Clinical Use of Neurophysiological Biomarkers and Self-Assessment Scales to Predict and Monitor Treatment Response for Psychotic and Affective Disorders.

Psychoses and affective disorders are severe mental illnesses with a considerable negative effect on an individual and global scale. They are among the most damaging and socially significant diseases, which contribute to permanent disabilities for the patients. The aim of this review is to analyse the capacity of neuroscientific methods as tools to reform psychiatry into a biologically valid medical discipline. Furthermore, it will focus on the application of the translational approach towards the diagnostic and therapeutic processes, as well as monitoring of treatment response by using valid biomarkers and psychometric instruments. By combining translational neuroscience with the latest psychopharmacology advances, clinicians might be able to provide better quality of precision and individualized medical care for their patients. We visualise a reality in which neuroimaging methods will modify the standard clinical evaluation of neuropsychiatric disorders, leading to a biologically valid diagnosis, monitoring and treatment in everyday clinical practice.

Desaturation during Physical Exercise in COPD Patients - a Stable-over-time Phenomenon.

INTRODUCTION: Exercise-induced desaturation is a common finding in patients with moderate and severe COPD. It is an important marker in the course of disease that has a prognostic value for mortality risk. AIM: To monitor over time COPD patients with and without desaturation during 6-minute walking test (6MWT) and to assess the stability of that phenomenon. MATERIALS AND METHODS: A 6MWT was administered to 70 patients with COPD which ranged in severity from stage 2A to stage 4D (GOLD 2011); the patients had a mean age of 64.5±10.1, mean pack-years - 38.8±21, FEV1% = 46.4%±15.7%, FVC% = 73.7%±1.3%, MRC = 2.31±0.84, CAT = 20.8±6.6. Oxygen saturation was monitored during the test; indications for desaturation were a decrease of SpO2 by ≥4% and a fall in SpO2 to ≤88% for at least 3 min. The patients were followed-up for mean 40.9±22.3 months and tests were repeated. RESULTS: Patients were divided into two groups based on the decrease in SpO2: Group A included patients with desaturation (n=35) and Group B - patients with no desaturation (n=35). In 66 of the patients the desaturation profile was stable over time. Only two patients, who did not desaturated at baseline, experienced desaturation in the follow-up 6MWT and another two patients, who desaturated at baseline, did not have it later in the follow-up. CONCLUSION: Desaturation is a phenomenon that is persistent over time. Based on the results, it could be concluded that exercise-induced desaturation is a major marker of a particular COPD phenotype.

Effects of acute hypoxic provocation on the autonomic nervous system in 'healthy' young smokers, measured by heart rate variability.

AIM: The aim of this study was to compare the activity of the autonomic nervous system (ANS) using heart rate variability (HRV) in 'healthy' young smokers and non-smokers before, during and after exogenous hypoxic provocation. METHODS: Twenty-one healthy non-smoking males aged 28.0 ± 7.4 years (mean ± SD) and 14 'healthy' smoking males aged 28.1 ± 4.3 years with 9.2 ± 5.6 pack-years were subjected to one-hour hypoxic exposure (FiO2 = 12.3 ± 1.5%) via a hypoxicator. HRV data was derived via Kubios HRV, Finland software by analysing the pre-hypoxic, hypoxic and post-hypoxic periods. RESULTS: Standard deviation of the intervals between normal beats (SDNN) was higher in the non-smokers in the pre-hypoxic period (62.0 ± 32.1 vs 40.3 ± 16.2 ms, p = 0.013) but not in the hypoxic period (75.7 ± 34.8 vs 57.9 ± 18.3 ms, p = 0.167). When comparing intra-group HRV changes, shifting from hypoxic to normoxic conditions, there was an increase in the mean square root of successive R-R interval differences (RMSSD) (65.9 ± 40.2 vs 75.1 ± 45.9 ms, p = 0.011), but these changes were observed in only the group of non-smokers. CONCLUSIONS: Smoking probably impairs autonomic regulation in healthy young males and may lead to decreased HRV, even before subjective clinical signs and symptoms appear.

Response to Pharmacological Treatment in Major Depression Predicted by Electroencephalographic Alpha Power - a Pilot Naturalistic Study.

BACKGROUND: Pharmacological treatment of depression is currently led by the trial and error principle mainly because of lack of reliable biomarkers. Earlier findings suggest that baseline alpha power and asymmetry could differentiate between responders and non-responders to specific antidepressants. AIM: The current study investigated quantitative electroencephalographic (QEEG) measures before and early in treatment as potential response predictors to various antidepressants in a naturalistic sample of depressed patients. We were aiming at developing markers for early prediction of treatment response based on different QEEG measures. MATERIALS AND METHODS: EEG data from 25 depressed subjects were acquired at baseline and after one week of treatment. Mean and total alpha powers were calculated at eight electrode sites F3, F4, C3, C4, P3, P4, O1, O2. Response to treatment was defined as 50% decrease in MADRS score at week 4. RESULTS: Mean P3 alpha predicted response with sensitivity and specificity of 80%, positive and negative predictive values of 92.31% and 71.43%, respectively. The combined model of response prediction using mean baseline P3 alpha and mean week 1 C4 alpha values correctly identified 80% of the cases with sensitivity of 84.62%, and specificity of 71.43%. CONCLUSIONS: Simple QEEG measures (alpha power) acquired before initiation of antidepressant treatment could be useful in outcome prediction with an overall accuracy of about 80%. These findings add to the growing body of evidence that alpha power might be developed as a reliable biomarker for the prediction of antidepressant response.

The effect of continuous positive airway pressure on heart rate variability during the night in patients with chronic heart failure and central sleep apnoea.

Continuous positive airway pressure (CPAP) improves autonomic activity in patients with chronic heart failure (CHF) and central sleep apnoea (CSA), but its effect on heart rate variability (HRV) during therapy has not been reported. We hypothesized that CPAP may decrease HRV, despite its beneficial effects on sympathetic overactivation, due to the expected stabilization of breathing. Sixty-seven CHF patients underwent polysomnography (PSG). Ten of them presented with CSA (age 66.1±8.5 years, apnoea-hypopnea index [AHI]=57.6±23.3, central AHI [cAHI]=41.6±24.6 [mean±SD]) and were subjected to a second PSG with manual CPAP titration. Beat-to-beat heart intervals for a 6-hour period of sleep were extracted from each recording and HRV was analysed. CPAP significantly reduced AHI (AHI=23.1±18.3 P=.004). Standard deviation of normal-normal interbeat interval (SDNN) (61.5±29.0 vs 49.5±19.3 ms, P=.021), root mean square of successive differences (RMSSD) (21.8±9.2 vs 16.4±7.1 ms, P=.042), total power (lnTP=7.8±1.1 vs 7.4±0.8 ms2 , P=.037), low frequency power (lnLF=5.5±1.5 vs 5.0±1.4 ms2 , P=.003) and high frequency power (lnHF=4.6±1.0 vs 4.0±1.0 ms2 , P=.024) were decreased. There was a strong correlation between the decrease in AHI and the decrease in lnHF (Spearman's ρ=.782). CPAP leads to a decrease in spectral and time domain parameters of HRV during therapy in CHF patients with CSA. These changes are best explained by the effect which CPAP-influenced breathing pattern and lowered AHI exert on HRV.

Identifying Predictors of Central Sleep Apnea/Cheyne-Stokes Breathing in Chronic Heart Failure: a Pathophysiological Approach.

Chronic heart failure (CHF) is a major health problem associated with increased mortality, despite modern treatment options. Central sleep apnea (CSA)/Cheyne-Stokes breathing (CSB) is a common and yet largely under-diagnosed co-morbidity, adding significantly to the poor prognosis in CHF because of a number of acute and chronic effects, including intermittent hypoxia, sympathetic overactivation, disturbed sleep architecture and impaired physical tolerance. It is characterized by repetitive periods of crescendo-decrescendo ventilatory pattern, alternating with central apneas and hypopneas. The pathogenesis of CSA/CSB is based on the concept of loop gain, comprising three major components: controller gain, plant gain and feedback gain. Laboratory polysomnography, being the golden standard for diagnosing sleep-disordered breathing (SDB) at present, is a costly and highly specialized procedure unable to meet the vast diagnostic demand. Unlike obstructive sleep apnea, CSA/CSB has a low clinical profile. Therefore, a reliable predictive system is needed for identifying CHF patients who are most likely to suffer from CSA/CSB, optimizing polysomnography use. The candidate predictors should be standardized, easily accessible and low-priced in order to be applied in daily medical routine. The present review focuses on a pathophysiological approach to the selection of some predictors based on parameters reflecting the etiology, the pathogenesis and the consequences of CSA/CSB in CHF.

Heart Rate Variability as a Method for Assessment of the Autonomic Nervous System and the Adaptations to Different Physiological and Pathological Conditions.

The autonomic nervous system controls the smooth muscles of the internal organs, the cardiovascular system and the secretory function of the glands and plays a major role in the processes of adaptation. Heart rate variability is a non-invasive and easily applicable method for the assessment of its activity. The following review describes the origin, parameters and characteristics of this method and its potential for evaluation of the changes of the autonomic nervous system activity in different physiological and pathological conditions such as exogenous hypoxia, physical exercise and sleep. The application of heart rate variability in daily clinical practice would be beneficial for the diagnostics, the outcome prognosis and the assessment of the effect of treatment in various diseases.

Evaluation of Acute Exogenous Hypoxia Impact on the Fraction of Exhaled Nitric Oxide in Healthy Males.

INTRODUCTION: Exogenous hypoxia increases ventilation and contracts the pulmonary vessels. Whether those factors change the values of nitric oxide in exhaled air has not yet been evaluated. OBJECTIVE: To examine the effect of exogenous normobaric hypoxia on the values of the fraction of nitric oxide in exhaled breath (FeNO). Subjects аnd Methods: Twenty healthy non-smoker males at mean age of 25.4 (SD = 3.7) were tested. The basal FeNO values were compared with those at 7 min. and 15 min. after introducing into the hypoxic environment (hypoxic tent), imitating atmospheric air with oxygen concentration corresponding to 3200 m above sea level. Exhaled breath temperature was measured at baseline and at 10-12 min. of the hypoxic exposition. Heart rate and oxygen saturation were registered by pulse-oximetry. RESULTS: All the subjects had FeNO values in the reference range. The mean baseline value was 14.0 ± 3.2 ppb, and in hypoxic conditions - 15.5 ± 3.8 ppb (7 min.) and 15.3 ± 3.6 ppb (15 min.), respectively, as the elevation is statistically significant (p = 0.011 and p = 0.008). The values of exhaled breath temperature were 33.79 ± 1.55°Ð¡ and 33.87 ± 1.83°Ð¡ (p = 0.70) at baseline and in hypoxic conditions, respectively. Baseline oxygen saturation in all subjects was higher than that, measured in hypoxia (96.93 ± 1.29% vs. 94.27 ± 2.53%; p < 0.001). CONCLUSIONS: Exogenous hypoxia leads to an increase of FeNO values, but does not affect the exhaled breath temperature.

Somatosensory evoked potentials in full-term neonates with perinatal asphyxia.

OBJECTIVE: To explore the capacity of somatosensory evoked potentials (SEP) to assess maturation processes in the development of the nervous system, and the characteristics of SEP in healthy full-term infants and full-term newborns with perinatal asphyxia and their follow up until the age of 14 months. MATERIALS AND METHODS: SEP were studied in 21 healthy full-term infants and 38 full-term newborns with perinatal asphyxia. The children with asphyxia were studied longitudinally until they were 14 months old. To assess the SEP we measured the latency of the P15, N20 and P25 components, the amplitude ratio N20/P25 and inter-peak intervals P15-N20 and N20-P25. RESULTS: The component that was most typically always found in the SEP recordings of both healthy infants and those with perinatal asphyxia was N20. The mean latency values of P15, N20 and P25 were higher in the children with perinatal asphyxia (p < 0.001). The SEP amplitude was highly variable (CoV% = 76.6%). The latencies became shorter with age in asphyxia patients aged 0 to 14 months, the shortening being the greatest in the first trimester, while they showed no statistically significant differences in infants aged 6 to 12 months. CONCLUSIONS: SEPs in the neonatal period differ considerably from those of adults and older children in the morphology and longer potential latency, which can be accounted for by the incomplete myelination of nerve fibers. The changes in SEP latency in patients with HIE stages I and II follow the same pattern found in healthy children--latency became shorter with increasing age, which was most pronounced in the first 3 months. SEP latency was found to be correlated with height and age. No differences were found in the latency of potentials between healthy infants and infants with brain hemorrhage. Recording SEP is a sensitive method to assess the CNS in children with perinatal asphyxia and to monitor the maturation of the somatosensory pathway.

Reference values for forced expiration parameters in Bulgarian children and adolescents aged 7 to 18 years.

INTRODUCTION: A diagnosis of lung function impairment in childhood is highly dependent on the respective reference values. Population differences in the pulmonary function of children have been frequently reported. The AIM of this study was to derive normal spirometric reference values for Bulgarian children and adolescents and to compare these results with other data set including our own reference equations developed 20 years ago. MATERIAL AND METHODS: Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and parameters of maximum expiratory flow-volume curves were measured in 671 healthy Bulgarian school children (339 males and 332 females) aged 7-18 years. Multiple linear regression analysis was performed for each spirometric parameter against age, height, weight, chest circumferences and fat free mass in both sexes. RESULTS: Excluding ratios, all measured spirometric parameters increased nonlinearly with age and height, and were significantly higher in boys than girls in adolescence. Height (H) explained the maximum variance for spirometric parameters and the best-fit regression equation relating functional parameters and body height was a power function (Y = a.Hb). FVC and FEV1 showed close correlations with height (r2 between 0.85 and 0.92), whereas the coefficients of determination for the flows were less close (r2 from 0.85 for PEF to 0.67 for MEF25%; always higher in boys). CONCLUSIONS: The developed prediction equations can be used in clinical practice. In comparison with reference equations based on European or USA populations, regional reference values are biologically more suitable for the interpretation of spirometric data.

Oxygen uptake efficiency slope in patients with chronic heart failure and coexisting respiratory disease.

BACKGROUND: Oxygen uptake efficiency slope (OUES) is proposed as an objective index of cardiorespiratory functional reserve. The AIM of the present study was to evaluate the effect of coexisting respiratory diseases on OUES in patients with chronic heart failure (CHF) (New York Heart Association class II-III) during incremental exercise testing. PATIENTS AND METHODS: Fifty-five males were allocated to three groups: group 1-19 patients with only CHF (CHF); group 2-17 patients with CHF and a history of respiratory disease (CHF-RD); group 3-19 matched controls (C). They all underwent comprehensive lung function testing and symptom-limited ramp cardiopulmonary exercise test on a cycle ergometer. RESULTS: The patients with a history of respiratory diseases had the lowest value of OUES, but their results were not significantly different from those of the CHF patients (OUES mL.min(-1).logL(-1)= 1461 +/- 268 vs. 1571 +/- 383 vs. 2112 +/- 263 in controls). Significant correlation was found between OUES and important functional variables: VO2peak (r=0.833), V(E)/NCO2 slope (r = -0.757), FEV1 (r=0.582), T(L,CO) (r=0.574), and EF% (r=0.350). CONCLUSIONS: OUES is significantly reduced in patients with CHF and tends to be lower in the presence of a respiratory disease. It can be regarded as an useful, reliable physiologic marker of reduced ventilatory efficiency and cardiorespiratory reserve in chronic heart failure.

Multidimensional system for assessment of COPD patients. Comparison with BODE index.

AIM: To present the principles of a multidimensional system for assessment of COPD patients, called DOREMI BOX, and to compare it with BODE index. The letters of the abbreviation stand for the following: D--dyspnea, O--obstruction, RE--rate of exacerbation, MI--movement (exercise) intolerance, B--Body Mass Index, OX--blood oxygen disturbances. METHODS: For validation of DOREMI BOX we tested 84 patients with COPD (age = 59 +/- 9 years, FEV1% = 35 +/- 14%; Charlson index = 2.7 +/- 1.0) in clinically stable condition. The prognostic value of the new system was validated prospectively in a cohort of 68 COPD patients followed-up for a minimum of 36 months. RESULTS: The mean value of DOREMI BOX score was 6.0 +/- 1.8 (range = 3-10), and for BODE index--4.7 +/- 2.2 (range = 1-10). Construct validity has been demonstrated between DOREMI BOX score and symptoms score (R=0.52; P<0.001). DOREMI BOX score correlates strongly with the classic indices for assessment and staging of COPD--FEV1%, dyspneic scales, blood gases, 6MWD, which proves its concurrent validity. After 36 months there were 22 deaths and 46 survivals. Patients with higher DOREMI BOX score were at a higher risk of death. The hazard ratio for death from any cause per one-point increase in the DOREMI BOX score was 1.44 (95% CI, 1.06-1.95; P=0.009). CONCLUSIONS: DOREMI BOX has construct and concurrent validity for assessment of COPD and slightly better ability than BODE index to predict risk for death in COPD patients.

Exercise performance in children with severe beta-thalassemia before and after transfusion.

UNLABELLED: Thalassemia major is associated with impaired exercise tolerance because of the severe anemia and cardiopulmonary dysfunction characteristic of the condition. OBJECTIVE: To assess the exercise performance in thalassemic children before and two hours after hemotransfusion. PATIENTS AND METHODS: The study included eleven children with thalassemia major (12.3 +/- 2.8 years; Hb g/dl = 8.1 +/- 1.3) and 11 matched controls. All subjects underwent comprehensive pulmonary function assessment and incremental exercise test on a treadmill. RESULTS: The thalassemic children were, in general, shorter and lighter than their healthy counterparts; we also found lower absolute values of lung function parameters which did not reach statistical significances. On the other hand the most considerable differences were found in diffusion capacity (uncorrected TL(L,CO) % = 56.8 +/- 12.1 vs. 94.3 +/- 16.1 in controls; p<0.001) and blood oxygen content (ctO2 mmol.L(-1) = 4.7 +/- 1.1 vs. 8.3 +/- 0.8, p<0.05). The thalassemic children had significantly lower exercise capacity compared to controls (VO2/ kg = 27.1 +/- 5.0 vs. 37.1 +/- 3.2 mL.min(-1).kg(-1); p<0.001). In the patients' group hemoglobin was elevated significantly two hours after transfusion (Hb g/L from 80.5 +/- 12.7 to 93.6 +/- 10.6; p<0.001) leading to significant improvement in exercise duration (7.3 +/- 2.8 vs. 10.3 +/- 2.3 min; p<0.05), VO2/kg (28.5 +/- 5.0 vs. 36.2 +/- 7.1 mL.min(-1).kg(-1); p<0.05), and transfer factor (4.27 +/- 1.40 vs. 5.41 +/- 1.08 mmol.min(-1).kPa(-1); p=0.003). There were strong correlations between Hb and TL(L,CO) and VO2 (r = 0.687 and 0.750, respectively; p < 0.01 for both). CONCLUSIONS: Patients with thalassemia major have a seriously reduced transfer factor and exercise impairment. The short-term changes in hemoglobin concentration are associated with significant improvement in exercise performance.

Assessment of respiratory compensation phase during graded exercise in patients with chronic heart failure.

BACKGROUND: The VE-VO2 relationship during graded exercise has an inflection point beyond the ventilatory anaerobic threshold (VAT) termed the respiratory compensation point (RCP). Metabolic variables analyzed at the level of VAT and RCP may contribute to the better understanding of such limiting symptoms in chronic heart failure (CHF) patients as dyspnea and early fatigue. The AIM of the present study was to analyze the RCP during symptom limited ramp exercise testing in CHF patients. PATIENTS AND METHODS: Forty six CHF patients (II and III NYHA functional class; age = 51 +/- 9 years, LVEF% = 35% +/- 6%; mean +/- SD) and 20 matched controls performed graded cardiopulmonary exercise test on a cycle ergometer. RESULTS: The duration and productivity of RCP (delta(x) = peak(x) - VAT(x)) in patients were significantly (p < 0.001) reduced compared to healthy subjects: delta duration = 3.0 +/- 1.2 vs 4.3 +/- 1.5 min, delta watts = 24.3 +/- 11.5 vs. 39.4 +/- 11.5, delta VO2/kg (ml.kg-1 x min-1) = 3.8 +/- 1.3 vs 8.8 +/- 2.3. An important characteristic of this phase was the higher subjective cost of physical effort assessed by Borg scale and Watts/Borg ratio (Borg peak = 9.9 +/- 0.4 vs. 6.0 +/- 1.2; p < 0.001, Watts/Borg peak = 9.2 +/- 2.3 vs 23.9 +/- 6.4, p < 0.001). The relative hyperventilation of patients on the basis of the watt exercise can be seen in the values of derivative index V (ml x min-1 x watt-1) 478 +/- 59 vs 568 +/- 118; (p < 0.001) in controls and patients, respectively. CONCLUSIONS: The impaired efficiency of oxygen delivery systems in patients with CHF is what causes the appearance of early limiting symptoms. Duration and productivity of respiratory compensation phase in CHF patients are considerably reduced compared to controls.

Respiratory and cardiovascular functions among smoking and nonsmoking girls from two regions with different air pollution degree.

AIM: The aim of the present study was to analyze the respiratory and cardiovascular functions among smoking and nonsmoking girls attending two schools situated in regions with different levels of air pollution. The characteristic of air pollution is based on the data gathered by stations 1 and 2 belonging to the Uniform National System for Monitoring the Air Pollution in Bulgaria. The participants (n=108, 16.07+/-0.80 years) were separated in two groups: smokers (S1 - from school 1, S2 - from school 2) and nonsmokers (NS1 - from school 1, NS2 - from school 2). All of them performed pulmonary function testing and .cardiopulmonary exercise testing on a treadmill using our modification of the Balke protocol (Marinov et al., 2000). Reference values for European children, previously validated for the Bulgarian population, were used. RESULTS: There are no significant differences in mean levels of VC, IC, FEV1, MEF50 and MEF25 (as a percentage from the predicted value as well). The average level of the Tiffneau index is noticeably higher among nonsmokers from the two regions and is the lowest among smokers from the more polluted area, but a significant difference exists between S2 (88.7+/-5.9) and NS2 (92.6+/-4.7), p=0.047; T(L,CO)%pred: S1 (85.4+/-7.2) vs. S2 (86.7+/-8.2), p=0.048 and NS1 (88.3+/-8.2) vs. NS2 (92.8+/-14.5), p=0.037; V(E)%pred: S1 (127.5+/-9.6) vs. S2 (123.7+/-6.1), p=0.035; higher levels of total lung capacity (TLC%pred), S1 (107.3+/-9.2) vs. NS2 (104.3+/-9.1), p=0.009 and alveolar ventilation (VA), S1 (5.0+/-0.6) vs. NS2 (4.6+/-0.5), p=0.008. CONCLUSIONS: 1. The negative effects of the combined influence of tobacco smoking and air pollution on some respiratory and cardiovascular functions of adolescent girls are more pronounced than each influence alone. 2. The cardiopulmonary exercise test gives adequate information about the combined effect of air pollution and smoking and using it for preventive purposes is an advisable method.

Maximal inspiratory pressure predicts mortality in patients with chronic obstructive pulmonary disease in a five-year follow-up.

INTRODUCTION: The therapeutic modality for the treatment of COPD depends on the proper determination of all factors that may have an effect on the course and prognosis of the disease. AIM: To assess the prognostic role of maximal inspiratory pressure (PImax) and a large group of lung function parameters in patients with COPD followed up over a period of five years. PATIENTS AND METHODS: A cohort of 63 COPD patients (age 58.6 +/- 8.8 yrs, BMI 24.2 +/- 5.6, FEV1% = 35 +/- 14%, PImax = 52.3 +/- 19.0 cm H2O; x +/- S x) was recruited for a 5-year prospective study. Mortality was assessed as overall mortality. The independent predictors of survival were determined using the Cox proportional hazards model. RESULTS: The deceased patients (n = 32) had lower values of BMI, FEV1, DL(CO)/V(A)%, PaO2, PImax, and six-minute walking test (6MWT) and higher RV/TLC% (p < 0.05) than the survivors. The regression model included the following parameters: age, BMI, smoking history, FEV1, FVC, DL(CO)/V(A)%, lung hyperinflation (RV/TLC%), PImax, PaO2, PaCO2, hematocrit, mean pulmonary artery pressure (mPAP - Doppler echocardiography), symptoms (Anthonisen scale), dyspnea, comorbidity (Charlson index), frequency of exacerbations in the previous year, and the exercise capacity (6MWT). Statistical analysis indicated that PImax was an independent predictor of mortality (p = 0.005). CONCLUSION: Low PImax was associated with greater overall mortality rate in this cohort of patients with COPD.

Long-term changes in dyspnea, lung function, and exercise capacity in COPD patients.

OBJECTIVE: To examine longitudinal changes in dyspnea, lung function, and exercise capacity in COPD patients and to compare baseline data of frequent and infrequent exacerbators at trial entry. METHODS: Nineteen stable COPD patients without significant co-morbidity (age, 58.4 +/- 8.4 years; FEV1% = 33 +/- 12%; mean +/- SD) participated in the study. After a mean period of 36 months (range = 24 - 49) the patients were retested using an identical protocol. RESULTS: Repeated measures analysis showed that there was significant deterioration of FEV1 L (from 1.028 +/- 0.349 to 0.928 +/- 0.307; p = 0.007), PImax cm H2O (from 61.9 +/- 24.2 to 42.0 +/- 22.1; p = 0.007), PaO2 mm Hg (from 69.0 +/- 8.6 to 60.1 +/- 6.8; p = 0.003), PaCO2 mm Hg (from 43.1 +/- 4.9 to 47.3 +/- 4.5; p = 0.001), ATS (from 2.4 +/- 1.0 to 2.8 +/- 0.8; p = 0.031), and 6MWD m (from 389 +/- 130 to 341 +/- 135; p = 0.014). There were also changes in IC, T(L,CO)/V(A), PAP and Borg, but they were not statistically significant. Differentiation of patients by frequency of exacerbations per year of observation (> 2 < or =) discriminated them with respect to functional parameters (FEV1, FVC, IC), dyspneic indices (ATS, VAS and Borg) and exercise capacity (6MWD) at the time of enrollment. CONCLUSIONS: 1) Lung function parameters, blood-gas and dyspneic indices, and exercise capacity decline over a mean period of 36 month in patients with COPD; 2) Patients with frequent exacerbations experience more dyspnea and have lower levels of lung function and exercise capacity at trial entry.

Tidal breathing analysis in school-age children. Comparison with the parameters of forced expiration.

UNLABELLED: Tidal breathing analysis is a method which has the potential to be used for distinguishing and follow-up of airflow obstruction (AFO) in infants, children and critically ill patients. The aim of the present study was to analyse the tidal breathing parameters (TBP) in healthy and in asthmatic school-age children and to compare them with the parameters of forced expiration. SUBJECTS: Two hundred and twenty five healthy children and 100 asthmatics (7 to 14 years- old) took part in the present study. RESULTS: The results show that TBPs exhibit great inter- and intraindividual variability, even if the mean value of 10 consecutive breathing cycles is used. Parameters that reflect the tidal expiratory flow pattern--V(PTEF)/V(E) and T(PTEF)/T(E) demonstrate high variability and no correlation with age, sex and anthropometric parameters in healthy children. These indices are useful for detection of acute changes in bronchomotor tonus in asthmatics - V(PTEF)/V(E) = 36.1 +/- 6.6% vs. 32.6 +/- 6.2% (methacholine) vs. 37.4 +/- 7.5% (salbutamol) and T(PTEF)/T(E) = 34.2 +/- 6.2% vs. 28.6 +/- 7.8% vs. 35.3 +/- 7.5%, resp. (P < 0.05 everywhere; n = 34) as well as for discriminating a group of subjects with AFO vs. controls (V(PTEF)/V(E) = 30.9 +/- 6.5% vs. 35.3 +/- 8.0%; P = 0.005, and T(PTEF)/T(E) = 29.0 +/- 6.7% vs. 32.8 +/- 7.6%; P = 0.016). The evaluation of the area under the ROC curves (AUC) in the asthmatic group showed weak discriminative capacity of T(PTEF)/T(E) and V(PTEF)/V(E) in comparison to FEV1 (AUC of T(PTEF)/T(E) = 0.62; 95%CI 0.51-0.74). CONCLUSIONS: Tidal breathing parameters could add insight t.o the functional profile but are not capable of substituting forced expiration regarding detection of overt airflow obstruction in school-age children.