Serum 25-hydroxyvitamin D levels in patients with Granulomatosis with Polyangiitis: association with respiratory infection

OBJECTIVES: To determine the possible association of serum 25-hydroxyvitamin D (25OHD) levels with disease activity and respiratory infection in granulomatosis with polyangiitis patients during two different periods: winter/spring and summer/autumn. METHODS: Thirty-two granulomatosis with polyangiitis patients were evaluated in the winter/spring, and the same patients (except 5) were evaluated in summer/autumn (n=27). The 25OHD levels were measured by radioimmunoassay. Disease activity was assessed by the Birmingham Vasculitis Activity Score Modified for Wegener's Granulomatosis (BVAS/WG) and antineutrophil cytoplasmic antibody (ANCA) positivity. Respiratory infection was defined according the Centers for Disease Control and Prevention criteria. RESULTS: 25OHD levels were lower among patients in winter/spring than in summer/autumn (32.31±13.10 vs. 38.98±10.97 ng/mL, p=0.04). Seven patients met the criteria for respiratory infection: 5 in winter/spring and 2 in summer/autumn. Patients with respiratory infection presented lower 25OHD levels than those without infection (25.15±11.70 vs. 36.73±12.08 ng/mL, p=0.02). A higher frequency of low vitamin D levels (25OHD<20 ng/mL) was observed in patients with respiratory infection (37.5% vs. 7.8, p=0.04). Serum 25OHD levels were comparable between patients with (BVAS/WG≥1 plus positive ANCA) and without disease activity (BVAS/WG=0 plus negative ANCA) (35.40±11.48 vs. 35.34±13.13 ng/mL, p=0.98). CONCLUSIONS: Lower 25OHD levels were associated with respiratory infection but not disease activity in granulomatosis with polyangiitis patients. Our data suggest that hypovitaminosis D could be an important risk factor for respiratory infection in granulomatosis with polyangiitis patients.

Valor prognóstico da procalcitonina em pacientes com infecções do trato respiratório inferior no ambiente hospitalar / Prognostic value of procalcitonin in hospitalized patients with lower respiratory tract infections

RESUMO Infecções do trato respiratório inferior são condições frequentes e potencialmente letais, consistindo nas principais causas de prescrição inadequada de antibióticos. A caracterização de sua gravidade e a predição prognóstica dos pacientes acometidos auxiliam na condução, permitindo maior acerto nas decisões sobre a necessidade e o local de internação, assim como a duração do tratamento. A incorporação de biomarcadores às estratégias classicamente utilizadas representa estratégia promissora, com destaque para a procalcitonina. O objetivo deste artigo foi apresentar uma revisão narrativa sobre a potencial utilidade e as limitações do uso da procalcitonina como um marcador prognóstico em pacientes hospitalizados portadores de infecções do trato respiratório inferior. Os estudos publicados sobre o tema são heterogêneos, no que tange à variedade de técnicas de mensuração da procalcitonina, seus valores de corte, os contextos clínicos e a gravidade dos pacientes incluídos. Os dados obtidos indicam valor moderado da procalcitonina para predizer o prognóstico de pacientes com infecções do trato respiratório inferior, não superior a metodologias classicamente utilizadas, e com utilidade que se faz notar apenas quando interpretados junto a outros dados clínicos e laboratoriais. De modo geral, o comportamento da procalcitonina, ao longo dos primeiros dias de tratamento, fornece mais informações prognósticas do que sua mensuração em um momento isolado, mas faltam informações sobre a custo-efetividade dessa medida em pacientes em terapia intensiva. Estudos que avaliaram o papel prognóstico da procalcitonina inicial em pacientes com pneumonia adquirida na comunidade apresentam resultados mais consistentes e com maior potencial de aplicabilidade prática, mas com utilidade limitada a valores negativos para a seleção de pacientes com baixo risco de evolução desfavorável.

ABSTRACT Lower respiratory tract infections are common and potentially lethal conditions and are a major cause of inadequate antibiotic prescriptions. Characterization of disease severity and prognostic prediction in affected patients can aid disease management and can increase accuracy in determining the need for and place of hospitalization. The inclusion of biomarkers, particularly procalcitonin, in the decision taken process is a promising strategy. This study aims to present a narrative review of the potential applications and limitations of procalcitonin as a prognostic marker in hospitalized patients with lower respiratory tract infections. The studies on this topic are heterogeneous with respect to procalcitonin measurement techniques, cutoff values, clinical settings, and disease severity. The results show that procalcitonin delivers moderate performance for prognostic prediction in patients with lower respiratory tract infections; its predictive performance was not higher than that of classical methods, and knowledge of procalcitonin levels is most useful when interpreted together with other clinical and laboratory results. Overall, repeated measurement of the procalcitonin levels during the first days of treatment provides more prognostic information than a single measurement; however, information on the cost-effectiveness of this procedure in intensive care patients is lacking. The results of studies that evaluated the prognostic value of initial procalcitonin levels in patients with community-acquired pneumonia are more consistent and have greater potential for practical application; in this case, low procalcitonin levels identify those patients with a low risk of adverse outcomes.

Evaluation of direct immunofluorescence test for diagnosis of upper respiratory tract infection by Chlamydia pneumoniae.

BACKGROUND: Chlamydia pneumoniae causes a variety of respiratory infections and is involved in cardiovascular diseases. Diagnosis of C. pneumoniae infection currently relies on antibody detection by microimmunofluorescence (MIF), which has limited use, and is the retrospective diagnosis for acute infection. OBJECTIVE: Find an effective early diagnosis of acute upper respiratory infection, or use in combination with MIF to accurately diagnose the infection by C. pneumoniae. MATERIAL AND METHOD: Direct immunofluorescence (DIF) was developed to detect C. pneumoniae in nasopharyngeal specimens obtained from patients with upper respiratory tract infection, and normal individuals. IgM and IgG antibodies against C. pneumoniae by MIF were determined for evaluation of the detected C. pneumoniae and seroconversion. RESULTS: DIF gave positive results in 29 of 37 (78.4%) samples from 31 patients. Fifteen samples positive by DIF illustrated antibody titers interpreted as acute C. pneumoniae infection, and eight DIF positive samples showed antibody titers of chronic infection. Negative results by both DIF and MIF were found in two patients and 23 of 25 by DIF but 20 of 25 by MIF in normal subjects. Five paired sera subsequently collected from three of the 31 patients illustrated seroconversion 2-4 months after the primary specimen collection, which gave positive results by DIF but negative for antibodies. Significant association was found between C. pneumoniae detection by DIF and antibodies by MIF when analysis was done in the group of patients and normal subjects (p < 0.001; Pearson chi-square test). CONCLUSION: DIF could be an alternative assay for early diagnosis of C. pneumoniae infection, and may be used in combination with MIF for accurate diagnosis of acute C. pneumoniae infection.

Hemoglobin level as a risk factor for lower respiratory tract infections.

OBJECTIVE: This prospective study was conducted to evaluate the role of hemoglobin level, as a risk factor for Lower Respiratory Tract Infections in children (LRTI). METHODS: 100 children who came to the outpatient department for LRTI were included in the study. Age and sex-matched 100 children, not having any respiratory illness, were taken as control. They were subjected to complete blood count (CBC),C-reactive protein estimation (CRP), Mantoux test and X-ray chest. Peripheral smear, serum ferritin and serum iron binding capacity were done for all anemic children. Results. Radiological evidence of pneumonia was present in 63 children(63%).Hyper inflated lungs were seen in 27 (27%). Mantoux was positive in 22 children (22%) of study group and none among control group. CRP > 6 mg/L was noted in 45 children (45%) of study group and 14 (14%) of control group. Seventy four of study group (74 %) and 33 of control group (33%) had anemia. Of the anemic children, 60 (60%) had iron deficiency,10 (10%) chronic inflammation and 4 (4%) had hemolytic anemia. These values were 30 (30%), 2 (2%) and 1 (1%)respectively for control group. Low hemoglobin level due to whatever etiology, was a risk factor (p=0.000). CONCLUSION: Anemic children were 5.75 times more susceptible to LRTI compared to the control group. Prevention of anemia, due to whatever etiology, will reduce the incidence of LRTI.

Evaluation of target concentration intervention strategy of gentamicin therapy in a malnourished patient population of south India.

BACKGROUND & OBJECTIVE: Aminoglycoside antibiotics, especially gentamicin, are widely used in suspected Gram-negative infections in India. Therapeutic drug monitoring is not commonly used for this drug in our population. We evaluated the target concentration intervention (TCI) strategy of gentamicin therapy in a predominantly malnourished patient population with lower respiratory tract infection in south India. METHODS: Patients who were prescribed gentamicin for suspected lower respiratory tract infection were randomized to any of the three groups, viz., control (CG), once daily dosing (ODD), and pharmacokinetic dosing (TCI) groups. Diagnosis was initially done by clinical evaluation and confirmed radiologically. Patients in CG received 80 mg gentamycin twice daily, ODD group received 160 mg once daily, and TCI groups received 160 mg once daily initially followed by dose revision based on serum drug levels. Blood samples were collected at peak and trough levels and assayed for gentamicin concentration. Dose adjustment was done in TCI group whereas the other groups received standard doses. Efficacy and safety were evaluated as outcome measures. RESULTS: Of the 52 patients included initially in the study, 43 (CG 20, ODD 12, TCI 11) completed the study. The doses administered to the study subjects were less than those prescribed in standard textbooks and guidelines. Patients in TCI group had their gentamicin doses revised upwardly to a dose of 4.3+/-0.6 mg/kg to achieve a peak gentamicin concentration of 12 to 15 microg/ml. Both ODD and TCI groups showed significant improvements in outcomes studied over the control group. INTERPRETATION & CONCLUSION: The results of our study indicated that once daily dosing of gentamycin was superior to multiple daily dosing in treating the lower respiratory tract infection in the study population. All patients in the ODD and TCI groups achieved satisfactory serum drug concentrations at administered doses (160 mg/day for ODD and <or= 200 mg/day for TCI group). In our study, target concentration intervention did not significantly improve the therapy outcomes. Since the study sample is small further research may be needed.

Etiology of acute lower respiratory tract infection.

OBJECTIVE: To identify pathogens responsible for acute severe lower respiratory tract infection (ALRTI) in under five children by non-invasive methods. METHOD: 95 children hospitalized with acute severe lower respiratory tract infection were investigated for identification of viruses, bacteria, chlamydia or mycoplasma by nasopharyngeal aspirates, blood culture and serology. RESULT: Etiological agents could be identified in 94% of the patients. Viruses from NP aspirate could be isolated in 36 (38%), bacterial isolates from blood cultures in 15 (16%); mycoplasma was identified in 23 (24%) and chlamydia in 10 (11%) by serological tests; mixed infections were present in 8 (8%) patients. CONCLUSION: Noninvasive methods can be useful in identifying etiological agents in severe ALRTI.

Trombocitosis en la edad pediátrica / Thrombocytosis in paedriatric patients

El valor normal de plaquetas varía entre 150,000 y 450,000 x mm al cubo. Se define trombocitosis como un recuento mayor de 600,000. Pueden ser primarias, por un trastorno mieloproliferativo o secundarias a un gran número de patologías. Objetivos: conocer en nuestro medio la frecuencia de ambos tipos de trombocitosis, describir las patologías asociadas y relacionar la magnitud de la trombocitosis con los diferentes diagnósticos. Material y métodos: se analizaron 18,000 hemogramas realizados entre enero y diciembre de 1998, en el Hospital Roberto del Río. Se evaluó sexo, recuento de plaquetas y leucocitos, hematocrito, hemoglobina, VCM, CHCM y diagnósticos. Resultados: se encontró trombocitosis en 584 exámenes (3,24 por ciento). Se evaluaron 334 fichas, el 62 por ciento eran de sexo masculino. El 0,9 por ciento presentó cifras de plaquetas > 1,000,000 x mm al cubo (dos casos fueron trombocitosis primarias: trombocitemia esencial y leucemia mieloide crónica y un caso de meningitis bacteriana). Las trombocitosis secundarias se asociaron a: infecciones (48,8 por ciento), principalmente respiratorias, deficiencia de hierro (18,6 por ciento) y daño tisular (12,6 por ciento). Conclusiones: la frecuencia de trombocitosis en niños es baja. Cuando la trombocitosis es menor de 1,000,000 x mm al cubo debe sospecharse una etiología secundaria

In vitro effect of complete Staphylococcus aureus extract on chemotaxis of polymorphonuclear cells in children with bronchial asthma and chronic relapsing upper airways infections

Se midieron la quimiocinesis y quimiotaxis en células polimorfonucleares (PMN) obtenidas de 51 niños de 1 a 8 años de edad, de uno y otro sexo. Grupo de casos: 41 niños con asma no alérgica e infecciones crónicas recurrentes de las vías aéreas superiores; los criterios diagnósticos fueron antecedentes de sibilancias relacionadas con un episodio de infección de las vías aéreas superiores y pruebas cutáneas negativas. Grupo testigo: 10 niños sanos. Se obtuvo una muestra de 10 ml de sangre venosa periférica. Los PMN se incubaron con solución de Hank para medir la quimiocinesis y con C5a y extracto de Staphylococcus aureus para medir quimiotaxis. Los valores de quimiocinesis en los niños sanos testigos y en los pacientes con asma bronquial no alérgica fueron de 46.0 ñ 7.1 vs 23.8 ñ 6.1 µm (p < 0.01). Los valores de quimiotaxis estimulada con C5a en los niños sanos testigos y en los pacientes con asma bronquial no alérgica fueron de 91.0 ñ 21.3 vs 92.3 ñ 21.0 µm (ns), y los valores de quimiotaxis estimulada con extracto de Staphylococcus aureus fueron de 97.0 ñ 22.4 vs 92.0 ñ 23.0 µm (ns). Estos resultados sugieren que los PMN de niños con asma no atópica tienen quimiocinesis reducida. Después de un estímulo quimiotáctico con C5a y extracto bacteriano, la movilidad de los leucocitos se corige y alcanza valores similares a los coexistentes en niños sanos

Use of serum bactericidal activity in assessing previous antibiotic therapy in acute lower respiratory tract infection in children.

Bactericidal activity in sera of children with acute lower respiratory tract infection was assayed to determine its effect on the outcome of blood culture. Parental reporting of prior antibiotic therapy was also determined. 14.4% of samples without serum bactericidal activity yielded pathogens from blood culture, whereas only 2.4% of samples with serum bactericidal activity yielded pathogens. A statistically significant correlation was found between isolation of pathogens by blood culture and serum bactericidal activity. Parental reporting could not be relied upon as there was no positive correlation.

Upper airway carriage by Haemophilus influenzae and Streptococcus pneumoniae in Australian aboriginal children hospitalised with acute lower respiratory infection.

When nasopharyngeal secretions from 171 Australian Aboriginal children hospitalized with acute lower respiratory tract infections (ALRI) were cultured selectively for Streptococcus pneumoniae and Haemophilus influenzae, 136 (79.5%) and 151 (88.3%) children yielded 166 and 254 isolates of S. pneumoniae and H. influenzae, respectively. In colonized subjects multiple populations of S. pneumoniae (20% of carriage-positive patients) and H. influenzae (55%) were common. Pneumococci belonging to 27 types or groups were identified. H. influenzae serotype b colonized 16.4% of all children studied. More than one half of 152 children tested were excreting antibiotics at the time of admission to hospital. Significantly fewer children with serum antibiotic residues were colonized with S. pneumoniae than were antibiotic free children. Antibiotic usage had no measurable impact on the isolation rate of H. influenzae.

Respuesta a la combinación de ambroxol-amoxicilina vs amoxicilina sola en pacientes con infecciones respiratorias agudas: estudio comparativo de los niveles de antibiótico en moco bronquial y sangre / Ambroxol-amoxiciline fixed combination vs amoxiciline in acute infectious respiratory conditions. Comparative study of antibiotic levels in bronchial mucus and blood

Se comparó en un estudio al azar y en forma ciega la respuesta a la combinación de ambroxol-amoxicilina (tratamiento A) vs amoxicilina sola (tratamiento B) por vía oral en un grupo de 40 pacientes adultos, que cursaban con infecciones bacterianas del tracto respiratorio bajo. Se incluyeron sujetos de 20 a 55 años de edad, masculinos y femeninos con medias de 40.5 años para el grupo A y de 34.5 para el grupo B. Se consideró como índice de mejoría temprana la desaparición de la fiebre y como curación la desaparición de los signos clínicos o paraclínicos en el enfermo. Se cultivó la expectoración en todos los casos y se realizó antibiograma. La concentración del antibiótico en sangre y moco se determinaron por medio de bioensayo con cultivos de Sarcina lútea en todos los pacientes. Se compararon los dos grupos de tratamiento para la desaparición de síntomas, mejoría de la infección y diferencias en la concentración del antibiótico en la sangre y moco. Se analizaron las diferencias por la prueba de Wilcoxon para muestras pareadas y ANOVA unidireccional (prueba de Kruskall-Wallis). Finalmente se identificaron las variables asociadas a la mejoría temprana por un modelo de regresión lineal múltiple por pasos y un modelo de regresión logística múltiple. Al compararse con la prueba de Wilcoxon se encontraron diferencias significativas a favor de la combinación de ambroxol y amoxicilina para las concentraciones del antibiótico en sangre y moco (p=0.00021), y para la desaparición de la fiebre (p=0.00036), esto fue confirmado por las pruebas de ANOVA. Por este método se encontró una diferencia marginal en las cifras de leucocitos al inicio a favor de los pacientes del grupo A (p=0.02). Al aplicarse el modelo de regresión lineal, la única variable que se ajustó adecuadamente, fueron las concentraciones del antibiótico en el moco. Con esto podemos concluir que en los pacientes tratados con la combinación de ambroxol-amoxicilina, los niveles del antibiótico en sangre y moco son más altos y su mejoría clínica es significativamente más temprana. Esta mejoría parece estar dada por las altas concentraciones del antibiótico en el moco de la expectoración, por lo que el efecto sinérgico del ambroxol en la amoxicilina, establece una diferencia notable que haría deseable el uso de la combinación en pacientes seleccionados con infecciones respiratorias bacterianas.

Importancia de la asociación ambroxol-amoxicilina en el tratamiento de la infección bacteriana del aparato respiratorio bajo en el niño mexicano / Importance of the ambroxol-amoxiciline asociation in the treatment of the bacterial respiratory infection in Mexican children

Existen publicados en la literatura internacional, diversos estudios cuidadosamente elaborados, que han valorado la influencia decisiva del nuevo mucolítico clorhidrato de trans-4-[(2-amino-3-5-dibromobencil)amino]-ciclohexanol (ambroxol) sobre la actividad del P-hidroxiderivado de la alfa-aminobecil penicilina (amoxacilina) cuando se administran asociados. Esta asociación produce un marcado efecto sinérgico, aumentando significativamente los niveles del antibiótico en los líquidos broncopulmonares, así como incrementando su penetración en el tejido pulmonar. Los reportes de Spátula1, Wiemeyer2 y Gené3 apoyan este sinergismo. En base a esto se diseñó un estudio para valorar la eficacia de la combinación en el tratamiento de las infecciones de vías respiratorias bajas en niños y la distribución del antibiótico en suero y moco broncopulmonar utilizando un método de lavado bronquial simplificado. Se estudiaron 20 menores que ingresaron consecutivamente al servicio de medicina del Hospital Infantil Aragón, siendo el 45 porciento varones y 55 porciento mujeres. Sus edades variaron de cuatro a once años. Todos presentaron un episodio infeccioso agudo de vías respiratorias siendo el 60 porciento bronquitis, 20 porciento neumonía, 10 porciento absceso pulmonar, y 10 porciento bronquiectasias infectadas. Se les ingresó al azar en dos grupos de tratamiento después de habérseles realizado historia clínica y evaluación de laboratorio y gabinete completas. A todos se les practicó lavado bronquial con frotis y cultivo de expectoración y se les inició tratamiento intrahospitalario con amoxicilina sola o la combinación de ambroxol-amoxicilina, a dosis de 50 mg del antibiótico por kg de peso/día divididos en tres dosis cada ocho horas durante 10 días. Se encontró una diferencia ampliamente significativa en las concentraciones del antibiótico en suero y moco de los pacientes que recibieron la combinación (p < 0.0001) aunque no podemos explicar el mecanismo involucrado en los niveles séricos.

Detección viral en infecciones respiratorias agudas en niños hospitalizados: estudio serológico / Viral detection in acute respiratory infections in hospitalized children: serologic study

Se determinó la participación viral en las IRA del lactante desde 1980 a 1982 utilizando técnicas serológicas. Se confirmó una positividad viral en el 58.4% de los casos, siendo los principales virus detectados: el respiratorio sincicial (VRS) y los virus parainfluenza (PI). En un 14,5% de las infecciones respiratorias agudas (IRA) estudiadas se confirmaron dos o más virus. El VRS predominó en los menores de 6 meses, en cambio los virus PI en los mayores de esa edad y los adenovirus (AD) en los mayores de 1 año. El VRS y los virus PI fueron importantes en bronquitis obstructivas agudas y recidivantes, neumonitis y cuadros mixtos. El VRS predominó en bronconeumonias. No hubo mayores diferencias desde el punto de vista clínico, de laboratorio y radiológico entre los niños con resultados positivos o negativos. Se destaca la importancia de la serología como método de detección viral en aquellos lugares en que no se puede efectuar un estudio mas completo