Uldis Kopeika

Decreased FOXP3 expression in small airways of smokers with COPD

CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients. A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways. Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction. To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.

Patterns of inflammatory responses in large and small airways in smokers with and without chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airway obstruction. Smoking causes persistent inflammation in lung tissue. However, differences in inflammatory responses between the large and small airways have not been systematically explored among smokers with and without COPD. Objectives: The aim of our research was to characterise the expression and localisation of NF-ĸBp65 and histone deacetylase 2 (HDAC2) as well as inflammatory cell (macrophages, lymphocytes, neutrophils) distribution in large and small airways, in nonsmokers and in smokers with and without COPD. Methods: Nineteen nonsmokers, 20 smokers with normal lung ventilation function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate NF-ĸBp65 and HDAC2 expression and identify inflammatory cells in airways. Results: COPD patients had increased NF-ĸBp65 expression compared to nonsmokers and smokers without COPD, in both large and small airways, which corresponded to increased numbers of macrophages, CD8+ T lymphocytes and neutrophils. COPD patients had more macrophages in large compared to small airways and more CD8+ T lymphocytes and neutrophils in small compared to large airways. HDAC2 expression was significantly downregulated in smokers with COPD in small compared to large airways. Conclusions: Our findings indicate a nonuniform distribution of inflammatory cells throughout the bronchial tree. However, in both smokers with and without COPD, similar patterns of inflammatory processes occur in both large and small airways. The difference between smokers with and without COPD is only quantitative.

Exhaled Air Analysis in Patients with Different Lung Diseases Using Artificial Odour Sensors

Exhaled Air Analysis in Patients with Different Lung Diseases Using Artificial Odour Sensors Sniffing breath to diagnose a disease has been practiced by doctors since ancient times. Nowadays, electronic noses are successfully used in the food, textile and perfume industry as well as for air pollution control. The aim of this study was to test whether exhaled breath analysed by an artificial nose could identify and discriminate between different lung diseases. A total of 76 individuals were tested: 25 bronchial asthma, 19 lung cancer, 10 pneumonia, 6 chronic obstructive pulmonary disease (COPD) patients and 16 healthy volunteers. Exhaled air was collected in plastic bags and immediately analysed using an electronic nose instrument (9185, Nordic Sensors AB) containing 14 different odour sensors. Multifactor logistic regression analysis was used to determine correlation between the amplitudes of sensor responses and the clinical diagnoses of patients and to calculate sensitivity and specificity of the method for each diagnosis. For diagnostics of asthma the sensitivity was found to be 84% and specificity — 86%. For lung cancer, the sensitivity was 74% and specificity, 95%; for pneumonia 90% and 98%, but for COPD, 33% and 97%, respectively. We conclude that an artificial nose is able to discriminate among different lung diseases with sufficiently good accuracy. This method may be further developed to implement it in clinical medicine for express diagnostics of acute and chronic lung diseases. Izelpas Gaisa Analīze Pacientiem Ar Dažzādām Plaušu Slimībām, Izmantojot Mākslīgos Ožas Sensorus Jau kopš seniem laikiem ārsti ostījuši pacienta elpu, lai uzstādītu slimības diagnozi. Mūsdienās ir radīts elektroniskais deguns, un to izmanto gan smaržu, gan tekstilrūpniecībā, gan lai novērtētu vides piesārņotību. Mūsu pētījuma mērķis bija noskaidrot, vai mākslīgo degunu var izmantot plaušu slimību diferenciāldiagnostikai. Pētījumā piedalījās 76 personas: 25 bronhiālās astmas slimnieki, 19 bija plaušu vēzis, 10 - pneimonija, 6 - hroniska obstruktīva plaušu slimība (HOPS), bet 16 bija veseli brīvprātīgie. Izelpas gaisu savāca plastikāta maisos un to tūlīt analizēja αr elektroniskā deguna aparātu (Nordic Sensors AB, 9185), kura sastāvā bija 14 smaržu sensori. Lai konstatētu korelāciju starp smaržas sensoru rādījumiem un konkrētām pacientu diagnozēm, kā arī lai noteiktu metodes specifiskumu un jutību, tika lietota multifaktoru logistiskās regresijas analīze. Jutība, paredzot astmas diagnozi, bija 84%, bet specifiskums - 86%. Jutība, nosakot plaušu vēzi, bija 74%, specifiskums - 95%; pneimonijai 90% un 98%, bet HOPS - attiecīgi 33% un 97%. Secinājām, ka elektroniskais deguns spēj atšķirt dažādas plaušu slimības ar pietiekamu precizitāti. Metodi varētu turpmāk attīstīt un lietot klīniskajā praksē akūtu un hronisku plaušu slimību ekspresdiagnostikai.

Comparison Of Stress Response Performing Endotracheal Intubation By Direct Laryngoscopy, Fibreoptic Intubation And Intubation By The Glidescope Laryngoscope

Comparison Of Stress Response Performing Endotracheal Intubation By Direct Laryngoscopy, Fibreoptic Intubation And Intubation By The Glidescope Laryngoscope Stress response is regulated by two primary neuroendocrine systems—the hypothalamuspituitary- adrenocortical (HPA) and sympathetic adrenomedullary (SAM) systems. Salivary alphaamylase (AA) levels can be used as an index of the SAM activity, and serum cortisol as an index of HPA activity. The aim of the study was to compare patient stress response to different intubation techniques. Sixty adult patients, ASA I-III, scheduled for elective abdominal surgery were included in this study, with median age of 54±18 years. Patients were prospectively randomly divided into three groups-intubation with a GlideScope (GS), Macintosh laringoscope (ML) and PENTAX fibreoptic bronchoscope (FB). After preoxygenation for 3 min anaesthesia was induced with fentanyl 2 mkg/kg, mivacuronium 0.2 mg/kg and propofol 2 mg/kg, injected intravenously over 20 seconds. Intubation was started 2 min after mivacuronium injection. Anaesthesia was maintained with sevoflurane 1-2 vol% and fentanyl 1 mkg/kg as needed. Intubation time (IT) was measured, blood and saliva samples were collected before and shortly after intubation. Haemodynamic response was recorded. Intubation time was statistically significantly longer in the FB group (120±65 s) versus the ML group (29±5 s) and GS group (26±9 s), P < 0.05. In the three patients groups the initial AA level was similar (54±20 KU/ml, P > 0.05). In GS patients the alpha amylase level after intubation significantly decreased (42±15 KU/ml, P < 0.05), but in ML and FB patients—significantly increased (68±24 KU/ml and 73±32 KU/ml, respectively, P < 0.05). After intubation, blood cortisol did not differ between the ML (377±181 U/ml) and GS (484±61 U/ml) patient groups, but was significantly higher (P < 0.05) in the FB group (530±79 U/ml). Both heart rate and blood pressure increased during intubation, the difference between groups was not significant. All intubations were successful, but in the FB patient group IT was significantly longer than in the ML and GS patient group. IT in the GS and FB patient groups did not statistically significantly differ. In our opinion, shorter and more confident intubations with a GlideScope produce less nociceptive stimulus and less stress to the patient. Intubations using GlideScope videolaryngoscope causes lesser stress response in comparison to intubation with a Macintosh laryngoscope or fibreoptic bronchoscope. Stresa Reakcijas Salīdzinājums Endotraheālās Intubācijas Laikā, Veicot Intubāciju AR Tiešo Laringoskopijas, Fibrobronhoskopijas UN Glidescope Metodēm Atbildi uz stresa reakciju nosaka divas neiroendokrīnas sistēmas: hipotalāma-hipofīzes-virsnieru (HPA) un simpātiski adrenālā (SAM) sistēma. Siekalu alfa-amilāze raksturo SAM aktivitāti, savukārt asins seruma kortizola līmenis - HPA aktivitāti. Darba mērķis bija salīdzināt stresa reakcijas izteiktību atkarībā no dažādām intubēšanas metodēm. Pētījumā tika iekļauti 60 pieauguši pacienti, ASA I-III, kam bija paredzēta plānveida abdomināla operācija. Vidējais pacientu vecums bija 54±18 gadi. Pacientus nejaušināti iedalījām trīs grupās un veicām intubāciju ar GlideScope laringoskopu (GS pacientu grupa), Makintoša laringoskopu (ML grupa) un PENTAX fibrooptisko bronhoskopu (FB grupa). Pēc trīs minūšu ilgas preoksigenācijas tika uzsākta anestēzija ar fentanilu 2 mkg/kg, mivacuroniju 0,2 mg/kg un Propofolu 2 mg/kg, kas tika ievadīti intravenozi 20 sekunžu laikā. Intubācija tika uzsākta pēc 2 minūtēm kopš mivakuronija injekcijas. Anestēzija tika turpināta ar sevoflurānu 1-2 vol% un fentanilu 1 mkg/kg pēc nepieciešamības. Tika noteikts intubācijas laiks, pañemti siekalu un asins paraugi pirms un īsi pēc intubācijas. Intubācijas laiks bija statistiski ticami ilgāks FB pacientu grupā (120 ± 65 sekundes) salīdzinājumā ar ML grupu (29 ± 5 s) un GS grupu (26 ± 9 s), P < 0,05. Visās trīs pacientu grupās alfa amilāzes līmenis siekalās pirms intubācijas bija vienāds (54 ± 20 KU/ml, P > 0,05). GS pacientu grupā alfa amilāzes līmenis pēc intubācijas pazeminājās (42 ± 15 KU/ml, P < 0,05), bet ML un FB pacientu grupās - statistiski ticami pieauga, attiecīgi līdz (68 ± 24 KU/ml un 73±32 KU/ml, P < 0,05). Pēc intubācijas asins seruma kortizola līmenis statistiski ticami (P < 0,05) pieauga FB pacientu grupā (530 ± 79 U/ml). Kortizola līmenis pēc intubācijas ML grupā bija (377±181 U/ml) un GS grupā (484±61 U/ml), šis pieaugums nebija statistiski ticams salīdzinājumā ar pirmsoperācijas līmeni. Gan sirdsdarbības frekvence, gan asinsspiediens pieauga intubācijas laikā, taču nenovērojām statistiski ticamu atšķirību starp pacientu grupām. Visas intubācijas bija sekmīgas, taču FB pacientu grupā intubācijas laiks bija statistiski ticami garāks salīdzinājumā ar abām pārējām pacientu grupām, kur tas neatšķirās. Mūsuprāt, ātrāka un drošāka intubācija ar GlideScope laringoskopu rada mazāku nociceptīvo elpceļu un rīkles stimulāciju, līdz ar to rada arī mazāku pacientu stresa reakciju. Intubācija ar Glidescope laringoskopu pacientiem rada mazāku stresu nekā intubācija ar Makintoša laringoskopu vai fibrooptisko bronhoskopu.