Normunds Jurka

Breath testing as a method for detecting lung cancer

Early diagnosis of lung cancer is important due to high mortality in late stages of the disease. An ideal approach for population screening could be the breath analysis, due to its non-invasiveness, simplicity and cheapness. Using sensitive methods of analysis like gas chromatography/mass spectrometry in exhaled air of cancer patients were discovered some volatile organic compounds – possible candidates for cancer markers. However, these compounds were not specific for cancer cells. At the same time, integrative approaches used to analyze the exhaled breath have demonstrated high sensitivity and specificity of this method for lung cancer diagnosis. Such integrative approaches include detection of smell prints by electronic nose or integrated analysis of wide range of volatile organic compounds detected by gas chromatography/mass spectrometry or related methods. Modern statistical pattern recognition systems like logistic regression analysis, support vector machine or analysis by artificial neuronal network may improve diagnostic accuracy.

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.

Detection of lung cancer in exhaled breath with an electronic nose using support vector machine analysis

Lung cancer is one of the most common malignancies and has a low 5-year survival rate. There are no cheap, simple and widely available screening methods for the early diagnostics of lung cancer. The aim of this study was to determine whether analysis of exhaled breath with an artificial olfactory sensor using support vector analysis can differentiate patients with lung cancer from healthy individuals and patients with other lung diseases, regardless of the stage of lung cancer and the most common comorbidities. Patients with histologically or cytologically verified lung cancer, healthy volunteers and patients with other lung diseases (e.g. chronic obstructive pulmonary disease (COPD), asthma, pneumonia, pulmonary embolism, benign lung tumors) were enrolled in the study. Breath sample collection and analysis with a Cyranose 320 sensor device was performed and data were further analyzed using a support vector machine (SVM). The SVM correctly differentiated between cancer patients and healthy volunteers in 98.8% of cases. The cancer versus non-cancer group patients (healthy volunteers and patients with other lung diseases) were classified correctly by SVM in 87.3% of cases. In the mixed diagnosis groups (only cancer, only COPD, cancer + COPD and control) all 79 out of 79 patients were predicted correctly in the cancer + COPD group, with the rate of correct prognosis in other patient groups being lower. Exhaled breath analysis by electronic nose using a SVM is able to discriminate patients with lung cancer from healthy subjects and mixed groups of patients with different lung diseases. It can also provide a certain level of discrimination between lung cancer patients, lung cancer patients with concomitant COPD, COPD alone and a healthy control group.

Increased innate and adaptive immune responses in induced sputum of young smokers

BACKGROUND AND OBJECTIVES It is known that chronic obstructive pulmonary disease (COPD) development process is imperceptible and can be asymptomatic for 20 or more years. It is of great importance to diagnose early inflammatory changes that can lead to COPD in young asymptomatic cigarette smokers. The aim of our study was to analyze the cell spectrum of induced sputum (IS) of young cigarette smokers, with emphasis on T-regulatory cells. MATERIALS AND METHODS A total of 20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled in the study. After lung function measurements were taken, we performed sputum induction and analyzed sputum cells. We evaluated the cell count of FOXP3-positive, CD4+ and CD8+ T lymphocytes by immunocytochemistry staining, and the cell count of macrophages and neutrophils by May-Grünwald Giemsa staining. RESULTS Induced sputum of smokers contained a higher absolute amount of macrophages and neutrophils when compared to nonsmokers. FOXP3-positive cells in the sputum of young smokers showed a statistically significant increase when compared to nonsmokers. Induced sputum of COPD patients contained an increased absolute amount of neutrophils and FOXP3-positive Treg cells when compared to nonsmokers. Regression analysis showed that the amount of FOXP-3 positive cells, neutrophils and macrophages in the induced sputum was increasing with the number of pack years. CONCLUSIONS This study demonstrates that young smokers have early inflammatory changes in their airways that not only initiate nonspecific mechanisms recruiting neutrophils, but also involve specific immune mechanisms with recruitment of T regulatory lymphocytes. The lymphocyte response is probably adaptive.

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study The aim of our study was to compare the influence of pre-treatment with H1-antihistamines (levocetirizine, desloratadine, clemastine, quifenadine, and sequifenadine) and a placebo on the histamine-induced weal and flare reaction, increase of skin blood perfusion and sedation. Thirty healthy volunteers were enrolled in the study. The study design was a prospective, randomised, double-blind, placebo-controlled, crossover, balanced clinical trial. Volunteers in randomised and double-blind order were treated with oral levocetirizine 5 mg, desloratadine 5 mg, clemastine 1 mg, quifenadine 50 mg, sequifenadine 50 mg or a placebo. Two hours after intake of medication, the histamine skin prick test was performed and skin blood perfusion was registered with further evaluation of sedative effect. We conclude that levocetirizine induced a significant and pronounced decrease of weal and flare reaction and skin blood perfusion compared to the placebo and the other H1-antihistamines. The effect of quifenadine and sequifenadine on weal reaction area was similar to desloratadine and clemastine. Regarding the sedative effect, we can conclude that second generation antihistamines appear to be not non-sedative but the least impairing, and the first generation antihistamines appear to be the most impairing on central nervous system function. There is a necessity to consider the sedating potential of antihistamines, along with other factors such as efficacy, when prescribing antihistamines to patients. H1-antihistamīni samazina papulas un eritēmas reakciju un asins perfūzijas pieaugumu ādā, izvērtējot ar lāzera Doplera plūsmas analīzes metodi: randomizēts, dubultakls, placebo kontrolēts krustota dizaina pētījums Mūsu pētījuma mērķis bija salīdzināt ietekmi, kāda piemīt pirms testa lietotiem H1-antihistamīniem — levocetirizīnam, desloratadīnam, klemastīnam, kvifenadīnam, sekvifenadīnam — un placebo uz histamīna izraisītu papulas un eritēmas reakciju, asins perfūzijas pieaugumu ādā un sedāciju. Pētījumā tika iesaistīti 30 veseli brīvprātīgie. Šis bija prospektīvs, randomizēts, dubultakls, placebo kontrolēts, krustota dizaina un balansēts klīnisks pētījums. Brīvprātīgajiem randomizētā un dubultaklā veidā tika doti perorāli 5 mg levocetirizīna, 5 mg desloratadīna, 1 mg klemastīna, 50 mg kvifenadīna, 50 mg sekvifenadīna vai placebo. Divas stundas pēc kapsulas lietošanas tika veikts ādas dūriena tests ar histamīnu, tika registrētas asins perfūzijas izmaiņas ādā, kā arī sedatīvā efekta izvērtēšana. Mēs secinājām, ka levocetirizīns izraisa visnozīmīgāko un visizteiktāko ādas papulas un eritēmas reakcijas samazinājumu, kā arī visievērojamāko asins perfūzijas samazinājumu ādā, salīdzinot ar placebo un citiem H1-antihistamīniem. Kvifenadīna un sekvifenadīna ietekme uz papulas reakciju bija līdzīga desloratadīna un klemastīna ietekmei. Attiecībā uz sedatīvo efektu var secināt, ka otrās paaudzes antihistamīni ir nevis bez sedatīvas ietekmes, bet to sedatīvā ietekme atstāj vismazāko iespaidu un sekas uz organisma funkcijām, savukārt pirmās paaudzes antihistamīni visvairāk pasliktina centrālās nervu sistēmas funkciju. Jāievēro, ka, izrakstot pacientam kādu H1-antihistamīna preparātu, jāatceras arī par to sedatīvo ietekmi, ne tikai tiešo efektu uz alergiskās reakcijas patogenētiskajiem faktoriem.