Patient and Physician Perspectives on Asthma and Its Therapy in Romania: Results of a Multicenter Survey.

Background and Objectives: Patient's behaviours, attitudes and beliefs related to asthma and its treatment were shown to influence the adherence to therapy and the level of asthma control. This survey aimed to assess the level of asthma control and patient-reported behaviours, attitudes and expectations related to their disease in Romanian patients. Materials and Methods: This cross-sectional quantitative survey was performed in February-March 2019 and enrolled 70 specialist physicians experienced in asthma management and 433 asthma patients under their care. Results: Of the 433 patients enrolled, 19.4% had mild asthma, 60.5% moderate asthma and 20.1% severe asthma. For the previous 12 months, asthma symptoms, exacerbations and emergency room visits were common in the sample analysed, with significantly higher figures in severe asthma patients (p < 0.001). The most important treatment goal for asthma patients was participation in all activities of daily living, while for physicians this was preventing asthma exacerbations. The valuation of the treatment goals was different between patients with severe asthma and those with mild and moderate forms. Based on the patients' responses, 3 attitude clusters were identified: empowered savvy (36.5% of the patients), pessimistic non-compliers (43.2%), and anxious strugglers (20.3%). "Empowered savvy" had the lowest frequency of severe asthma, the highest adherence to maintenance therapy and the highest level of confidence in the effectiveness of asthma medication. The opposite of this attitude cluster is the "anxious strugglers", containing more patients with severe asthma, a higher score for worries about asthma therapy and better self-reported knowledge of their treatment, contrasting with a proportion of 25% taking maintenance therapy only when having breathing difficulties. Conclusion: Asthma control in Romania remains poor, with frequent exacerbations and hospitalizations. The differences in treatment goals found between patients and physicians and between different asthma severity groups suggest the need for more patient-centred approaches.

Predictors of outcome of noninvasive ventilation in severe COPD exacerbation.

BACKGROUND: Noninvasive ventilation (NIV) reduces the rate of endotracheal intubation (ETI) and overall mortality in severe acute exacerbation of COPD (AECOPD) with acute respiratory failure and is increasingly applied in respiratory intermediate care units. However, inadequate patient selection and incorrect management of NIV increase mortality. We aimed to identify factors that predict the outcome of NIV in AECOPD. Also, we looked for factors that influence ventilator settings and duration. METHODS: A prospective cohort study was undertaken in a respiratory intermediate care unit in an academic medical center between 2016 and 2017. Age, BMI, lung function, arterial pH and pCO2 at admission (t0), at 1-2 h (t1) and 4-6 h (t2) after admission, creatinine clearance, echocardiographic data (that defined left heart dysfunction), mean inspiratory pressure during the first 72 h (mIPAP-72 h) and hours of NIV during the first 72 h (dNIV-72 h) were recorded. Main outcome was NIV failure (i.e., ETI or in-hospital death). Secondary outcomes were in-hospital mortality, length of stay (LOS), duration of NIV (days), mIPAP-72 h, and dNIV-72 h. RESULTS: We included 89 patients (45 male, mean age 67.6 years) with AECOPD that required NIV. NIV failure was 12.4%, and in-hospital mortality was 11.2%. NIV failure was correlated with days of NIV, LOS, in-hospital mortality (p < 0.01), and kidney dysfunction (p < 0.05). In-hospital mortality was strongly associated with days of NIV (OR 1.27, 95%CI: 1.07-1.5, p < 0.01) and with FEV1 (p < 0.05). All other investigated parameters (including left heart dysfunction, dNIV-72 h, mIPAP-72 h, pH, etc.) did not influence NIV failure or mortality. dNIV-72 h and days of NIV were independent predictors of LOS (p < 0.01). Regarding the secondary outcomes, left heart dysfunction and pH at 1-2 h independently predicted NIV duration (dNIV-72 h, p < 0.01), while BMI and baseline pCO2 predicted NIV settings (mIPAP-72 h, p < 0.01). CONCLUSION: In-hospital mortality and NIV failure were not influenced by BMI, left heart dysfunction, age, nor by arterial blood gas values in the first 6 h of NIV. Patients with severe acidosis and left heart dysfunction required prolonged use of NIV. BMI and pCO2 levels influence the NIV settings in AECOPD regardless of lung function.

Risk assessment of tuberculosis in immunocompromised patients. A TBNET study.

RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. MEASUREMENTS AND MAIN RESULTS: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. CONCLUSIONS: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

Genetic and geographic influence on phenotypic variation in European sarcoidosis patients.

Introduction: Sarcoidosis is a highly variable disease in terms of organ involvement, type of onset and course. Associations of genetic polymorphisms with sarcoidosis phenotypes have been observed and suggest genetic signatures. Methods: After obtaining a positive vote of the competent ethics committee we genotyped 1909 patients of the deeply phenotyped Genetic-Phenotype Relationship in Sarcoidosis (GenPhenReSa) cohort of 31 European centers in 12 countries with 116 potentially disease-relevant single-nucleotide polymorphisms (SNPs). Using a meta-analysis, we investigated the association of relevant phenotypes (acute vs. sub-acute onset, phenotypes of organ involvement, specific organ involvements, and specific symptoms) with genetic markers. Subgroups were built on the basis of geographical, clinical and hospital provision considerations. Results: In the meta-analysis of the full cohort, there was no significant genetic association with any considered phenotype after correcting for multiple testing. In the largest sub-cohort (Serbia), we confirmed the known association of acute onset with TNF and reported a new association of acute onset an HLA polymorphism. Multi-locus models with sets of three SNPs in different genes showed strong associations with the acute onset phenotype in Serbia and Lublin (Poland) demonstrating potential region-specific genetic links with clinical features, including recently described phenotypes of organ involvement. Discussion: The observed associations between genetic variants and sarcoidosis phenotypes in subgroups suggest that gene-environment-interactions may influence the clinical phenotype. In addition, we show that two different sets of genetic variants are permissive for the same phenotype of acute disease only in two geographic subcohorts pointing to interactions of genetic signatures with different local environmental factors. Our results represent an important step towards understanding the genetic architecture of sarcoidosis.

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement.

Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-γ based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking.

Obesity and Infection: What Have We Learned From the COVID-19 Pandemic.

Objective: The critical role played by the nutritional status in the complications, duration of hospitalization and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has emerged from several research studies in diverse populations. Obesity has been associated with an increased risk of serious complications, as the adipose tissue appears to have significant effects on the immune response. The aim of this narrative review was to investigate the relationship between COVID-19 and obesity. Methods: We performed a review of papers in the English language derived from PubMed, Science Direct, and Web of Science. The primary outcomes investigated were the severity of the disease, admission to the intensive care unit (ICU), need for intubation, and mortality. Results and Conclusion: Review of 44 eligible studies from 18 countries around the world revealed evidence that obesity increases the risk of severe COVID-19 complications, ICU admission, intubation and mortality. Patients with a higher body mass index (BMI) appear to be more vulnerable to SARS-CoV-2 infection, with more severe illness requiring admission to ICU and intubation, and to have higher mortality. A healthy body weight should be targeted as a long-term prevention measure against acute complications of infection, and in the event of COVID-19, overweight and obese patients should be monitored closely.

Esophageal Pressure Measurement in Acute Hypercapnic Respiratory Failure Due to Severe COPD Exacerbation Requiring NIV-A Pilot Safety Study.

Esophageal pressure (Pes) measurements could optimise ventilator parameters in acute respiratory failure (ARF) patients requiring noninvasive ventilation (NIV). Consequently, the objectives of our study were to evaluate the safety and accuracy of applying a Pes measuring protocol in ARF patients with AECOPD under NIV in our respiratory intermediate care unit (RICU). An observational cohort study was undertaken. The negative inspiratory swing of Pes (ΔPes) was measured: in an upright/supine position in the presence/absence of NIV at D1 (day of admission), D3 (3rd day of NIV), and DoD (day of discharge). A digital filter for artefact removal was developed. We included 15 patients. The maximum values for ∆Pes were recorded at admission (mean ∆Pes 23.2 cm H2O) in the supine position. ∆Pes decreased from D1 to D3 (p < 0.05), the change being BMI-dependent (p < 0.01). The addition of NIV decreased ∆Pes at D1 and D3 (p < 0.01). The reduction of ∆Pes was more significant in the supine position at D1 (8.8 cm H2O, p < 0.01). Under NIV, ∆Pes values remained higher in the supine versus upright position. Therefore, the measurement of Pes in AECOPD patients requiring NIV can be safely done in an RICU. Under NIV, ∆Pes reduction is most significant within the first 24 h of admission.

The Challenging Diagnosis of Interstitial Lung Disease in Children-One Case Report and Literature Review.

Childhood interstitial lung disease (chILD) includes a heterogeneous spectrum of rare respiratory disorders in children associated with substantial morbi-mortality. Interstitial tissue, and other pulmonary structures, epithelium, blood vessels, or pleura are involved, resulting in a restrictive lung disfunction. Respiratory symptoms set in progressively and are often subtle, making thorough clinical history and physical examination fundamental. The etiology often is obscure. The clinical presentation mimics pneumonia or asthma, leading to a diagnostic delay. Challenging diagnosis may require genetic tests, bronchoalveolar lavage, or lung biopsy. Alongside general supportive therapeutic measures, anti-inflammatory, immunosuppressive or antifibrotic agents may be used, based on data derived from adult studies. However, if accurate diagnosis and treatment are delayed, irreversible chronic respiratory failure may ensue, impacting prognosis. The most frequent chILD is hypersensitivity pneumonitis (HP), although it is rare in children. HP is associated with exposure to an environmental antigen, resulting in inflammation of the airways. Detailed antigen exposure history and identification of the inciting trigger are the cornerstones of diagnostic. This article provides the current state of chILD, revealing specific features of HP, based on a clinical case report of a patient admitted in our clinic, requiring extensive investigations for diagnosis, with a favorable long-term outcome.

Mechanisms of allergen immunotherapy supporting its disease-modifying effect.

Allergen immunotherapy (AIT) is considered the only disease-modifying treatment available at present for allergic disorders. Its main benefits include improvement of symptoms, decreased need for pharmacotherapy, prevention of new sensitizations and sustained effect after AIT completion. The key pillars of AIT-induced tolerance include a shift from Th2 to Th1 response, an increase of regulatory T and B cells, pro-inflammatory effector cell downregulation and IgE suppression, in addition to IgG4, IgA and IgD induction. AIT may also induce trained immunity, characterized by a durable decrease in group 2 of innate lymphoid cells (ILCs) and increased ILC1 and ILC3s. Understanding the immune mechanisms of AIT is essential for validating biomarkers for the prediction of AIT response and for achieving AIT success.

In the last decades, allergic diseases have become a public health concern worldwide. Currently, their treatment is mainly based on medications that control the symptoms or decrease future disease risk. The only disease-modifying treatment available for allergic diseases is allergen immunotherapy (AIT). Its main benefits include improvement of symptoms, prevention of new sensitizations and sustained effect after therapy completion. The allergen tolerance induced by AIT is explained by an increase in the number of regulatory immune cells, which reduce inflammation, and a progressive decrease in pro-inflammatory immune cells and IgE synthesis. Better understanding of the mechanisms of AIT is essential for improving efficacy and safety.

Infection and reinfection with SARS-CoV-2 in cancer patients: A cohort study.

COVID-19 reinfection, although a controversial issue, is an important clinical problem in cancer patients and beyond. The present study aimed to identify the risk factors associated with worse outcomes in cancer patients with Covid-19 in both first infection and reinfection and to describe the involvement of vaccines in reinfection outcome. The present study enrolled 85 patients with solid tumors who had Covid-19 infection and had not been previously vaccinated. Classical risk factors associated with worse outcomes in cancer patients with second SARS-Cov infection were considered. The patients were followed up retrospectively, measuring mortality at the first and second infection and the vaccination rate after the first infection. The factors associated with the highest risk of mortality at the first infection were, in order of importance: intensive care unit (ICU) admission, unfavorable performance status, radiologically quantifiable presence of oncological disease, and administration of cytotoxic chemotherapy in the period immediately before infection. The risk factors associated with higher mortality from reinfection were ECOG 3-4 performance status and administration of cytotoxic chemotherapy in the period immediately before infection. In the studied patients, mortality from reinfection was not affected by prior vaccination. Thus, bearing in mind all of these risk factors for poor outcomes in cancer patients with solid tumors presenting with Covid-19 can help the treating oncologists make personalized decisions about patient care during the pandemic.

Omalizumab for successful chemotherapy desensitisation: What we know so far.

BACKGROUND: Hypersensitivity reactions induced by chemotherapeutic drugs may influence the course of the oncologic disease by preventing doctors from prescribing first-line therapy. In order to prevent another hypersensitivity reaction to the culprit chemotherapeutic agent, the physician can decide between two possibilities: premedication or desensitisation protocols. Rapid drug desensitisation showed successful results for most patients, but some of them may develop symptoms. Although omalizumab is not licensed as premedication or adjuvant therapy in chemotherapy desensitisation protocols, there have been published some case reports and small sample size studies that indicated promising results. METHODS: We reviewed all the published literature regarding the use of omalizumab during chemotherapy desensitisation protocols. RESULTS AND CONCLUSIONS: We found a great heterogeneity between the doses and the interval between omalizumab injections and chemotherapy - rapid drug desensitisation, but most of the studies showed promising results. As a corollary, we propose a dose regimen of omalizumab administered before the first desensitisation protocol. Then, omalizumab should be administered one day before every chemotherapy regimen. Omalizumab might be used as an adjuvant therapy and might be a solution for a hopeless situation.

Plasticity of regulatory T cells under cytokine pressure.

CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-bet, GATA3, Runx 1, NFAT, etc.) also controlled by cytokines, in modulating the Th phenotype and functions. In this review, we analyze the plasticity of Treg population focusing on the most recent discoveries on how microenvironmental cytokines refine/modify Treg phenotype and function, thus changing their fate.

Predictors of Long-term Mortality after Hospitalization for Severe COPD Exacerbation.

Introduction:Chronic obstructive pulmonary disease (COPD) is a global health problem resulting in significant morbidity. Acute exacerbation of COPD (AECOPD) is a severe complication associated with increased short- and long-term mortality. Identifying predictors of long-term mortality after a severe AECOPD may improve management and long-term outcome of this disease. Materials and methods:A two-year prospective cohort study was undertaken in an academical medical center between 2016 and 2018. Patients with severe AECOPD who required non-invasive ventilation (NIV) were included. Baseline characteristics at inclusion, comorbidities (kidney dysfunction, left heart disease, diabetes), number of prior episodes of AECOPD and indication for long-term oxygen therapy (LTOT) or non-invasive ventilation (LTNIV) were recorded. Patients were monitored for a two-year period after initial admission. Outcomes were six-month, one-year and two-year mortality, irrespective of cause. Outcomes:51 patients (31 male, mean age 68.1) were included in the study. Mortality rates at six months, one year and two years were 20, 26 and 36%, respectively. Patients receiving LTOT and LTNIV at discharge had lower mortality at two years versus patients with no indication for LTOT and LTNIV at discharge. Absence of LTOT increased six-month mortality (OR .2, 95% CI, .04 to .90) and one-year mortality (p<.05). FEV1 and BMI were also correlated with long-term mortality in univariate analysis, p<.05. Age, number of prior episodes of AECOPD or the presence of comorbidities had no influence on long-term mortality. Conclusion:After an episode of severe AECOPD, LTOT is associated with lower long-term mortality when compared to patients with no severe hypoxemia at discharge. A decreased lung function and body mass index increase long-term mortality.

[Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs): short update]. / Reactii de hipersensibilitate la antiinflamatorii nesteroidiene: scurta actualizare.

Hypersensitivity reactions to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are a challenge to the clinicians, due to their severity. In susceptible individuals, NSAIDs induce a wide spectrum of reactions with various timing and organ manifestations, involving immunological and non-immunological mechanisms. Diagnosis of hypersensitivity to NSAID is based on characteristic symptoms precipitated with ASA/NSAIDs. Oral challenge with NSAID is the "gold standard" for the diagnosis and can be performed in order to confirm hypersensitivity to the culprit drug or to confirm or exclude tolerance to an alternative drug. Diagnosis process includes understanding of the underlying mechanism, and is mandatory for prevention of future events.

Immediate and delayed hypersensitivity reactions to intravascular iodine based radiocontrast media -- an update.

Used since 1929 in medical practice, nowadays four chemical varieties of intravascular iodine based radiocontrast media (I-RCM) are available: ionic monomers with high osmolarity, ionic dimers with low osmolarity, non-ionic monomers with low osmolarity and non-ionic iso-osmolar dimers. Increasing prescription of l-RCMs augments the number of reported hypersensitivity reactions. I-RCM induced hypersensitivity reactions can be dclasified in two types: immediate hypersensitivity reactions (IHRs - occurring within the first hour) and delayed hypersensitivity reactions (DHRs - occurring between 1 hour and 7 days). IHRs usually present as urticaria and angioedema but may associate severe respiratory and cardiovascular symptoms. Risk factors for an IHRs include a prior immediate reaction, personal history of atopic diseases (mainly asthma) and treatment with beta blocking agents. Diagnostic tests for IHRs include blood tests (serum tryptase) and skin tests (prick and intradermal) performed 2 to 6 months after IHR. High osmolarity of the I-RCM is the factor most strongly associated with IHRs. Primary prevention of IHRs involves the use of non-ionic low-osmolar or iso-osmolar agents for all intravascular procedures. DHRs are usually mild to moderate in severity, transient and self-limiting, presenting as maculopapular rash in more than 50% of cases. As with IHRs, the most important risk factor for DHRs is a previous reaction to I-RCM. Assessment of DHRs includes skin prick tests, intradermal and patch tests. Due to extensive cross-reactivity between I-RCM, a change of product is no guarantee against a repeated reaction. Current premedication procedures in patients with previous severe reactions can reduce symptoms, but may not prevent recurrent reactions.

[Antibiotic resistance of S. pneumoniae and H. influenzae strains isolated from patients with community acquired respiratory tract infections. BACTRO multicenter, multidisciplinary study]. / Spectrul de rezistenta la antibiotice a tulpinilor de S. pneumoniae si H. influenzae izolate de la pacienti cu infectii comunitare de tract respirator. Studiul multicentric, multidisciplinar BACTRO.

UNLABELLED: Community respiratory tract infections are common in clinical practice. Antimicrobial treatment should be promptly administered and guided by a probabilistic approach according to the clinical presentation and local patterns of bacterial resistance. Bacterial resistance is widespread, with large geographical variations related to behaviors in antibiotics prescription. S. pneumoniae and H. influenzae are the most frequent pathogens responsible for respiratory tract infections etiology. METHODS: We assessed the antibiotics susceptibility of S. pneumoniae and H. influenzae strains isolated from patients with community respiratory tract infections, prospectively enrolled over a period of 3 consecutive years, by determining the MIC. Analysis was performed using both cutoffs provided by European Committee on Antimicrobial Susceptibility testing (EUCAST) and CLSI. Consequently we evaluated the influence of different factors associated with the development of bacterial resistance. RESULTS: We analyzed 293 S. pneumoniae strains and 265 H. influenzae strains isolated during 1999-2001, mainly from sputum (68.3% and 74.9% respectively of total isolates). We observed a high proportion of S. pneumoniae resistant to penicillin (6.1% resistant and 48.5% with intermediate susceptibility) and to erythromycin (39% resistant strains). H. influenzae strains were resistant to amoxicillin in 26% of cases and the presence of betalactamase was certified in 13% of tested isolates; 18.3% of H. influenzae strains were resistant to amoxicillin through specific mechanisms other than by producing betalactamase. Other antibiotic resistances were assessed. CONCLUSIONS: In Romania clinician must consider the high prevalence of antibiotic resistance, particulary of S. pneumoniae to macrolides and beta-lactams (thus requiring the use of high doses of betalactams) and the high proportion of beta-lactamase producing H. influenzae.

Efficacy and safety of fluticasone and formoterol in a single pressurized metered dose inhaler.

BACKGROUND: Fluticasone and formoterol are well established medications for the treatment of asthma. This study (Clinicaltrials.gov identifier: NCT00734318) compares the efficacy and safety of a combination of these drugs in a single inhaler (fluticasone/formoterol) versus the individual components (fluticasone + formoterol). METHODS: Patients aged ≥ 18 years (n=620) with a history of severe, persistent reversible asthma for ≥ 6 months prior to screening were included in this randomized, double-blind study, which consisted of a screening phase of up to 5 days, a 2-week run-in phase and an 8-week treatment period. RESULTS: Fluticasone/formoterol (500/20 µg, b.i.d.) was at least as effective as fluticasone + formoterol (500 µg + 24 µg, b.i.d.) with respect to the primary outcome measure: there were similar increases in mean pre-morning dose forced expiratory volume in the first second (FEV(1)) in these two groups. Fluticasone/formoterol (500/20 µg, b.i.d.) also demonstrated similar efficacy to fluticasone + formoterol in terms of change in mean FEV(1) from baseline pre-morning dose to 2 h post-morning dose at week 8, as well as for several secondary parameters. Fluticasone/formoterol (500/20 µg, b.i.d.) demonstrated superiority to fluticasone monotherapy (500 µg, b.i.d.) and fluticasone/formoterol (100/10 µg, b.i.d.) for several secondary efficacy parameters. Fluticasone/formoterol had a similar safety and tolerability profile to fluticasone + formoterol. CONCLUSION: This study demonstrated that the fluticasone/formoterol combination is at least as effective as its components administered concurrently from separate inhalers. Fluticasone/formoterol (500/20 µg, b.i.d.) showed superior efficacy to its inhaled corticosteroid component alone and the efficacy of fluticasone/formoterol was dose-dependent for several clinically important parameters.

[Ways to quantify dyspnea severity. Part I. Baseline Dyspnea Index (BDI), Transition Dyspnea Index (TDI)]. / Modalitati de cuantificare a severitatii dispneii Partea I. Indexul de dispnee initial (BDI) si Indexul de tranzitie al dispneii (TDI).

Dyspnea is the major reason that patients with pulmonary diseases seek medical attention. In this paper we present the main scales used to evaluated dyspnea. We described in details the characteristics of Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI): ways of administration, domains, scores and minimally clinical important difference (MCID).