Economic Impact and Clinical Outcomes of Omalizumab Add-On Therapy for Patients with Severe Persistent Asthma: A Real-World Study.

BACKGROUND: Omalizumab is a fully humanized monoclonal antibody indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma. AIMS: The aim of this study was to evaluate social, healthcare expenditure and clinical outcomes changes after incorporating omalizumab into standard treatment in the control of severe asthma. METHODS: In this multicentre retrospective study, a total of 220 patients were included from 15 respiratory medicine departments in the regions of Andalusia and Extremadura (Spain). Effectiveness was calculated as a 3-point increase in the Asthma Control Test (ACT) and a reduction in the annual number of exacerbations. The economic evaluation included both direct and indirect costs. Incremental cost-effectiveness ratio (ICER) was calculated. Results from the year before and the year after incorporation of omalizumab were compared. RESULTS: After adding omalizumab, improvement of lung function, asthma and rhinitis according to patient perception, as well as the number of exacerbations and asthma control measured by the ACT score were observed. Globally, both healthcare resources and pharmacological costs decreased after omalizumab treatment, excluding omalizumab cost. When only direct costs were considered, the ICER was €1712 (95% CI 1487-1995) per avoided exacerbation and €3859 (95% CI 3327-4418) for every 3-point increase in the ACT score. When both direct and indirect costs were considered, the ICER was €1607 (95% CI 1385-1885) for every avoided exacerbation and €3555 (95% CI 3012-4125) for every 3-point increase. CONCLUSIONS: Omalizumab was shown to be an effective add-on therapy for patients with persistent severe asthma and allowed reducing key drivers of asthma-related costs.

Pneumonia presenting with organ dysfunctions: Causative microorganisms, host factors and outcome.

Community-acquired pneumonia (CAP) is a serious infection that may occasionally rapidly evolve provoking organ dysfunctions. We aimed to characterize CAP presenting with organ dysfunctions at the emergency room, with regard to host factors and causative microorganisms, and its impact on 30-day mortality. 460 of 4070 (11.3%) CAP patients had ≥2 dysfunctions at diagnosis, with a 30-day mortality of 12.4% vs. 3.4% in those with one or no dysfunctions. Among them, the most frequent causative microorganisms were Streptococcus pneumoniae, gram-negatives and polymicrobial etiology. Independent host risk factors for presenting with ≥2 dysfunctions were: liver (OR 2.97) and renal diseases (OR 3.91), neurological disorders (OR 1.86), and COPD (OR 1.30). Methicillin-resistant Staphylococcus aureus (OR 6.41) and bacteraemic episodes (OR 1.68) had the higher independent risk among microorganisms. The number of organ dysfunctions vs. none increased at 30-day mortality: three organs (OR 11.73), two organs (OR 4.29), and one organ (OR 2.42) whereas Enterobacteria (OR 3.73) were also independently related to mortality. The number of organ dysfunctions was the strongest 30-day mortality risk factor while Enterobacteriaceae was also associated with poorer outcome. The assessment of organ dysfunctions in CAP should be implemented for management, allocation and treatment decisions on initial evaluation.

Age-related risk factors for bacterial aetiology in community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the effect of age and comorbidities, smoking and alcohol use on microorganisms in patients with community-acquired pneumonia (CAP). METHODS: A prospective multicentre study was performed with 4304 patients. We compared microbiological results, bacterial aetiology, smoking, alcohol abuse and comorbidities in three age groups: young adults (<45 years), adults (45-64 years) and seniors (>65 years). RESULTS: Bacterial aetiology was identified in 1522 (35.4%) patients. In seniors, liver disease was independently associated with Gram-negative bacteria (Haemophilus influenzae and Enterobacteriaceae), COPD with Pseudomonas aeruginosa (OR = 2.69 (1.46-4.97)) and Staphylococcus aureus (OR = 2.8 (1.24-6.3)) and neurological diseases with S. aureus. In adults, diabetes mellitus (DM) was a risk factor for Streptococcus pneumoniae and S. aureus, and COPD for H. influenzae (OR = 3.39 (1.06-10.83)). In young adults, DM was associated with S. aureus. Smoking was a risk factor for Legionella pneumophila regardless of age. Alcohol intake was associated with mixed aetiology and Coxiella burnetii in seniors, and with S. pneumoniae in young adults. CONCLUSION: It should be considered that the bacterial aetiology may differ according to the patient's age, comorbidities, smoking and alcohol abuse. More extensive microbiological testing is warranted in those with risk factors for infrequent microorganisms.

Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia.

BACKGROUND: Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP). OBJECTIVE: To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP. RESULTS: We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07-1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50-2.04) and renal disease (OR, 1.57; 95% CI, 1.21-2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52-0.73). Bacteremia (OR, 1.37; 95% CI, 1.05-1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31-1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10-2.49) were associated with severe sepsis CAP. CONCLUSIONS: CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.

Sensitivity, Specificity, and Positivity Predictors of the Pneumococcal Urinary Antigen Test in Community-Acquired Pneumonia.

RATIONALE: Detection of the C-polysaccharide of Streptococcus pneumoniae in urine by an immune-chromatographic test is increasingly used to evaluate patients with community-acquired pneumonia. OBJECTIVES: We assessed the sensitivity and specificity of this test in the largest series of cases to date and used logistic regression models to determine predictors of positivity in patients hospitalized with community-acquired pneumonia. METHODS: We performed a multicenter, prospective, observational study of 4,374 patients hospitalized with community-acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: The urinary antigen test was done in 3,874 cases. Pneumococcal infection was diagnosed in 916 cases (21%); 653 (71%) of these cases were diagnosed exclusively by the urinary antigen test. Sensitivity and specificity were 60 and 99.7%, respectively. Predictors of urinary antigen positivity were female sex; heart rate≥125 bpm, systolic blood pressure<90 mm Hg, and SaO2<90%; absence of antibiotic treatment; pleuritic chest pain; chills; pleural effusion; and blood urea nitrogen≥30 mg/dl. With at least six of all these predictors present, the probability of positivity was 52%. With only one factor present, the probability was only 12%. CONCLUSIONS: The urinary antigen test is a method with good sensitivity and excellent specificity in diagnosing pneumococcal pneumonia, and its use greatly increased the recognition of community-acquired pneumonia due to S. pneumoniae. With a specificity of 99.7%, this test could be used to direct simplified antibiotic therapy, thereby avoiding excess costs and risk for bacterial resistance that result from broad-spectrum antibiotics. We also identified predictors of positivity that could increase suspicion for pneumococcal infection or avoid the unnecessary use of this test.

Tobacco smoking increases the risk for death from pneumococcal pneumonia.

BACKGROUND: Active smoking increases the risk of developing community-acquired pneumonia (CAP) and invasive pneumococcal disease, although its impact on mortality in pneumococcal CAP outcomes remains unclear. The aim of this study was to investigate the influence of current smoking status on pneumococcal CAP mortality. METHODS: We performed a multicenter, prospective, observational cohort study in 4,288 hospitalized patients with CAP. The study group consisted of 892 patients with pneumococcal CAP: 204 current smokers (22.8%), 387 nonsmokers (43.4%), and 301 exsmokers (33.7%). RESULTS: Mortality at 30 days was 3.9%: 4.9% in current smokers vs 4.3% in nonsmokers and 2.6% in exsmokers. Current smokers with CAP were younger (51 years vs 74 years), with more alcohol abuse and fewer cardiac, renal, and asthma diseases. Current smokers had lower CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) scores, although 40% had severe sepsis at diagnosis. Current smoking was an independent risk factor (OR, 5.0; 95% CI, 1.8-13.5; P = .001) for 30-day mortality of pneumococcal CAP after adjusting for age (OR, 1.06; P = .001), liver disease (OR, 4.5), sepsis (OR, 2.3), antibiotic adherence to guidelines, and first antibiotic dose given < 6 h. The independent risk effect of current smokers remained when compared only with nonsmokers (OR, 4.0; 95% CI, 1.3-12.6; P = .015) or to exsmokers (OR, 3.9; 95% CI, 1.09-4.95; P = .02). CONCLUSIONS: Current smokers with pneumococcal CAP often develop severe sepsis and require hospitalization at a younger age, despite fewer comorbid conditions. Smoking increases the risk of 30-day mortality independently of tobacco-related comorbidity, age, and comorbid conditions. Current smokers should be actively targeted for preventive strategies.

Compliance with guidelines-recommended processes in pneumonia: impact of health status and initial signs.

Initial care has been associated with improved survival of community-acquired pneumonia (CAP). We aimed to investigate patient comorbidities and health status measured by the Charlson index and clinical signs at diagnosis associated with adherence to recommended processes of care in CAP. We studied 3844 patients hospitalized with CAP. The evaluated recommendations were antibiotic adherence to Spanish guidelines, first antibiotic dose <6 hours and oxygen assessment. Antibiotic adherence was 72.6%, first dose <6 h was 73.4% and oxygen assessment was 90.2%. Antibiotic adherence was negatively associated with a high Charlson score (Odds ratio [OR], 0.91), confusion (OR, 0.66) and tachycardia ≥100 bpm (OR, 0.77). Delayed first dose was significantly lower in those with tachycardia (OR, 0.75). Initial oxygen assessment was negatively associated with fever (OR, 0.61), whereas tachypnea ≥30 (OR, 1.58), tachycardia (OR, 1.39), age >65 (OR, 1.51) and COPD (OR, 1.80) were protective factors. The combination of antibiotic adherence and timing <6 hours was negatively associated with confusion (OR, 0.69) and a high Charlson score (OR, 0.92) adjusting for severity and hospital effect, whereas age was not an independent factor. Deficient health status and confusion, rather than age, are associated with lower compliance with antibiotic therapy recommendations and timing, thus identifying a subpopulation more prone to receiving lower quality care.

[Comparison of the Asthma Control Test (ACT) with lung function, levels of exhaled nitric oxide and control according to the Global Initiative for Asthma (GINA)]. / Relación del test de control del asma (ACT) con la función pulmonar, niveles de óxido nítrico exhalado y grados de control según la Iniciativa Global para el Asma (GINA).

INTRODUCTION: The current goal of asthma treatment is to achieve and maintain control. This study aimed to explore the relationship between the ACT (Asthma Control Test) questionnaire and the levels of control according to GINA (Global Initiative for Asthma) to establish the cut-off points for the ACT and evaluate its relationship with lung function and fractionated exhaled nitric oxide level (FeNO). PATIENTS AND METHODS: A multi-centre prospective study including 441 patients followed up in an outpatient Chest Clinic. A clinical protocol was followed, and FeNO, spirometry and ACT performed. Disease was classified according to levels of control using GINA. The study analysed sensitivity, specificity and area under the curve (ROC), and the ACT cut-off points. We studied the differences between the functional parameters and FeNO between levels of control. RESULTS: For controlled asthma the cut-off obtained was ACT> or =21 (area under the curve 0.791) and for uncontrolled < or =18 (AUC 0.774). We found significant differences in FeNO levels and pulmonary function among ACT> or =21 and ACT< or =18, although only 26.3% of patients with ACT< or =18 had a FEV1 <80% and 40% higher FeNO (> or =35 ppb). We found a correlation between baseline FEV1 and ACT (r=0.19, P<0.01) and between ACT and FeNO (r=-0.16, P<0.01). CONCLUSIONS: The cut-off points would be, for controlled asthma ACT> or =21, partly controlled asthma ACT=19-20 and uncontrolled asthma ACT< or =18. A more complete assessment would require including monitoring operating parameters and FeNO.

Relación del test de control del asma (ACT) con la función pulmonar, niveles de óxido nítrico exhalado y grados de control según la Iniciativa Global para el Asma (GINA) / Comparison of the Asthma Control Test (ACT) with Lung Function, Levels of Exhaled Nitric Oxide and Control According to the Global Initiative for Asthma (GINA)

Introducción. El objetivo actual en el tratamiento del asma es conseguir y mantener el control. Este estudio tiene como objetivos estudiar la relación entre el cuestionario ACT (Asthma Control Test) y los niveles de control según Global Initiative for Asthma para establecer los puntos de corte del ACT y evaluar su relación con la función pulmonar y la Fracción exhalada de óxido nítrico (FeNO). Pacientes y métodos. Estudio prospectivo multicéntrico con inclusión de 441 pacientes seguidos en consultas externas de neumología. Se realizó protocolo clínico, FeNO, espirometría forzada y ACT. Se clasificó la enfermedad según los niveles de control de la Global Initiative for Asthma. Se realizó estudio de sensiblidad, especificidad y área bajo la curva (ROC), estimándose los puntos de corte de ACT. Se estudiaron las diferencias entre los parámetros funcionales y FeNO entre los niveles de control. Resultados. Para el asma controlada el punto de corte obtenido fue ACT≥21 (área bajo la curva 0,791) y para el no controlada fue ≤18 (área bajo la curva 0,774). Encontramos diferencias significativas en niveles de FeNO y función pulmonar entre ACT≥21 y ACT≤18, aunque solo el 26,3% de pacientes con ACT≤18 presentaron un FEV1<80% y el 40% FeNO elevado (≥35 ppb). Encontramos correlación entre FEV1 basal y ACT (r=0,19, p<0,01), así como entre ACT y FeNO (r=−0,16, p<0,01). Conclusiones. Los puntos de corte para el asma controlada serían ACT≥21, para el asma parcialmente controlada ACT=19–20 y para el asma no controlada ACT≤18. Una valoración más completa del control requeriría incluir parámetros funcionales y FeNO.(AU)

Introduction. The current goal of asthma treatment is to achieve and maintain control. This study aimed to explore the relationship between the ACT (Asthma Control Test) questionnaire and the levels of control according to GINA (Global Initiative for Asthma) to establish the cut-off points for the ACT and evaluate its relationship with lung function and fractionated exhaled nitric oxide level (FeNO). Patients and methods. A multi-centre prospective study including 441 patients followed up in an outpatient Chest Clinic. A clinical protocol was followed, and FeNO, spirometry and ACT performed. Disease was classified according to levels of control using GINA. The study analysed sensitivity, specificity and area under the curve (ROC), and the ACT cut-off points. We studied the differences between the functional parameters and FeNO between levels of control. Results. For controlled asthma the cut-off obtained was ACT≥21 (area under the curve 0.791) and for uncontrolled ≤18 (AUC 0.774). We found significant differences in FeNO levels and pulmonary function among ACT≥21 and ACT≤18, although only 26.3% of patients with ACT≤18 had a FEV1 <80% and 40% higher FeNO (≥35 ppb). We found a correlation between baseline FEV1 and ACT (r=0.19, P<0.01) and between ACT and FeNO (r=−0.16, P<0.01). Conclusions. The cut-off points would be, for controlled asthma ACT≥21, partly controlled asthma ACT=19–20 and uncontrolled asthma ACT≤18. A more complete assessment would require including monitoring operating parameters and FeNO. (AU)

[Predictive value of chest X-ray and electrocardiographic abnormalities in patients with pulmonary embolism in relation to mortality and recurrences]. / Papel de las alteraciones radiográficas y del electrocardiograma en la predicción de mortalidad y recidivas en pacientes con embolia de pulmón.

BACKGROUND AND OBJECTIVE: Radiological and electrocardiographic (EKG) abnormalities are very frequent in patients with pulmonary embolism (PE). Our main objective was to evaluate, in patients with PE, whether any of those abnormalities was correlated with an increased risk of relapses or mortality until 3 months after the acute episode. PATIENTS AND METHOD: Multicenter observational study of patients included in the Venous Thromboembolic Disease Register (RIETE). Demographic, clinical, radiological and EKG data were collected from all patients. Statistics was made with the Pearson correlation and multiple linear regression analysis. RESULTS: We found a significant but non determinant association between mortality and the presence of radiological and/or EKG abnormalities and no relation between them and relapses of PE. CONCLUSIONS: Radiological or EKG manifestations could not predict relapses or mortality 3 months after PE in our patients.

Papel de las alteraciones radiográficas y del electrocardiograma en la predicción de mortalidad y recidivas en pacientes con embolia de pulmón / Predictive value of chest X-ray and electrocardiographic abnormalities in patients with pulmonary embolism in relation to mortality and recurrences

Fundamento y objetivo: es sabido que las alteraciones radiológicas y electrocardiográficas son muy frecuentes y diversas en los pacientes con embolia de pulmón (EP), pero se desconoce si pueden ser factores pronósticos a largo plazo (hasta los 3 meses). El objetivo principal del presente estudio ha sido evaluar si las alteraciones en la radiografía de tórax y en el electrocardiograma (ECG) podrían predecir la aparición de recidivas o la muerte en esta enfermedad. Pacientes y método: se ha realizado un estudio observacional y multicéntrico de pacientes diagnosticados de EP incluidos en el Registro Informatizado de la Enfermedad Tromboembólica venosa en España (RIETE). Se recogieron las variables demográficas, clínicas y exploratorias incluidas en el registro. Se aplicó un test de correlación de Pearson para averiguar la relación entre las variables, y con las variables significativas encontradas se realizó una regresión lineal múltiple, y se evaluaron las ecuaciones de predicción según supuestos de independencia, homocedasticidad y normalidad. Resultados: los hallazgos de la radiografía y el ECG se asociaron con la mortalidad por EP, pero ninguno de ellos fue determinante en el fallecimiento de los pacientes. No se encontró relación alguna entre estas variables y la aparición de recidivas. Conclusiones: la aparición o el tipo de alteraciones en la radiografía de tórax y el ECG no constituyeron factores predictivos de recidivas o de mortalidad en los primeros 3 meses del episodio agudo de EP (AU)

Background and objective: Radiological and electrocardiographic (EKG) abnormalities are very frequent in patients with pulmonary embolism (PE). Our main objective was to evaluate, in patients with PE, whether any of those abnormalities was correlated with an increased risk of relapses or mortality until 3 months after the acute episode. Patients and method: Multicenter observational study of patients included in the Venous Thromboembolic Disease Register (RIETE). Demographic, clinical, radiological and EKG data were collected from all patients. Statistics was made with the Pearson correlation and multiple linear regression analysis. Results: We found a significant but non determinant association between mortality and the presence of radiological and/or EKG abnormalities and no relation between them and relapses of PE. Conclusions: Radiological or EKG manifestations could not predict relapses or mortality 3 months after PE in our patients (AU)

Guidelines for the treatment of community-acquired pneumonia: predictors of adherence and outcome.

RATIONALE: Some studies highlight the association of better clinical responses with adherence to guidelines for empiric treatment of community-acquired pneumonia (CAP), but little is known about factors that influence this adherence. OBJECTIVES: Our objectives were to identify factors influencing adherence to the guidelines for empiric treatment of CAP, and to evaluate the impact of adherence on outcome. METHODS: We studied 1,288 patients with CAP admitted to 13 Spanish hospitals. Collected variables included the patients' clinical and demographic data, initial severity of the disease, antibiotic treatment, and specialty and training status of the prescribing physician. MEASUREMENTS AND MAIN RESULTS: Adherence to guidelines was high (79.7%), with significant differences between hospitals (range, 47-97%) and physicians (pneumologists, 81%; pneumology residents, 84%; nonpneumology residents, 82%; other specialists, 67%). The independent factors related to higher adherence were hospital, physician characteristics, and initial high-risk class of Fine, whereas admission to intensive care unit decreased adherence. Seventy-four patients died (6.1%), and treatment failure was found in 175 patients (14.2%). After adjusting for Fine risk class, adherence to the guidelines was found protective for mortality (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.3-0.9) and for treatment failure (OR, 0.65; 95% CI, 0.5-0.9). Treatment prescribed by pneumologists and residents was associated with lower treatment failure (OR, 0.6; 95% CI, 0.4-0.9). CONCLUSIONS: Adherence to guidelines mainly depends on the hospital and the specialty and training status of prescribing physicians. Nonadherence was higher in nonpneumology specialists, and is an independent risk factor for treatment failure and mortality.

Reaching stability in community-acquired pneumonia: the effects of the severity of disease, treatment, and the characteristics of patients.

BACKGROUND: The natural history of the resolution of infectious parameters in patients with community-acquired pneumonia (CAP) is not completely known. The aim of our study was to identify those factors related to host characteristics, the severity of pneumonia, and treatment that influence clinical stability. METHODS: In a prospective, multicenter, observational study, we observed 1424 patients with CAP who were admitted to 15 Spanish hospitals. The main outcome variable was the number of days needed to reach clinical stability (defined as a temperature of or=90 mm Hg, and oxygen saturation >or=90% or arterial oxygen partial pressure of >or=60 mm Hg). RESULTS: The median time to stability was 4 days. A Cox proportional hazard model identified 6 independent variables recorded during the first 24 h after hospital admission related to the time needed to reach stability: dyspnea (hazard ratio [HR], 0.76), confusion (HR, 0.66), pleural effusion (HR, 0.67), multilobed CAP (HR, 0.72), high pneumonia severity index (HR, 0.73), and adherence to the Spanish guidelines for treatment of CAP (HR, 1.22). A second Cox model was performed that included complications and response to treatment. This model identified the following 10 independent variables: chronic bronchitis (HR, 0.81), dyspnea (HR, 0.79), confusion (HR, 0.61), multilobed CAP (HR, 0.84), initial severity of disease (HR, 0.73), treatment failure (HR, 0.31), cardiac complications (HR, 0.66), respiratory complications (HR, 0.77), empyema (HR, 0.57), and admission to the intensive care unit (HR, 0.57). CONCLUSIONS: Some characteristics of CAP are useful at the time of hospital admission to identify patients who will need a longer hospital stay to reach clinical stability. Empirical treatment that follows guidelines is associated with earlier clinical stability. Complications and treatment failure delay clinical stability.