Immunomodulatory effects of pidotimod in adults with community-acquired pneumonia undergoing standard antibiotic therapy.

The morbidity and mortality of community-acquired pneumonia (CAP) are still elevated and two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response. Adjuvants, including corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects but their efficacy is only partial. We examined the immunomodulatory activity of Pidotimod (PDT), a synthetic dipeptide molecule in adult patients hospitalized for CAP. Sixteen patients with a diagnosis of CAP and a PSI score III or IV and/or a CURB-65 0-2 were randomized to receive either levofloxacin 500 mg b.i.d. alone or levofloxacin plus PDT (800mg, 2 daily doses). Blood samples were drawn at baseline (T0), before initiation of therapy, as well as 3 (T3), and 5 (T5) days after initiation of therapy. Immunologic and clinical parameters were analyzed at each time point. Supplementation of antibiotic therapy with PDT resulted in an upregulation of antimicrobial and of immunomodulatory proteins as well as in an increased percentage of Toll like receptor (TLR)2- and TLR4, and of CD80- and CD86-expressing immune cells. Notably, Pidotimod supplementation was also associated with a robust reduction of TNFα-producing immune cells. No significant differences were observed in clinical parameters. These results confirm that supplementation of antibiotic therapy with Pidotimod in patients with CAP results in a potentially beneficial modulation of innate immunity.

Osteopathic manipulative treatment as a useful adjunctive tool for pneumonia.

Pneumonia, the inflammatory state of lung tissue primarily due to microbial infection, claimed 52,306 lives in the United States in 2007 (1) and resulted in the hospitalization of 1.1 million patients (2). With an average length of in-patient hospital stay of five days (2), pneumonia and influenza comprise significant financial burden costing the United States $40.2 billion in 2005 (3). Under the current Infectious Disease Society of America/American Thoracic Society guidelines, standard-of-care recommendations include the rapid administration of an appropriate antibiotic regiment, fluid replacement, and ventilation (if necessary). Non-standard therapies include the use of corticosteroids and statins; however, these therapies lack conclusive supporting evidence (4). (Figure 1) Osteopathic Manipulative Treatment (OMT) is a cost-effective adjunctive treatment of pneumonia that has been shown to reduce patients' length of hospital stay, duration of intravenous antibiotics, and incidence of respiratory failure or death when compared to subjects who received conventional care alone (5). The use of manual manipulation techniques for pneumonia was first recorded as early as the Spanish influenza pandemic of 1918, when patients treated with standard medical care had an estimated mortality rate of 33%, compared to a 10% mortality rate in patients treated by osteopathic physicians (6). When applied to the management of pneumonia, manual manipulation techniques bolster lymphatic flow, respiratory function, and immunological defense by targeting anatomical structures involved in the these systems(7,8, 9, 10). The objective of this review video-article is three-fold: a) summarize the findings of randomized controlled studies on the efficacy of OMT in adult patients with diagnosed pneumonia, b) demonstrate established protocols utilized by osteopathic physicians treating pneumonia, c) elucidate the physiological mechanisms behind manual manipulation of the respiratory and lymphatic systems. Specifically, we will discuss and demonstrate four routine techniques that address autonomics, lymph drainage, and rib cage mobility: (1) Rib Raising, (2) Thoracic Pump, (3) Doming of the Thoracic Diaphragm, and (4) Muscle Energy for Rib 1.

Pathomorphosis of experimental infection in mice, infected by Streptococcus pneumoniae, under the effect of immunotropic drugs.

Pathomorphological changes in the organs of animals intranasally infected with Streptococcus pneumoniae were studied under conditions of immunotropic therapy added to antibiotic therapy. The pathomorphosis in the lungs, spleen, and thymus in animals treated with likopid, tinrostim, and roncoleukin was described. A positive time course of the pathological process in experimental animals in comparison with intact animals and animals receiving no immunotropic drugs was demonstrated.

[About non-specific prophylaxis of infections typical for organized groups].

Respiratory tract infections and pyodermia are typical for personnel doing military service under conscription. Risk of progression of these infections is connected with activation of carry-over of causative agents among military personnel during replacement and decrease in immunity of conscripts. Usage of medication "Karmolis Kapli" for the purpose of prophylaxis allows to reduce cases of respiratory tract infections among the military personnel. Among the military servicemen who had take "Karmolis Kapli" was noted reduction of community-acquired pneumonia, tonsillitis and pyodermia morbidity. Non-specific protective effect of medication "Karmolis Kapli" is conditioned by increase of the common resistance of the body. For the purpose of prophylaxis it is necessary to use this medication during the personnel formation before the beginning of seasonal morbidity.

Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case-control study.

OBJECTIVES: To examine whether use of opioids or benzodiazepines is associated with risk of community-acquired pneumonia in older adults. DESIGN: Population-based case-control study. SETTING: An integrated healthcare delivery system. PARTICIPANTS: Community-dwelling, immunocompetent adults aged 65 to 94 from 2000 to 2003. Presumptive pneumonia cases were identified from health plan automated data and validated through medical record review. Two controls were selected for each case with pneumonia, matched on age, sex, and calendar year. MEASUREMENTS: Information about opioid and benzodiazepine use came from computerized pharmacy data. Information on covariates including comorbid illnesses and functional and cognitive status came from medical record review and electronic health data. RESULTS: One thousand thirty-nine validated cases of pneumonia and 2,022 matched controls were identified. One hundred forty-four (13.9%) cases and 161 (8.0%) controls used prescription opioids (adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76 vs nonuse). Risk was highest for opioids categorized as immunosuppressive based on immunological studies (OR = 1.88, 95% CI = 1.26-1.79 vs nonuse), whereas for nonimmunosuppressive opioids the OR was 1.23 (95% CI = 0.89-1.69). Risk was highest in the first 14 days of use (OR = 3.24, 95% CI = 1.64-6.39 vs nonuse). For long-acting opioids, the OR was 3.43 (95% CI = 1.44-8.21) versus nonuse, whereas for short-acting opioids, it was 1.27 (95% CI = 0.98-1.64). No greater risk was seen for current benzodiazepine use compared to nonuse (OR = 1.08, 95% CI = 0.80-1.47). CONCLUSION: Use of opioids but not benzodiazepines was associated with pneumonia risk. The differences in risk seen for different opioid regimens warrant further study.

[Cytokine changes in community-acquired pneumonia in elderly and intervention of traditional Chinese medicine].

OBJECTIVE: To make a study of the cytokine changes in community-acquired pneumonia (CAP) in the elderly and the intervention of traditional Chinese medicine that can clear away the lung-heat and dissipate blood stasis (Qingfeihuayu soup). METHOD: The 82 cases with CAP in the elderly were divided at random into two treatment group and control group. Based on heteropathy, the treatment group was given Qingfeihuayu soup two times a day. The control group was given Rocephin 2 g once daily for 7 days. The clinical effect and the changes in TNF-alpha, IL-6 and IL-10 were observed before and after the treatment. A healthy group was also set up. RESULT: Before treatment, IL-6 and TNF-alpha in both groups were higher than the healthy group (P < 0.01) and IL-10 lower than the healthy group (P < 0.01). After treatment, IL-6 and TNF-alpha in both groups decreased (P < 0.01) while IL-10 in treatment group increased. There existed a great difference compared with the control group (P < 0.01). The total effective rate in the treatment group is 92.50% while the control group is 85.71%. thus have a great difference (P < 0.05). CONCLUSION: During the process of the development of CAP in the elderly, there existed the phenomenon of the excessive release of TNF-alpha, IL-6 and the too much inhibition of IL-10. The unbalance of TNF-alpha, IL-6, IL-10 can be a monitoring index reflecting the severity of the disease. The Chinese medicine Qingfeihuayu soup has obviously have regulating and clinical effect.

Statin use and risk of community acquired pneumonia in older people: population based case-control study.

OBJECTIVE: To test the hypothesis that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of community acquired pneumonia. DESIGN: Population based case-control study. SETTING: Group Health, a large integrated healthcare delivery system. Population Immunocompetent, community dwelling Group Health members aged 65 to 94; two matched controls for each case with pneumonia. Information on comorbid illnesses and functional and cognitive status, potential confounders of the association between statin use and risk of pneumonia, came from medical record review and computerised pharmacy data. MAIN OUTCOME MEASURE: Adjusted estimates of risk of pneumonia in relation to current statin use. RESULTS: 1125 validated cases of pneumonia and 2235 matched controls were identified. Compared with controls, cases were more likely to have chronic lung and heart disease, especially severe disease, and functional or cognitive impairment. Current statin use was present in 16.1% (181/1125) of cases and 14.6% (327/2235) of controls (adjusted odds ratio 1.26, 95% confidence interval 1.01 to 1.56). Among cases admitted to hospital and matched controls, current statin use was present in 17.2% (68/395) of cases and 14.2% (112/788) of controls (adjusted odds ratio 1.61, 1.08 to 2.39, compared with non-use). In people in whom statins were indicated for secondary prevention, the adjusted odds ratio for risk of pneumonia in relation to current statin use was 1.25 (0.94 to 1.67); in those with no such indication, it was 0.81 (0.46 to 1.42). CONCLUSIONS: Statin use was not associated with decreased risk of pneumonia among immunocompetent, community dwelling older people. Findings of previous studies may reflect "healthy user" bias.

Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers.

BACKGROUND: Vitamin E and beta-carotene affect various measures of immune function and accordingly might influence the predisposition of humans to infections. However, only few controlled trials have tested this hypothesis. STUDY OBJECTIVE: To examine whether vitamin E or beta-carotene supplementation affects the risk of pneumonia in a controlled trial. DESIGN AND SETTING: The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study, a randomized, double-blind, placebo-controlled trial that examined the effects of vitamin E, 50 mg/d, and beta-carotene, 20 mg/d, on lung cancer using a 2 x 2 factorial design. The trial was conducted in the general community in southwestern Finland in 1985 to 1993; the intervention lasted for 6.1 years (median). The hypothesis being tested in the present study was formulated after the trial was closed. PARTICIPANTS: ATBC study cohort of 29,133 men aged 50 to 69 years, who smoked at least five cigarettes per day, at baseline. MAIN OUTCOME MEASURE: The first occurrence of hospital-treated pneumonia was retrieved from the national hospital discharge register (898 cases). RESULTS: Vitamin E supplementation had no overall effect on the incidence of pneumonia (relative risk [RR], 1.00; 95% confidence interval [CI], 0.88 to 1.14) nor had beta-carotene supplementation (RR, 0.98; 95% CI, 0.85 to 1.11). Nevertheless, the age of smoking initiation was a highly significant modifying factor. Among subjects who had initiated smoking at a later age (> or =21 years; n = 7,469 with 196 pneumonia cases), vitamin E supplementation decreased the risk of pneumonia (RR, 0.65; 95% CI, 0.49 to 0.86), whereas beta-carotene supplementation increased the risk (RR, 1.42; 95% CI, 1.07 to 1.89). CONCLUSIONS: Data from this large controlled trial suggest that vitamin E and beta-carotene supplementation have no overall effect on the risk of hospital-treated pneumonia in older male smokers, but our subgroup finding that vitamin E seemed to benefit subjects who initiated smoking at a later age warrants further investigation.

Evolución clínica y pronóstico del paciente hospitalizado por neumonía adquirida en la comunidad según lugar de admisión / Clinical evolution and prognosis of the hospitalized patient by community-acquired pneumonia according to admission place

La evaluación de la gravedad del paciente con neumonía comunitaria (NAC) permite decidir el lugar de manejo, la extensión del estudio microbiológico y elección del tratamiento antimicrobiano. Objetivos: Describir la evolución clínica y pronóstico del adulto inmunocompetente hospitalizado por neumonía comunitaria según lugar de admisión. Resultados: Durante el período 1999-2001, se evaluaron 463 adultos con NAC en el servicio de urgencia de un hospital docente, 55 por ciento eran varones, 76 por ciento tenía comorbilidad, un tercio había recibido antibióticos antes del ingreso y 75 por ciento correspondían a las categorías de riesgo elevado de Fine (Clases III-V). De acuerdo a su gravedad, cerca del 40 por ciento de los pacientes fueron admitidos a la Unidad de Cuidados Intermedios (UTIM)o UCI. La etiología fue establecida en 25 por ciento de los casos, especialmente en aquellos internados en unidades especializadas. Los patógenos más frecuentes aislados fueron Streptococcus pneumoniae (10,2 por ciento), Haemophilus influenzae (3,7 por ciento), Staphylococcus aureus (2,8 por ciento) y bacilos Gram negativos entéricos (5,2 por ciento). En la admisión al hospital, la edad avanzada, presencia de comorbilidad, disnea, taquipnea, confusión mental, hipotensión, hipoxemia, acidosis metabólica, nitrógeno ureico elevado, hiperglicemia y compromiso radiográfico multilobar fueron más prevalentes en los pacientes admitidos a las unidades especializadas. La neumonía bacterémica, la infección por bacilos gram negativos entéricos y S aureus y la estadía prolongada en el hospital fueron más frecuentes en los pacientes admitidos a UTIM y UCI. El riesgo de complicaciones en el hospital y la letalidad en el hospital y seguimiento a 30 días también fueron más frecuentes en los pacientes admitidos a las unidades especializadas. Conclusión: El cuadro clínico, la evolución, riesgo de complicaciones y la letalidad del adulto inmunocompetente hospitalizado por neumonía comunitaria varía según el lugar de admisión al hospital.