking control subjects we examined brachial artery flow-mediated dilation (FMD) and circulating microparticles before and after 20 minutes of experimentally-induced oscillatory shear stress. COPD patients performed this intervention a second time following a 20-minute wash in period of low flow supplemental oxygen to normalize arterial oxygen saturation. COPD patients had ~six-fold greater baseline retrograde shear rate (P < 0.05) and lower FMD (P < 0.05). The oscillatory shear stress intervention induced significant decreases in brachial artery FMD of all groups (P < 0.05). Oscillatory shear stress elevated circulating markers of endothelial cell apoptosis (CD31+/CD41b- microparticles) in COPD patients, but not age-matched controls. Supplemental oxygen administration abrogated the oscillatory shear stress-induced increase in CD31+/CD41b- microparticles, and improved FMD after accounting for the shear stress stimulus. We have demonstrated that acutely disturbed blood flow with increased retrograde shear stress further deteriorates the already impaired endothelial function with attendant endothelial apoptosis in patients with moderate-severe COPD.
Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe ...the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF.
The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors.
The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9).
EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.
Hepcidin is the main regulator of systemic iron homeostasis and its expression is modulated by iron status, hypoxia, erythroid factors and inflammation. The aim of our study was to examine a ...relationship between level of hepcidin and iron status, erythropoietic activity, hypoxia and inflammation in exacerbations and stable COPD patients. We hypothesized that hepcidin concentration is changed in COPD patients and is substantially influenced by inflammation and/or hypoxia.
The study included 40 COPD patients and 30 healthy subjects. We measured haemoglobin, serum level of hepcidin and parameters indicative for inflammation: interleukin-6 (IL-6) and C reactive protein (CRP); hypoxia: partial oxygen pressure and haemoglobin oxygen saturation; iron status: iron, total iron binding capacity (TIBC), transferring saturation and ferritin; and erythropoietic activity: soluble transferrin receptors, reticulocytes, and erythropoietin.
Hepcidin was elevated in exacerbations and in a stable phase compared to the control group and we found positive correlations of hepcidin with inflammatory markers IL-6 and CRP. Hepcidin also correlated positively with ferritin and inversely with TIBC. However, in COPD patients reticulocyte count was significantly reduced and negative correlation with hepcidin was established in exacerbation. No correlations were observed with iron, or indices of hypoxia. In the control group, positive associations were observed only with indices of iron status, positive with ferritin and negative one with TIBC.
Systemic inflammation and elevated values of IL-6 present in exacerbations and stabile COPD might be responsible for the observed increased hepcidin level.
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•Serum hepcidin level is increased in exacerbation and stable COPD.•Hepcidin correlates with IL-6 as its main regulator during inflammation.•Systemic inflammation might be principal determinant of hepcidin in COPD.
Introduction: The I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021. Aim: We aimed to measure VE ...against PCR-confirmed SARS-CoV-2 in patients ≥20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period). Methods: In both networks, 46 hospitals (13 countries) follow a similar test-negative case–control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received≥14 days before symptom onset (stratifying first booster into received<150 and≥150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition. Results: We included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29–54) for complete PSV (with last dose received≥150 days before onset), while it was 59% (95% CI: 51–66) after addition of one booster dose. The VE was 85% (95% CI: 78–89), 70% (95% CI: 61–77) and 36% (95% CI: 17–51) for those with onset 14–59 days, 60–119 days and 120–179 days after booster vaccination, respectively. Conclusions: Our results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset<120 days after first booster dose.
Patients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, ...antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry.
For this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient's past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan-Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment.
A population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths.
The majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.
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