Inhaled Dry Powder Antibiotics in Patients with Non-Cystic Fibrosis Bronchiectasis: Efficacy and Safety in a Real-Life Study.

BACKGROUND: Nebulised antibiotics are habitually used in patients with bronchiectasis, but the use of dry powder inhaled antibiotics (DPIA) in these patients is extremely limited. This study seeks to analyse the efficacy and safety of DPIA in bronchiectasis patients. MATERIAL AND METHODS: Multi-centre study of historic cohorts. All the hospital centres in Spain were contacted in order to collect data on patients with a diagnosis of bronchiectasis who had taken at least one dose of DPIA. Its efficacy was analysed in clinical, functional and microbiological terms by comparing the year before and the year after the prescription of DPIA. Adverse effects and variables associated with these effects, or any need to withdraw the drug, were also analysed. RESULTS: 164 patients from 33 Spanish centres were included; 86% and 14% of these were treated with dry powder colistin and tobramycin, respectively. Chronic bronchial infection by Pseudomonas aeruginosa was present in 86% of these patients, and DPIA significantly reduced the number of exacerbations, the quantity and purulence of sputum and the isolation of pathogenic microorganisms. The most common adverse effect was cough (40%), particularly in cases of Chronic Obstructive Pulmonary Disease (COPD) and a previous cough and in those patients who had difficulties in handling the device. These factors were associated with a higher level of withdrawal of the treatment. There were no serious adverse effects. CONCLUSIONS: Our study suggests that DPIA are clinically efficacious and safe for treating bronchiectasis patients. Cough was shown to be the most common side-effect and reason for withdrawal of the treatment.

Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients.

BACKGROUND: Inhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD patients were used to compare the anti-inflammatory effects of aclidinium bromide (a long-acting muscarinic antagonist) with corticosteroids and their potential additive effect. METHODS: Human sputum and blood neutrophils were isolated from healthy individuals (n = 37), patients with stable COPD (n = 52) and those with exacerbated COPD (n = 16). The cells were incubated with corticosteroid fluticasone propionate (0.1 nM-1 µM), aclidinium bromide (0.1 nM-1 µM) or a combination thereof and stimulated with 1 µg of lipopolysaccharide/ml or 5 % cigarette smoke extract. Levels of the pro-inflammatory mediators interleukin-8, matrix metalloproteinase-9, CCL-5, granulocyte-macrophage colony-stimulating factor and interleukin-1ß were measured and the mechanisms of corticosteroid resistance evaluated at the end of the incubation. RESULTS: The non-neuronal cholinergic system was over-expressed in neutrophils from COPD patients, as evidenced by increases in the expression of muscarinic receptors (M2, M4 and M5), choline acetyltransferase and vesicular acetylcholine transporter. Aclidinium bromide demonstrated anti-inflammatory effects on neutrophils from COPD patients, reversing their resistance to corticosteroids. Additive effects of combined aclidinium bromide and fluticasone propionate in blocking M2 receptor levels, inhibiting phosphoinositide 3-kinase-δ and enhancing the glucocorticoid response element transcription factor were demonstrated and were accompanied by an increase in the corticosteroid-induced expression of anti-inflammatory-related genes. CONCLUSIONS: LAMAs potentiate the anti-inflammatory effects of corticosteroids in neutrophils from COPD patients in vitro, thus providing a scientific rationale for their use in combination with corticosteroids in the treatment of COPD.

Accuracy of PaO2 /FiO2 calculated from SpO2 for severity assessment in ED patients with pneumonia.

BACKGROUND AND OBJECTIVE: Assessment of oxygenation in patients with community-acquired pneumonia is critical for treatment. The accuracy of percutaneous oxygen saturation (SpO2 ) determined by pulse oximetry is uncertain, and it has limited value in patients receiving supplemental oxygen. We hypothesized that calculation of partial arterial oxygen concentration/inspired oxygen faction (PaO2 /FiO2 ) from SpO2 by the Ellis or Rice equations might adequately correlate with PaO2 /FiO2 measured by arterial blood gases. METHODS: We studied 1004 patients with pneumonia in the emergency department with simultaneous measurement of SpO2 and PaO2 from two cohorts from Valencia, Spain and Utah, USA. We compared SpO2 with measured SaO2 , compared the equations' accuracy in calculating PaO2 /FiO2 and determined how often patients would be misclassified at clinically important thresholds. We compared estimated PaO2 /FiO2 to measured PaO2 /FiO2 using the Spearman correlation. RESULTS: Pairwise correlation of SpO2 with SaO2 was moderate (rho = 0.66; P < 0.01). Both equations performed similarly among patients with lower PaO2 /FiO2 ratios. The Ellis equation estimated PaO2 /FiO2 from SpO2 more accurately than the Rice equation in patients with PaO2 /FiO2 ≥200. Simple agreement between calculated and measured P/F was 91% and 92%, respectively. CONCLUSIONS: The Ellis equation was more accurate than the Rice equation for estimating PaO2 /FiO2 , especially at higher levels of P/F ratio. Estimation of PaO2 /FiO2 from SpO2 is accurate enough for initial oxygenation assessment. Ellis and Rice equations could misclassify 20% and 30% of patients, respectively, at higher levels of PaO2 /FiO2 . For patients with abnormal oxygenation falling near thresholds for clinical decision making, arterial blood gas measurement preferably on room air is more accurate.

Does prolonged onset of symptoms have a prognostic significance in community-acquired pneumonia?

BACKGROUND AND OBJECTIVE: Severity assessment is made at the time of the initial clinical presentation in patients with community-acquired pneumonia (CAP). It is unclear how the gap between time of presentation and duration of symptoms onset may impact clinical outcomes. Here we evaluate the association of prolonged onset of symptoms (POS) and the impact on clinical outcomes among hospitalized patients with CAP. METHODS: This was a prospective, multicentre study of CAP in Spain. The primary outcomes were the clinical factors associated with POS defined as days from symptoms onset to pneumonia diagnosis >7 days. The secondary outcomes were intensive care unit (ICU) admission, the presence of suppurative complications, septic shock and 30-day mortality. RESULTS: We enrolled 1038 patients diagnosed of CAP: 152 (14.6%) patients had a POS. In multivariate analysis, the presence of prior corticosteroid therapy, alcohol abuse, prior antibiotic therapy, and confusion, urea, respiratory rate, blood pressure and age 65 years or older score 0-1 was independently associated with POS. Patients with POS had a higher incidence of suppurative complications, but not of 30-day mortality when compared with a shorter onset of symptoms. CONCLUSIONS: Approximately 15% of patients diagnosed with CAP had POS. Risk factors associated with POS were previous corticosteroids and antibiotic therapy, alcoholism and less severe pneumonia. POS was associated with a higher rate of suppurative complications and less need for ICU admission.

Hypoxemia adds to the CURB-65 pneumonia severity score in hospitalized patients with mild pneumonia.

BACKGROUND: Hypoxemia may influence the prognosis of patients with mild pneumonia, regardless of the initial CURB-65 score (confusion, blood urea nitrogen > 20 mg/dL, respiratory rate > 30 breaths/min, blood pressure < 90/60 mm Hg, and age ≥ 65 y). OBJECTIVE: To determine the risk factors associated with hypoxemia and the influence of hypoxemia on clinical outcomes in hospitalized patients with mild pneumonia. METHODS: We performed a multicenter prospective cohort study of 585 consecutive hospitalized patients with mild pneumonia (CURB-65 groups 0 and 1). We stratified the patients according to the presence of hypoxemia, defined as a P(aO(2))/F(IO(2)) < 300 mm Hg on admission. We assessed the risk factors associated with hypoxemia, hypoxemia's influence on the course of pneumonia, and clinical outcomes (mortality, hospital stay, and need for intensive care unit admission), with multivariable regression. RESULTS: Fifty percent of the patients (294 cases) had hypoxemia on admission. The risk factors independently associated with hypoxemia were: bilateral radiological involvement (odds ratio 2.8, 95% CI 1.1-7.5), history of COPD (odds ratio 2.5, 95% CI 1.4-4.3), and hypoalbuminemia (odds ratio 2.0, 95% CI 1.1-3.5). The hypoxemic patients had longer hospital stay, higher intensive care unit admission rate, higher rate of severe sepsis, and higher mortality than the non-hypoxemic patients. CONCLUSIONS: Hypoxemia in patients with mild pneumonia is independently associated with several adverse clinical and radiological variables, and the hypoxemic patients had worse clinical outcomes than the non-hypoxemic patients. Therefore, additional attention should be paid to the presence of hypoxemia, regardless of a low CURB-65 score.

Ventilación mecánica no invasiva en la Comunidad Valenciana: de la teoría a la práctica / Noninvasive Mechanical Ventilation in Valencia, Spain: From Theory to Practice

Objetivo: obtener datos representativos acerca del abordaje, la prevalencia y los recursos disponibles para la práctica de la ventilación mecánica no invasiva (VMNI), tanto en pacientes agudos como en domicilio.Métodomediante un cuestionario específico por vía electrónica reforzado con encuesta telefónica se recabó información de todos los hospitales de la Comunidad Valenciana(AU)

Resultados: se obtuvieron datos del 70% de los centros encuestados. Durante los episodios agudos la VMNI se realizaba en la unidad de cuidados intensivos en el 100% de los casos y en el servicio de neumología en el 88%; las enfermedades más frecuentes (media±desviación estándar) fueron las siguientes: enfermedad pulmonar obstructiva crónica (EPOC; 60±20%), síndrome de obesidad-hipoventilación (22±12%), enfermedades neuromusculares (6,5±8%), cifoescoliosis (6,5±7%) y otras (4±11%). La VMNI se realizaba en urgencias en el 69% de los casos, en medicina interna en el 37%, en la unidad de hospitalización domiciliaria en el 19% y en otros servicios en el 12%. Ninguno de los hospitales encuestados dispone de Unidad de Cuidados Intermedios y existió gran disparidad entre los sistemas de VMNI empleados. La VMNI en domicilio se efectuaba en el 88% de los hospitales y se aplicaba a pacientes con EPOC (31±18%), síndrome de obesidad-hipoventilación (30±18%), enfermedades neuromusculares (16±23%), cifoescoliosis (12±10%) y otras enfermedades (11±17%), con amplia variabilidad en el número de pacientes por hospital. El tipo de interfaz domiciliaria fue nasal en el 65±32% de los casos, oronasal en el 33±33%, traqueostomía en el 2±3% y bucal en el 1±3%. Sólo disponía de consulta monográfica el 31,3% de los hospitales. El control domiciliario lo realizaban principalmente empresas suministradoras. La prevalencia calculada de VMNI domiciliaria fue 29/100.000. Sólo el 50% de los centros disponía en neumología de protocolos de VMNI para pacientes hospitalizados un 44% para domicilio, un 19% para urgencias y un 12% para medicina interna(AU)

Conclusiones: se observan importantes carencias en recursos humanos y técnicos, disparidad en el material empleado y escasez en sistemas de apoyo. Aunque en la mayoría de los hospitales la VMNI se realiza en pacientes agudos, el número y el tipo de pacientes que reciben VMNI en su domicilio son más variables, pero la VMNI en domicilio presenta alta prevalencia. Además, se objetiva falta de protocolos escritos tanto para pacientes agudos como crónicos

Objective: To obtain representative data on the frequency of use and availability of resources for noninvasive mechanical ventilation (NIV) in hospitals (acute respiratory failure) and at home (chronic respiratory failure).MethodWe sent a purpose-designed questionnaire to all the hospitals in the Autonomous Community of Valencia, Spain and followed up with a telephone interview(AU)

Results: Seventy percent of the hospitals responded to the survey. NIV was used to treat patients with acute respiratory episodes in 100% of the intensive care units and in 88% of the respiratory medicine departments. The most common diseases were chronic obstructive pulmonary disease (COPD) (mean [SD] 60% [20%]), obesity hypoventilation syndrome (22% [12%]), neuromuscular diseases (6.5% [8%]), and kyphoscoliosis (6.5% [7%]). Other diseases accounted for 4% [11%] of cases. Emergency departments used NIV in 69% of patients, internal medicine departments in 37%, hospital-based home care units in 19%, and other departments in 12%. None of the hospitals that responded to the survey had an intermediate care unit and considerable differences were found in terms of NIV systems used. Home NIV was provided by 88% of hospitals. Patients using home NIV had COPD (31% [18%]), obesity hypoventilation syndrome (30% [18%]), neuromuscular diseases (16% [23%]), kyphoscoliosis (12% [10%]), and other diseases (11% [17%]). Patient numbers varied greatly from one hospital to the next. Home NIV was delivered using a nasal interface in 65% (32%) of cases, an oral-nasal interface in 33% (33%), a tracheostomy tube in 2% (3%), and a mouthpiece in 1% (32%). Only 31.3% of hospitals has a specialized home NIV unit. Home monitoring was performed mainly by service providers. We calculated that home NIV was used in 29 individuals per 100 000 population. Only 50% of the respiratory medicine departments surveyed had written hospitalization protocols; the corresponding percentages for other departments were 44% for home care units, 19% for emergency departments, and 12% for internal medicine departments.

Conclusions: We observed differences in the type of requirement used, and considerable deficiencies in the availability of human and material resources and support systems. Although NIV is mostly used in hospitals to treat patients with acute respiratory failure, home NIV is also very common and is characterized by greater variability in terms of the number and type of patients. We also observed deficiencies in terms of written protocols for patients with acute and chronic disease.

[Noninvasive mechanical ventilation in Valencia, Spain: from theory to practice]. / Ventilación mecánica no invasiva en la Comunidad Valenciana: de la teoría a la práctica.

OBJECTIVE: To obtain representative data on the frequency of use and availability of resources for noninvasive mechanical ventilation (NIV) in hospitals (acute respiratory failure) and at home (chronic respiratory failure). METHOD: We sent a purpose-designed questionnaire to all the hospitals in the Autonomous Community of Valencia, Spain and followed up with a telephone interview. RESULTS: Seventy percent of the hospitals responded to the survey. NIV was used to treat patients with acute respiratory episodes in 100% of the intensive care units and in 88% of the respiratory medicine departments. The most common diseases were chronic obstructive pulmonary disease (COPD) (mean [SD] 60% [20%]), obesity hypoventilation syndrome (22% [12%]), neuromuscular diseases (6.5% [8%]), and kyphoscoliosis (6.5% [7%]). Other diseases accounted for 4% [11%] of cases. Emergency departments used NIV in 69% of patients, internal medicine departments in 37%, hospital-based home care units in 19%, and other departments in 12%. None of the hospitals that responded to the survey had an intermediate care unit and considerable differences were found in terms of NIV systems used. Home NIV was provided by 88% of hospitals. Patients using home NIV had COPD (31% [18%]), obesity hypoventilation syndrome (30% [18%]), neuromuscular diseases (16% [23%]), kyphoscoliosis (12% [10%]), and other diseases (11% [17%]). Patient numbers varied greatly from one hospital to the next. Home NIV was delivered using a nasal interface in 65% (32%) of cases, an oral-nasal interface in 33% (33%), a tracheostomy tube in 2% (3%), and a mouthpiece in 1% (32%). Only 31.3% of hospitals has a specialized home NIV unit. Home monitoring was performed mainly by service providers. We calculated that home NIV was used in 29 individuals per 100 000 population. Only 50% of the respiratory medicine departments surveyed had written hospitalization protocols; the corresponding percentages for other departments were 44% for home care units, 19% for emergency departments, and 12% for internal medicine departments. CONCLUSIONS: We observed differences in the type of requirement used, and considerable deficiencies in the availability of human and material resources and support systems. Although NIV is mostly used in hospitals to treat patients with acute respiratory failure, home NIV is also very common and is characterized by greater variability in terms of the number and type of patients. We also observed deficiencies in terms of written protocols for patients with acute and chronic disease.