Romanian Guidelines for the Diagnosis and Treatment of GERD-induced Respiratory Manifestations.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common condition present in daily practice with a wide range of clinical phenotypes. In this line, respiratory conditions may be associated with GERD. The Romanian Societies of Gastroenterology and Neurogastroenterology, in association with the Romanian Society of Pneumology, aimed to create a guideline regarding the epidemiology, diagnosis and treatment of respiratory conditions associated with GERD. METHODS: Delphi methodology was used and eleven common working groups of experts were created. The experts reviewed the literature according to GRADE criteria and formulated 34 statements and recommendations. Consensus (>80% agreement) was reached for some of the statements after all participants voted. RESULTS: All the statements and the literature review are presented in the paper, together with their correspondent grade of evidence and the voting results. Based on >80% voting agreement, a number of 22 recommendations were postulated regarding the diagnosis and treatment of GERD-induced respiratory symptoms. The experts considered that GERD may cause bronchial asthma and chronic cough in an important number of patients through micro-aspiration and vagal-mediated tracheobronchial reflex. GERD should be suspected in patients with asthma with suboptimal controlled or after exclusion of other causes, also in nocturnal refractory cough which needs gastroenterological investigations to confirm the diagnosis. Therapeutic test with double dose proton pump inhibitors (PPI) for 3 months is also useful. GERD induced respiratory conditions are difficult to treat; however,proton pump inhibitors and laparoscopic Nissen fundoplication are endorsed for therapy. CONCLUSIONS: This guideline could be useful for the multidisciplinary management of GERD with respiratory symptoms in current practice.

Increased Vascular Endothelial Growth Factor Serum Level and the Role of +936C/T Gene Polymorphism in Chronic Obstructive Pulmonary Disease.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) represents a debilitating disease, with rising morbidity and mortality. Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, vascular permeability, and airway remodeling. The purpose of this study was to investigate the relationship between VEGF serum levels and VEGF +936 C/T gene polymorphism (rs3025039) with COPD, for the first time in a Romanian population. Materials and Methods: In total, 120 participants from Transylvania were included in this case-control study. Serum levels of VEGF were determined using an enzyme-linked immune-sorbent assay and rs3025039 was investigated by high molecular weight genomic deoxyribonucleic acid (DNA). Spirometric values, arterial blood gas analysis, and the Six Minute Walk Test (6MWT) outcome were also determined. Results: The serum level of VEGF was higher in the COPD group versus controls (p < 0.001), with a positive correlation with the 6MWT outcome. No significant difference was observed in the VEGF serum levels between VEGF +936C/T genotypes. There was no difference in the VEGF +936C/T genotype between COPD patients and healthy subjects (chi2 test p = 0.92, OR = 1.04, 95%CI = 0.41-2.62), but the presence of the T allele was significantly linked to the presence of COPD (chi2 test p = 0.02, OR = 2.36, 95%CI = 1.12-4.97). Conclusions: Higher VEGF serum levels were found in moderate and severe COPD and were positively correlated with the distance in the 6MWT. No significant difference was found between CC, CT, and TT genotypes of rs3025039 and the presence of COPD. The presence of the T allele was found to be linked to COPD and also to the degree of airway obstruction.

Alveolar proteinosis - an underdiagnosed condition in young people.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by an abnormal intra-alveolar accumulation of surfactant derived lipoproteinaceous compounds, leading to dyspnea and, in severe cases, to respiratory failure. The most common form of PAP is the auto-immune one. Secondary PAP has been recognized in myeloid leukemia, non-hematological neoplasms, lung infections or environmental exposure to noxious particles. Mutations in several genes (such as MARS, SFTPB, TTF1) are responsible for the alteration of surfactant production. Diagnosis tools include high-resolution computed tomography, bronchoalveolar lavage. Although over the past 20 years the pathophysiology of PAP has become more clear, the therapeutic strategies still need improvement. A national programme for patients with PAP might be useful in Romania.

Modification of exhaled air nitric oxide in patients with asthma - cortisone monotherapy or dual inhalation therapy?

INTRODUCTION: Asthma, a chronic lung disease, is a major health challenge worldwide with increased addressability to health services. There are different asthma phenotypes, which have different evolution and can be specifically tracked. The measurement of fractional expired nitric oxide (FeNo) with different devices reflects the eosinophilic inflammation of the airways, and can be used to evaluate the allergic phenotype and predict the treatment responses. The new GINA (Global Initiative for Asthma) guideline recommends FeNO monitoring to assess adherence to cortisone treatment in high doses before prescribing biological treatment, and as a means of monitoring the decrease in oral corticosteroid treatment. OBJECTIVE: The aim of the study is to analyze the applicability of FeNO in monitoring response to therapy. MATERIAL AND METHODS: An observational study was carried out on 129 subjects with a previously established diagnosis of asthma. The research was based on the determination of FeNO with NObreath. Those with intermediate FeNO received a low dose of inhaled corticosteroids in mono/dual therapy, those with increased FeNO received medium ICS mono/dual therapy. FeNO testing, its values and doses of ICS were below the the ATS / ERS guidelines. RESULTS: FeNO reduction is strictly dependent on the cortisone dose. Applying the dual therapy from the beginning does not bring additional benefits in comparison with cortisone in monotherapy, in terms of FeNO value. CONCLUSIONS: Recommendations that include FeNO testing can help monitor response to treatment.

Diagnostic Value of the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) in Various Respiratory Diseases: A Retrospective Analysis.

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) ratio are two extensively used inflammatory markers that have been proved very useful in evaluating inflammation in several diseases. The present article aimed to investigate if they have any value in distinguishing among various respiratory disorders. One hundred and forty-five patients with coronavirus disease 2019 (COVID-19), 219 patients with different chronic respiratory diseases (interstitial lung disease, obstructive sleep apnea(OSA)-chronic obstructive pulmonary disease (COPD) overlap syndrome, bronchiectasis) and 161 healthy individuals as a control group were included in the study. While neither NLR nor PLR had any power in differentiating between various diseases, PLR was found to be significant but poor as a diagnostic test when the control group was compared with the OSA-COPD group. NLR was found to be significant but poor as a diagnostic test when we compared the control group with all three groups (separately): the OSA-COPD group; interstitial lung disease group, and bronchiectasis group. NLR and PLR had poor power to discriminate between various respiratory diseases and cannot be used in making the differential diagnosis.

Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve.

Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated. The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence. Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca. We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups. Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations. Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS). Overall, pneumologist adherence was 79.02%. The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A. Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy. Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021). ICS overprescription was the most common type of inappropriateness (17.81%). Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004). Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved. Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important. ICS represent the most prescribed overtreatment. Further multicentric studies are needed to evaluate all factors that might influence the adherence rate.

Disease Perception and Coping with Emotional Distress During COVID-19 Pandemic: A Survey Among Medical Staff.

The novel coronavirus disease, COVID-19, is a highly contagious infectious disease declared by the World Health Organization to be a pandemic and a global public health emergency. During outbreaks, health care workers are submitted to an enormous emotional burden as they must balance the fundamental "duty to treat" with their parallel duties to family and loved ones. The aims of our study were to evaluate disease perceptions, levels of stress, emotional distress, and coping strategies among medical staff (COVID-19 versus non-COVID-19 departments) in a tertiary pulmonology teaching hospital in the first month after the outbreak of COVID-19. One hundred and fifteen health care workers completed four validated questionnaires (the brief illness perception questionnaire, perceived stress scale, the profile of emotional distress emotional, and the cognitive coping evaluation questionnaire) that were afterwards interpreted by one psychologist. There was a high level of stress and psychological distress among health care workers in the first month after the pandemic outbreak. Interestingly, there were no differences between persons that worked in COVID-19 departments versus those working in non-COVID-19 departments. Disease perceptions and coping mechanisms were similar in the two groups. As coping mechanisms, refocusing on planning and positive reappraisal were used more than in the general population. There is no difference in disease perceptions, levels of stress, emotional distress, and coping strategies in medical staff handling COVID-19 patients versus those staff who were not handling COVID-19 patients in the first month after the pandemic outbreak.

Correlations between neutrophil to lymphocyte ratio, blood eosinophils and clinical characteristics in chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide, with increasing mortality and morbidity. The neutrophil to lymphocyte ratio (NLR) and blood eosinophils level (EOS) represent biomarkers of inflammation in various diseases, with current research in the field of COPD. The aim of this study was to determine correlations of NLR and EOS with certain characteristics of COPD in a group of patients without major comorbidities. METHODS: We conducted an observational study on COPD patients admitted to the Clinical Hospital of Pneumology in Cluj-Napoca, Romania. The smoking history, body mass index (BMI), NLR, EOS, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the arterial partial pressure of oxygen (PaO2) were determined. Functional assessment consisted of spirometric and BODE index determinations. The duration of hospitalization was expressed as the length of stay (LOS). The patients were divided into 3 subgroups: active smokers (AS), former smokers (FS) and never smokers (NS). RESULTS: No significant differences between AS and FS were found when age, airway obstruction, BODE index, PaO2, ESR and CRP were considered. The NLR was higher in AS versus FS (p=0.035), while EOS was lower in AS group (p=0.061). COPD patients with ≥300 EOS/µL had lower CRP, ESR levels and NLR compared to those with eosinophilia <300/µL (p=0.020, p=0.009 and p=0.007, respectively). With a threshold of 3.5 for NLR, patients with lower NLR had lower CRP values (p=0.05). COPD patients with higher NLR had significant lower EOS levels (p=0.018). Overall, the NLR and EOS were not correlated with the investigated characteristics (p>0.05), but intragroup analysis (based on smoking status) revealed correlations with ESR (p=0.0001), CRP (p=0.053), BODE index (p=0.029) and LOS (p=0.042). CONCLUSIONS: AS have higher NLR and lower EOS levels versus FS. COPD patients with higher EOS level have lower CRP, ESR and NLR. In AS, EOS level is positively correlated with BODE index and negatively correlated with NLR.

The impact of continuous positive airway pressure on cardiac arrhythmias in patients with sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) can lead to cardiac complications: brady and tachyarrhythmias and sudden cardiac death. Continuous positive airway pressure (CPAP) is the gold standard for the treatment of OSA. The present study aims to demonstrate the efficiency of CPAP in the treatment of cardiac arrhythmias in patients with OSA. The study also recorded the frequency of arrhythmias in patients with untreated OSA and assessed the association between the severity of OSA and the occurrence of arrhythmias. MATERIALS AND METHODS: This is a prospective cohort study. Ninety-three patients with OSA were included, aged 60 (58-64) years, with female/male sex ratio of 1:4. They were subjected simultaneously to home respiratory polygraphy examination and Holter electrocardiogram monitoring, in two different stages: at diagnosis and at the 3-month checkup after CPAP treatment. The presence of supraventricular and ventricular arrythmias was noted. Respiratory parameter values were also recorded. RESULTS: Statistically significant decrease in the occurrence of supraventricular (P < 0.001) and ventricular extrasystoles (P < 0.001), atrial fibrillation (AF) (P = 0.03), nonsustained ventricular tachycardia (NSVT) (P = 0.03), and sinus pauses (P < 0.001) was observed 3 months after treatment with CPAP, compared with baseline. The apnea-hypopnea index (AHI) was correlated with the ventricular extrasystoles (r = 0.273; P = 0.008). The ejection fraction of the left ventricle was inversely correlated with the episodes of NSVT (r = -0.425; P < 0.001). AF was associated with the longest apnea (r = 0.215; P = 0.04). Cardiac activity pauses were correlated with AHI (r = 0.320; P = 0.002), longest apnea (r = 0.345; P = 0.01), and oxygen desaturation index (r = 0.325; P = 0.04). CONCLUSION: The prevalence of cardiac arrhythmias in patients with OSA was reduced after 3 months of CPAP therapy. Cardiac arrhythmias were correlated with the severity of OSA.

CD4+ regulatory T cells and CD4+ activated T cells in new active and relapse tuberculosis.

The aim of the present study was to examine characteristics of tuberculosis (TB) patients with different clinical forms and to study the frequency of Regulatory T cells (Treg cells) and Activated T cells in patients with new active and relapse TB. Forty-five pulmonary TB patients and a control group of 15 healthy individuals were enrolled in this study. Of the 45 TB patients, 15 were new cases with drug-susceptible active TB and 30 were relapsed cases (15 drug-susceptible and 15 multidrug resistant-TB). The age of study participants ranged from 21 to 68 years old. According to sex presentation, males were appreciably highly affected than females with a sex ratio of 2. The patients reported a mean recent weight loss of 8.9 kg. The Erythrocyte Sedimentation Rate was high in TB group, far exceeding the normal value. The results revealed that the number of CD3+ CD4+ T-cells significantly decreased whereas the level of blood Treg cells and expression of activation markers CD38 and HLA-DR on CD4+ T-cells significantly increased in TB group compared with the control group (p<0.05). The frequency of Treg cells was significantly higher in the TB group than the control group. Both the patients with new active TB and relapse TB demonstrated significantly higher levels of CD4+FoxP3+ Treg compared to healthy subjects (p<0.05). A high and significant percentage of Treg cells were found in patients with DS active TB than patients with MDR relapse TB. Interestingly, the frequency of CD4+FoxP3+ cells also differs according to the sputum smear microscopy status. The presence of high numbers of Treg cells and corresponding high immune activation may be an unfavourable factor that can predispose individuals to different clinical forms of TB, including relapse TB.

Fatal hypersensitivity pneumonitis after chemical occupational exposure.

Hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis) is a rare non-immunoglobulin E (IgE)-mediated inflammatory lung disease caused by inhalation exposure (occupational, recreational or ordinary home exposure). A 36-year-old female patient, without significant medical history, is referred to an outpatient pulmonology clinic for dry cough, shortness of breath, fever, fatigue and weight loss. Chest high-resolution computed tomography (HRCT) was performed, and significant lung fibrosis (especially centrilobular and interlobular in bilateral "thick lines"), traction bronchiectasis and alveolitis in both superior lobes are described. Lung function tests showed severe restrictive dysfunction. Transfer factor of the lung for carbon monoxide (TLCO) being very low, the flexible bronchoscopy was contraindicated. Surgical lung biopsy was performed. Histopathological examination showed characteristic lesions of chronic bilateral hypersensitivity pneumonitis. The patient died four days after the surgical intervention due to post-operative complications. Exposure to various chemical substances can form bonds with human proteins molecules and induce an exaggerated immune response in susceptible individuals. A high index of suspicion of occupational exposure can determine an early diagnosis with a better outcome.

The value of laboratory tests in the diagnosis of tuberculosis.

BACKGROUND AND AIM: In the last decades, the inhabitants of the Romanian region known as Jiu Valley underwent changes in their social and economic status which determined changes in behaviour and health, which influenced their general health condition. One of the consequences was the exacerbation of tuberculosis. In order to control this situation, there was a need to increase the efficiency of diagnosis. This optimization can be reached by a better detection of mycobacterium infection, optimal isolation of strains and identification of the resistance of strains to antituberculous drugs. METHODS: In order to identify the best diagnostic modality, we compared the efficacy of the classical bacteriological diagnosis, still performed in the field, to the modern methods of molecular biology. The study included two groups, one represented by 213 patients who were investigated using the classical bacteriological methods, and 49 who were diagnosed using the PCR method. RESULTS: The tuberculosis patients who have been evaluated only with the classical bacteriological methods where diagnosed as TB positive and treated according to the national guidelines, which are in agreement with the international guidelines. The PCR diagnostic methods had a superior diagnostic value compared to the traditional bacteriological method. CONCLUSIONS: The results revealed the superiority of the modern molecular biology methods based on PCR. However the bacteriological method remains useful in areas where PCR cannot be afforded.

Texture analysis using proton density and T2 relaxation in patients with histological usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP).

OBJECTIVES: The purpose of our study was to assess proton density (PD) and T2 relaxation time of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) and to evaluate their utility in differentiating the two patterns. Furthermore, we aim to investigate whether these two parameters could help differentiate active-inflammatory and stable-fibrotic lesions in NSIP. METHODS: 32 patients (mean age: 69 years; M:F, 1:1) with pathologically proven disease (UIP:NSIP, 1:1), underwent thoracic thin-section multislice CT scan and 1.5T MRI. A total of 437 regions-of-interest (ROIs) were classified at CT as advanced, moderate or mild alterations. Based on multi-echo single-shot TSE sequence acquired at five echo times, with breath-holding at end-expiration and ECG-triggering, entire lung T2 and PD maps were generated from each subject. The T2 relaxation time and the respective signal intensity were quantified by performing a ROI measurement on the T2 and PD maps in the corresponding CT selected areas of the lung. RESULTS: UIP and NSIP regional patterns could not be differentiated by T2 relaxation times or PD values alone. Overall, a strong positive correlation was found between T2 relaxation and PD in NSIP, r = 0.64, p<0.001; however, this correlation was weak in UIP, r = 0.20, p = 0.01. T2 relaxation showed significant statistical difference between active-inflammatory and stable-fibrotic NSIP regions at all levels, p<0.05, while for the analysis of ventral lesions PD proved no statistical difference, p>0.05. CONCLUSIONS: T2 relaxation times and PD values may provide helpful quantitative information for differentiating NSIP from UIP pattern. These parameters have the potential to differentiate active-inflammatory and stable-fibrotic lesions in NSIP.

MRI as indicator of pulmonary tuberculosis activity: from morphological to molecular level assessment - a case report.

We present the case of an adult patient with active post-primary pulmonary tuberculosis (TB) and discuss specific morphological and textural aspects found at high-field magnetic resonance imaging (MRI) of the lung. The 42-year-old man, heavy smoker, undertook a routine employment medical examination and was admitted to a referral pulmonology and TB center due to the abnormal findings seen on his chest radiography. The patient presented nonspecific symptoms, bilateral bronchial breath at pulmonary auscultation, inflammatory syndrome on the laboratory blood tests and positive sputum smears for acid-fast bacilli, which together with the typical aspect on the chest radiography lead to a diagnosis of post-primary pulmonary TB and administration of specific medication. To exclude a possible lung cancer and to reevaluate the extent of the disease, computed tomography and magnetic resonance imaging of the lung were performed. The magnetic resonance examination showed, with an accuracy similar to that of computed tomography, the morphology of active post-primary parenchymal TB lesions, as depicted on the T2-weighted acquisition. Moreover, the T1-weighted sequence using iterative decomposition allowed the assessment of both lipid and caseous pneumonia. To the best of our knowledge, this is the first reported case to assess post-primary pulmonary TB using high field MRI equipment, with an analysis from a morphological to a molecular level. By using a fast two-sequence protocol, both morphological, through T2-weighted acquisition, and textural information such as fat content, using dedicated T1-weighted sequence, can be obtained.

Morbidity by tuberculosis in the Jiu Valley: relation with diagnostic practice and the impact on therapeutic results.

BACKGROUND AND AIM: In the last two and a half decades the dynamics of tuberculosis has been modelled by social and economic conditions, with consequences on the life style, and effects on the onset and evolution of the disease. The Jiu Valley is an area with social problems: mining, mines closing down and ceasing activity, poverty. We looked for a relationship between changes of life style in the Jiu Valley and the dynamics of tuberculosis. METHODS: We studied 528 patients who asked for medical services in different hospitals in the Jiu Valley between 2010-2013. We structurally characterized this group, we identified the characteristics of life style, and we assessed the health state, in particular the relation with tuberculosis. RESULTS: We found out that the quality of life was influenced by the health state, especially by tuberculous disease. Quality of life was influenced by the life style, professional factors and their long term consequences. The study evidenced a strong relationship between apparently very different factors such as life style, professional factors on one side and those characterizing tuberculosis. CONCLUSIONS: We report the first detailed epidemiological data on tuberculosis in an economically poor area, the Jiu Valley.

A case control study of risk factors associated with pulmonary tuberculosis in romania: experience at a clinical hospital of pneumology.

BACKGROUND AND AIM: Tuberculosis (TB) remains a major public health issue in Romania. The aim of the present study was to evaluate the potential demographic, socioeconomic and behavioral risk factors for TB among hospitalized patients in Romania. METHODS: This is a case-control study conducted between March 1st 2014 and March 30th 2015 at Leon Daniello Clinical Hospital of Pneumology, Cluj Napoca. A total of 150 TB patients defined as "cases" were matched for age, sex and county of residence to 150 controls selected from patients attending the same hospital with respiratory diseases other than TB. Data collection was obtained through patient interviews using a structured questionnaire. Factors potentially associated with TB infection were analyzed using univariate and multivariate logistic regression. RESULTS: Factors independently associated with TB were illiteracy (OR=2.42, 95% CI 1.09-5.37), unemployment (OR=2.08, 95% CI 1.23-3.53), low household income (OR=4.12, 95% CI 2.53-6.71), smoking (more than 20 cigarettes per day) (OR=2.12, 95% CI 1.20-3.74), poor knowledge of TB (OR=3.46, 95% CI 1.97-6.07), presence of TB patient in household (OR=4.35, 95% CI 1.42-13.36), prior TB treatment (OR=2.2, 95% CI 1.93-2.5) and diabetes (OR=3.32, 95% CI 1.36-8.08). CONCLUSION: This study provided useful information that might help to develop and adapt effective policies for TB control in Romania.

The impact of immune disturbances on the failure of antituberculosis treatment.

BACKGROUND AND AIM: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex, with an evolution and treatment outcome determined by the interaction between the mycobacterial and human genotypes. Various deficiencies of innate immune response starting from the first encounter of M. tuberculosis with lung cells endanger host infection control due to decreased triggering of cellular immune resistance and disturbed humoral immunity. Disturbed cell mediated immunity, known as the basic immune response in tuberculous infection, contributes to the deficient generation of central necrosis granuloma, consequently being responsible for severe clinical aspects and low final outcome. The tuberculosis patient's immune assessment is important before treatment initiation, for establishing the risk reduction measures and increasing success rate. MATERIAL AND METHODS: The immune study was conducted on 54 new pulmonary tuberculosis cases with treatment failure, 34 new pulmonary tuberculosis cases that successfully ended the treatment and 50 healthy group individuals. Immune assays performed were: blastic transformation of lymphocytes induced by different antigens, quantitatitve assessment of cellular immunity through CD4+ T cell and CD8+ T cell phenotyping, humoral immunity - through immunoglobulin isotyping, innate resistance - through phagocyte activity of neutrophils, the titter of anti-tuberculosis antibodies and the serum level of circulating immune complexes. Investigations were performed at the onset the treatment and at the end of intensive phase of the standard anti-tuberculosis treatment. RESULTS: Immune disturbances evidenced in patients with treatment failure were: important deficiencies of cellular immunity, hyperactivity of humoral immunity and deficiencies of innate immunity. High predictive value for treatment failure showed the indices: deficiency of T lymphocytes count (OR=62.5) and T helper count (OR=12.5), high level of circulating immune complexes (OR=9.801), deficiency of innate resistance (decreased phagocytating index OR=2.875). CONCLUSIONS: For increasing the treatment success rate, the study of immune disturbances must be performed before of antituberculosis treatment initiation, especially of cellular immunity for the early start of immune adaptive treatment.

The role of exogenous risk factors of antituberculosis treatment failure.

BACKGROUND AND AIM: The Republic of Moldova reports the highest incidence of tuberculosis and the lowest treatment success rate among European region countries. In most of the patients the antituberculosis treatment failure is correlated with social risk factors (low socio-economical state, epidemiological danger characteristics) and biological factors (young age, male sex, physiological conditions, associated diseases). Clinical factors (advanced forms of tuberculosis, chronic evolution, immune disturbances), therapeutic factors (treatment errors and interruptions, individualized regimens) and administrative factors (drug interruption in supply, suboptimal treatment quality) prevail in regions with defficient in health care delivery. The association of risk factors has a higher impact than the severity of one risk factor. The risk factor assessment is very important before initiation of the treatment, for establishing the plan of risk reduction measures for increasing the success rate. The aim of the study was to determine the impact of exogenous risk factors on antituberculosis treatment failure. METHODS: The study was conducted on 201 patients with pulmonary tuberculosis and treatment failure and 105 patients with pulmonary tuberculosis who successfully finished the antituberculosis treatment. Selected cases were investigated according national standards. RESULTS: The treatment failure occurred in patients belonging to socially disadvantaged groups, patients with harmful habits (alcohol abuse, drug use, active smoking), patients from infectious clusters. Migration, homelessness and detention releasing imperil the quality of treatment, thus predisposing to the treatment failure. Social, educational support and the substitutive therapy and withdrawal techniques (tobacco, alcohol, psycho-active substances) must be implemented in the high risk groups in order to diminish the risk of treatment failure and to increase the treatment success rate. CONCLUSIONS: The study of exogenous risk factors in vulnerable groups will contribute to the precocious detection of patients predisposed to failing the tuberculosis treatment and will permit the initiation of measures centered on patient that will favor the increase of treatment quality and success rate.

State of the art in the diagnosis and management of interstitial lung disease.

The interstitial lung diseases (ILDs) are a diverse group of disorders characterized by a varying combination of inflammation and fibrosis of the pulmonary parenchyma. Treatment and prognosis of ILD typically depend on the underlying ILD subtype, highlighting the importance of accurate classification and diagnosis. Besides a thorough history and clinical examination, the protocol should include a 6-minute walk test, chest radiography, high-resolution computed tomography, biochemical analysis, pulmonary function tests, blood gas analysis, bronchoalveolar lavage, and, when necessary, a lung biopsy. The final diagnosis of ILD entities requires dynamic interaction between clinicians, radiologists and pathologists to reach a clinico-radiologic-pathologic diagnosis, the gold standard no longer being the histology but rather a multidisciplinary approach.

Evaluation of interleukin-10 levels in the plasma of patients with various stages of tuberculosis.

UNLABELLED: Mycobacterium tuberculosis (Mtb) infection remains one of the world's major causes of illness and mortality. A clear understanding of the host defense against Mtb is imperatively needed forthe control of this epidemic. When tuberculosis (TB) infection occurs, a variety of pro and anti-inflammatory cytokines play a vital role in the pathogenesis of this disease. Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines reported to suppress the protective immune response against tuberculosis. AIM: The aim of the present study was to evaluate the association of plasma IL-10 levels with various disease stages of TB and the possible effects of treatment on these levels. MATERIALS AND METHODS: A group of 30 patients with active pulmonary TB and a control group of 21 healthy individuals were enrolled in this study. The levels of IL-10 were measured before, during, and after treatment using commercially available enzyme-linked immune-sorbent assay (ELISA). Data were analyzed using GraphPad Prism version 5.0. RESULTS: The results showed that the levels of IL-10 had significant differences between the TB and control groups (p<0.05). The patients with abnormal chest X-Ray findings had higher IL-10 levels when compared to patients with normal X-Rays (p=0.03). A subgroup of 18 patients were followed during the treatment and the mean plasma concentration of IL-10 in patients before therapy was higher than in patients at 3 months of therapy and in patients after 6 months of therapy (p=0.01). However, the IL-10 level remained significantly higher in patients at the end of treatment compared with controls. These findings could be used in follow-up as clinical biomarker of the success of tuberculosis therapy.