Impact of bedaquiline on treatment outcomes of multidrug-resistant tuberculosis in a high-burden country.

BACKGROUND: Evaluation of novel anti-tuberculosis (TB) drugs for the treatment of multidrug-resistant (MDR)-TB continues to be of high interest on the TB research agenda. We assessed treatment outcomes in patients with pulmonary MDR-TB who received bedaquiline-containing treatment regimens in the Republic of Moldova, a high-burden MDR-TB country. METHOD: We systematically analysed the SIMETB national electronic TB database and performed a retrospective propensity score-matched comparison of treatment outcomes in a cohort of patients with MDR-TB who started treatment during 2016-2018 with a bedaquiline-containing regimen (bedaquiline cohort) and a cohort of patients treated without bedaquiline (non-bedaquiline cohort). RESULTS: Following propensity score matching, 114 patients were assigned to each cohort of MDR-TB patients. Patients in the bedaquiline cohort had a higher 6-month sputum culture conversion rate than those in the non-bedaquiline cohort (66.7% versus 40.3%; p<0.001). Patients under bedaquiline-containing regimens had a higher cure rate assessed by both World Health Organization (WHO) and TBnet definitions (55.3% versus 24.6%; p=0.001 and 43.5% versus 19.6%; p=0.004, respectively), as well as a lower mortality rate (8.8% versus 20.2%; p<0.001 and 10.9% versus 25.2%; p=0.01, respectively). In patients who previously failed on MDR-TB treatment, >40% of patients achieved a cure with a bedaquiline-containing regimen. CONCLUSIONS: Bedaquiline-based MDR-TB treatment regimens result in better disease resolution when compared with bedaquiline-sparing MDR-TB treatment regimens under programmatic conditions in a country with a high burden of MDR-TB.

Chronic Obstructive Pulmonary Disease and Stroke.

Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the world and its incidence and prevalence is on the rise. It is evident that COPD is linked to cardiovascular disease. In the last years, several studies demonstrated that COPD may also be a risk factor for stroke, another major cause of death worldwide. Taking in consideration that COPD has multiple comorbidities it is hard to say whether COPD is an independent risk factor for stroke or it is due to confounding effect. This review is aimed to discuss current data on COPD and stroke, potential links, therapy, and prevention. Current data suggest that COPD may increase the risk of hemorrhagic stroke. The incidence of other stroke subtypes may also be increased in COPD or may be due to confounding effect. However, COPD patients who have stroke are at risk for pulmonary and extrapulmonary complications. We conclude that more studies are needed to further clarify the links between COPD and stroke. The management of COPD as well as the use of prevention therapy is essential to decrease the risk for stroke and should be at special attention in pulmonary medicine and neurology.

Predicting Health-Related Quality of Life in Patients with Chronic Obstructive Pulmonary Disease: The Impact of Age.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity in the elderly population. COPD leads to a reduced health-related quality of life (HRQL), but the factors which contribute to this are not well understood. A better understanding of the factors which determine HRQL should lead to an improved care for such patients. OBJECTIVES: The purpose of this study was to investigate possible age-related differences in HRQL in a population of patients with a similar severity of obstruction. METHODS: A total of 180 consecutive COPD patients were enrolled into the study. We analyzed spirometric data, BODE index and its components, and comorbidities were assessed by the Charlson index. HRQL was assessed by the Clinical COPD Questionnaire (CCQ) and St. George's Respiratory Questionnaire (SGRQ). RESULTS: The cohort consisted of 93 'younger' patients (mean age 54.8 ± 3.1 years) and 87 older patients (mean age 73.1 ± 5.5 years). Patients in both groups had a similar severity of obstruction: FEV1 (% from predicted) was 39.9 ± 13.2% in the elderly group compared to 41.7 ± 11.7% in the younger group (p > 0.05). The forward stepwise regression analysis shows that the BODE index, the Charlson index, and the rate of exacerbations are important predictors of deterioration of HRQL in elderly COPD patients, which explains 29% of the total SGRQ score. In the younger COPD patients, the coefficient of determination R2 was 0.27, but the predictors were the BODE index and the rate of exacerbations. CONCLUSIONS: The BODE index, the Charlson index, and the rate of exacerbations were found to be the major determinants of HRQL in elderly COPD patients, while in younger COPD patients, the BODE index and the rate of exacerbations were influential factors.

Multidimensional indices in the assessment of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a very common disease, is the third leading cause of death worldwide. Due to the significant heterogeneity of clinical phenotypes of COPD there is no single method suitable for predicting patients' health status and outcomes, and therefore multidimensional indices, assessing different components of the disease, were developed and are recommended for clinical practice by international guidelines. Several indices have been widely accepted: BODE and its modifications, ADO, DOSE, CODEX, COTE. They differ in their composition and aim, while they are more accurate and better validated in specific settings and populations. We review the characteristics, strengths and limitations of these indices, and we discuss their role in routine management of patients with COPD, as well as in specific clinical scenarios, such as resuscitation and ceiling of care, or decisions to offer more invasive treatments. This analysis may help clinicians to use those indexes in a more practical and appropriate way.

"Chronic obstructive pulmonary disease and phenotypes: a state-of-the-art."

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and multisystemic disease with progressive increasing morbidity and mortality. COPD is now widely accepted as a heterogeneous condition with multiple phenotypes and endotypes. This review will discuss the old and new concepts for the different types of COPD phenotypes, as well as the inclusion of them in current guidelines. Phenotypical approach to COPD is having huge impact on everyday practice and changed nonpharmacological and pharmacological management of COPD in last decade. However, phenotypical approach is small step to precision medicine in COPD management in the absence of big, specific and well-designed COPD trials with exact identification of phenotypes for more personalization of the treatment of COPD.

To sleep, or not to sleep - that is the question, for polysomnography.

Have we reached the point where respiratory polygraphy can replace polysomnography in the assessment of OSAS? http://ow.ly/UxCU30bNopq.

Williams-Beuren syndrome--a rare cause of recurrent hemoptysis.

Williams-Beuren syndrome (WBS) is a rare genetic disease with a distinctive constellation of clinical findings. The disease can be diagnosed clinically by a recognizable pattern of malformations, including cardiovascular malformations, a characteristic facial dysmorphism, as well as neurological and cognitive features. We present the case of a 23-years-old woman repeatedly admitted to Pulmonology Clinic for massive hemoptysis. Diagnosis of Williams-Beuren syndrome was revealed by clinical findings and confirmed by CT-angiography data of cardiovascular malformations and fluorescence in situ hybridization (FISH) genetic test. WBS is a multisystem disorder and usually is recognized by clinician. If clinical impression is not clearly consistent with WBS, FISH remains the most widely used test.

From smoking to COPD--current approaches.

Chronic obstructive pulmonary disease (COPD) remains a leading cause of death all over the world. Even though it is the most intensely studied disease induced by cigarette smoking there are still incomplete researches concerning its pathophysiology and treatment. So far it has been determined the deleterious effects of the secreted molecules diversity and some feasible therapies for their diminution. According to current studies more relevance gains the possible autoimmune origin of COPD and the epigenetic modifications. The idea of autoimmunity in smoking induced COPD began to be speculated with the discovery of autoantibodies in patient's serum, but there are some studies who consider antibody complexes that reside in the lung tissue as more relevant for future research. By developing the autoimmune aspect of COPD it will become possible to select more precise treatment strategies. The importance of epigenetic changes in this field might be appreciated starting with the fact of an existing connection between epigenetic modifications induced by maternal smoking and latter COPD development. This explains the tendency toward different drugs capable of restoring these transformations such as deacetylation agents expected also to prevent steroid resistance. Nevertheless smoking cessation remains as the indispensable approach for COPD treatment and prevention.

Prevalence and burden of comorbidities in Chronic Obstructive Pulmonary Disease.

The classical definition of Chronic Obstructive Pulmonary Disease (COPD) as a lung condition characterized by irreversible airway obstruction is outdated. The systemic involvement in patients with COPD, as well as the interactions between COPD and its comorbidities, justify the description of chronic systemic inflammatory syndrome. The pathogenesis of COPD is closely linked with aging, as well as with cardiovascular, endocrine, musculoskeletal, renal, and gastrointestinal pathologies, decreasing the quality of life of patients with COPD and, furthermore, complicating the management of the disease. The most frequently described comorbidities include skeletal muscle wasting, cachexia (loss of fat-free mass), lung cancer (small cell or non-small cell), pulmonary hypertension, ischemic heart disease, hyperlipidemia, congestive heart failure, normocytic anemia, diabetes, metabolic syndrome, osteoporosis, obstructive sleep apnea, depression, and arthritis. These complex interactions are based on chronic low-grade systemic inflammation, chronic hypoxia, and multiple common predisposing factors, and are currently under intense research. This review article is an overview of the comorbidities of COPD, as well as their interaction and influence on mutual disease progression, prognosis, and quality of life.

A rare genetic cause of bronchiectasis.

Bronchiectasis, defined as an abnormal and irreversible dilatation of the bronchi, frequently associated with inflammation, is the most common complication of recurrent infections. Effective pulmonary immunity is necessary to prevent chronic bronchial damage due to bacterial infection. Primary immune deficiencies comprise a heterogeneous group of genetically determined disorders that affect development and/or the function of innate or adaptive immunity. In multiple series reported in literature, common variable immunodeficiency (CVID), X-linked agammaglobulinemia (XLA) and chronic granulomatous disease (CGD) were the most common forms of primary immune deficiencies (PIDs) associated with bronchiectasis (1,15). Despite advances in the molecular knowledge of PIDs during the past two decades, there are many undiagnosed or late diagnosed patients (6,14). We report a case of Bruton's disease late diagnosed, already with bronchiectasis, with an early onset of recurrent respiratory infections.

The EMBARC European Bronchiectasis Registry: protocol for an international observational study.

Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age <18 years; and 3) patients who are unable or unwilling to provide informed consent. The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications. The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials.

Interstitial pneumonitis after treatment for hepatitis C virus infection.

Pulmonary toxicity is a rare side effect of interferon treatment with a wide spectrum of lung tissue conditions, including interstitial pneumonitis, pulmonary sarcoidosis, bronchiolitis obliterans organizing pneumonia, pleural effusion, exacerbation of bronchial asthma, reversible pulmonary hypertension and acute respiratory distress syndrome. We report a case of interstitial pneumonitis in a patient treated with pegylated interferon α2-a and ribavirin for chronic hepatitis C virus infection, genotype 1. The case was marked by progression of the respiratory symptoms even after the withdrawn of the pegylated interferon. One-year treatment with systemic corticosteroid ensured a considerable resorption of CT lesions but only a moderate improvement of symptoms and diffusion capacity without a complete recovery.

Predictors of daytime sleepiness in patients with obstructive sleep apnea.

BACKGROUND: The main symptomatic criterion to diagnose obstructive sleep apnea (OSA) is the level of daytime sleepiness. The Epworth Sleepiness Scale is a simple, self-administered questionnaire which provides a measurement of the subject's general level of daytime sleepiness. The aim of this study was to investigate the factors that can predict daytime sleepiness in patients with sleep apnea. METHODS: 50 consecutive patients with obstructive sleep apnea were enrolled into the study. Age, gender, anthropometric and polygraphic data were thoroughly analyzed. In all subjects daily sleepiness was assessed by Epworth Sleepiness Scale. RESULTS: The mean age of the subjects was 54.7 ± 12.8 years, 82% males. The mean BMI was 31.9 ± 6 kg/m2. Pearson correlation coefficient analysis demonstrates a significant positive correlation between the Epworth Sleepiness Scale and the desaturation index (r = 0.31, p < 0.01) and arterial hypertension (r = 0.32, p < 0.01). The forward stepwise regression analysis shows that the apnea hypopnea index and desaturation index are important predictors of daytime sleepiness in patients with obstructive sleep apnea which explains 40% of the Epworth Sleepiness Scale score. CONCLUSION: The desaturation index showed the strongest correlation with the Epworth scale. According to the results of the backward stepwise multiple regression and logistic regression, the predictors for the level of daytime sleepiness are oAHI and index of desaturation. According to the analysis of the ROC curve, desaturation index is a predictor of a high specificity.

[Cryptococcosis--a common fungal infection in immunosuppressed patient]. / Criptococoza--infectie fungica frecventa a imunocompromisululi.

Cryptococcus is a leading mycological cause of morbidity among HIV-infected patients. In many patients, cryptococcosis is the first indication of AIDS. The lung is invariably the portal of entry and initial site of infection for C. neoformans. In immunosuppressed patients all areas of the body can be infected, and central nervous sistem involvement is the most severe complication. Cryptococcosis is an important fungal infection thatshould be considered in the differential diagnosis of the pulmonary infiltrates in the immunosuppressed patient. The purpose of this paper is to review the current knowledge of the management and treatment strategies of cryptococcosis.

[Efficiency of prognostic scores for the assessment of patients with severe influenza pneumonias]. / Eficienta scorurilor prognostice în evaluarea pneumoniilor gripale severe.

AIM: To compare the efficiency of some prognostic scores in patients with severe influenza pneumonias. MATERIALS AND METHODS: The study was performed on a cohort of 75 cases of 2009 AH1N1 influenza associated pneumonias. Clinical and laboratory features at admission were used to calculate retrospectively the following prognostic scores: SCAP (Severe Community Acquired Pneumonia), CAP-PIRO (Community Acquired Pneumonia--Predisposition Infection Reaction, Organ failure), SMRT-CO (Systolic blood pressure, Multilobar infiltrates, Respiration rate, Tachycardia, Confusion, Oxygen), IDSA/ATS (Infectious Diseases Society of America/American Thoracic Society). The scores were used to assess two different outcomes--death and need for invasive mechanical ventilation (IMV). The performance of the prognostic tools were assessed using the area under receiver operating characteristic (AUC), and the sensitivity and specificity for identifying high risk patients for severe course of pneumonia. RESULTS: IMV was applied in 29 (38.7%) of studied cases, in 15 (20%) the diseases had a fatal outcome. Despite the fact that all scores had a very good discriminatory power in predicting both outcomes (AUC > 0,8), some of them have a very low sensitivity, in classes corresponding to sever pneumonias, in predicting mortality (IDSA/ATS-0%; 95% CI, 0-21.8%), as well as the need for IMV (IDSA/ATS-0%; 95% CI, 0-11.9%); SCAP-58.6% (95% CI, 38.9-76.5%); CAP-PIRO-58,6% (95% CI, 38.9-76.5%). CONCLUSIONS: The CAP-PIRO and SMRT-CO scores were found to have the best performances to predict death from influenza associated severe pneumonias and the last, also in predicting the need for IVM. Other analyzed scores underestimate the risk of occurrence of both assessed outcomes.

[Pulmonary epithelioid hemangioendothelioma--a case report]. / Hemangioendoteliom epitelioid pulmonar --prezentare de caz.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare soft tissue tumor of endothelial origin that occurs among young women and typically presents as bilateral multiple nodules, readily mistaken for carcinoma or, as in this case, Wegener's granulomatosis. This is a rare disease, with approximately 50 cases described in the literature. In the present report, we describe a case of PEH in a 39-yr-old woman. Immunohistochemically, the tumor cells were positive for CD34.