Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children.
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The role of repeated infections early in life in the development of childhood asthma and allergies has not been clarified. The aim of this study was to investigate the effect of repeated episodes of fever and antibiotic treatments during the first years of life on the prevalence of asthma, bronchial hyperresponsiveness (BHR), and atopy at school age in a representative population. Random samples of schoolchildren aged 5-7 yrs (n=7,545) and 9-11 yrs (n=7,498) were studied using the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol. To assess the prevalence of disease and early childhood exposures, parental questionnaires were administered (response rates 82.2% and 85.3%, respectively). In addition, children underwent skin prick tests, hypertonic saline challenge and blood sampling for the measurement of serum immunoglobulin (Ig)E. Repeated episodes of fever and antibiotic treatment in early life were strongly associated with the prevalence of asthma (odds ratio (OR)=7.95; 95% confidence interval (CI) 6.02-10.50) and current wheeze at school age. Within asthmatic children the number of fever episodes and antibiotic courses were strongly inversely related to the prevalence of atopy (OR=0.25; 95% CI 0.11-0.54 for skin test reactivity) and BHR (OR=0.31; 95% CI 0.10-0.92). Furthermore, asthmatic children with recurrent early childhood infections were at a lower risk of being symptomatic at school age. When considering atopic and nonatopic asthmatic children separately, the highest risk of asthma with repeated early childhood infections was found for nonatopic asthma (OR=24.29; 95% Cl 11.86-49.76). These findings suggest that a subgroup of children with a triggering or inducing of asthmatic symptoms through repeated early childhood infections exists within the "asthma syndrome" which has a better prognosis and is less related to the atopic phenotype. (+info)
Pharmacokinetics and pharmacodynamics of fluoroquinolones in the respiratory tract.
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Pharmacokinetic and pharmacodynamic features are important predictors of the therapeutic efficacy of an antibiotic. In respiratory tract infection, study of the clinical implication of pharmacodynamic features is complicated as infection occurs at several distinct sites. To ensure microbiological efficacy, antibiotics should not only be active against common respiratory pathogens but should also penetrate to the sites of infection. The newer fluoroquinolones combine good activity against Gram-negative and "atypical" organisms with extended Gram-positive activity, and are unaffected by penicillin susceptibility status and beta-lactamase production. Long terminal half-lives allow once-or twice-daily dosing, and a concentration in lung tissue at levels many times higher than is observed in the serum. Although the benefit of antibiotics in some lower respiratory tract infections has been questioned, they have proved effective in community-acquired pneumonia and acute exacerbations of chronic obstructive pulmonary disease. Early studies of oral fluoroquinolones versus intravenous or oral treatment with one or more agents in community-acquired pneumonia have shown promise. Although resistance is a potential problem with increased fluoroquinolone use, its rapid development is not anticipated. In conclusion, the broad-spectrum antimicrobial activity, tissue distribution and safety profile of fluoroquinolones suggest that they have a place in respiratory tract infection. (+info)
Upper respiratory tract infection, heterologous immunisation and meningococcal disease.
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To test the hypothesis that an episode of upper respiratory tract infection or heterologous immunisation is a predisposing factor for the occurrence of meningococcal disease, data from 377 cases of meningococcal disease and their household contacts (n = 1124) were analysed by conditional logistic regression analysis with stratification for household. The odds ratio for a recent upper respiratory tract infection for patients versus household contacts, adjusted for age and the presence of an underlying predisposing disease, was 2.8 and that for recent heterologous immunisation 1.0. These results support previous observations regarding the association between a preceding upper respiratory tract infection and the occurrence of meningococcal disease; however, no association was found between preceding heterologous immunisation and meningococcal disease. Therefore, increased alertness after heterologous immunisation does not seem warranted. (+info)
Effect of fluticasone propionate and salmeterol on Pseudomonas aeruginosa infection of the respiratory mucosa in vitro.
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The purpose of this study was to investigate the effect of the corticosteroid, fluticasone propionate (FP), on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model in vitro. Organ cultures infected with P. aeruginosa had significantly (p< or =0.05) elevated levels of mucosal damage and significantly (p< or =0.05) less ciliated cells compared to controls. Preincubation of tissue with FP (10(-6) or 10(-5) but not 10(-7) M) prior to P. aeruginosa infection significantly (p< or =0.05) reduced the bacterially induced mucosal damage in a concentration-dependent manner. FP (10(-5) M) also significantly (p< or =0.05) prevented loss of ciliated cells. FP did not alter the density of bacteria adherent to the different mucosal features of the organ cultures, but did reduce total bacterial numbers due to the reduced amount of damaged tissue, which is a preferred site of P. aeruginosa adherence. It has previously been shown that the long-acting beta2-agonist salmeterol (4 x 10(-7)M) also reduces the mucosal damage caused by P. aeruginosa infection, probably via elevation of intracellular cyclic adenosine monophosphate concentrations. Preincubation of tissue with both 10(-7)M FP and 10(-7)M salmeterol, concentrations at which they did not by themselves influence the effect of P. aeruginosa infection, significantly (p< or =0.05) reduced P. aeruginosa-induced loss of cilia. However, there was no additional benefit from adding 4 x 10(-7)M salmeterol to 10(-6)M FP. In conclusion fluticasone propionate reduced mucosal damage caused by P. aeruginosa infection in vitro and preserved ciliated cells. There was a synergistic action with salmeterol in the preservation of ciliated cells. (+info)
Guillain-Barre syndrome: rehabilitation outcome and recent developments.
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Guillain-Barre syndrome is the most common polyneuropathy causing major disability and respiratory failure. Respiratory complications are the main cause of death. Improved respiratory care and new treatment strategies such as plasmaphoresis and immunoglobulin have been shown to improve outcome. We studied the course and outcome of 37 patients with Guillain-Barre syndrome who were admitted to a rehabilitation and respiratory care facility over a 10-year period. There were 21 males and 16 females with a mean age of 62+/-3 years. Fourteen patients developed respiratory failure requiring endotracheal intubation and mechanical ventilation. The mean duration of mechanical ventilation was 38+/-10 days. All patients were successfully liberated from the ventilator. However, 83 percent of the patients were moderately to severely disabled at the time of discharge. Thirteen out of 37 (35 percent) developed long-term disability. None of the patients died over the period of follow-up. These results indicate that early recognition and treatment of respiratory complications in Guillain-Barre syndrome could reduce the morbidity and mortality of this condition. (+info)
The impact of climate on the prevalence of respiratory tract infections in early childhood in Lahore, Pakistan.
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BACKGROUND: Respiratory tract infections are a major health problem in developing countries. The aim of this study was to analyse the impact of the climate on the prevalence of upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI) in four socioeconomically different groups in a developing country. METHODS: A prospective cohort study was conducted among children in four socioeconomically different groups in Lahore, Pakistan. Monthly observations were made on 1476 infants born during 1984-1987 and followed for 24 months. Prevalence of URTI and LRTI was analysed according to age, area of living, family size, time of birth, the season of the year and climate variables such as rain, temperature and humidity. RESULTS: Low monthly average minimum day temperature was associated with high prevalence of URTI and LRTI. For LRTI the impact of temperature was larger for boys, children living in larger families and children living in the poorer areas. This pattern was not seen for URTI. A peak in prevalence for LRTI was shown at 5-6 months of age for LRTI and at 10-12 months of age for URTI. CONCLUSIONS: Temperature is related to prevalence of URTI and LRTI in a developing society. The effect of temperature on health varies between different subgroups. These effects should be considered in planning health actions to prevent respiratory tract infections. (+info)
Pregenomic comparative analysis between bordetella bronchiseptica RB50 and Bordetella pertussis tohama I in murine models of respiratory tract infection.
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We describe here a side-by-side comparison of murine respiratory infection by Bordetella pertussis and Bordetella bronchiseptica strains whose genomes are currently being sequenced (Tohama I and RB50, respectively). B. pertussis and B. bronchiseptica are most appropriately classified as subspecies. Their high degree of genotypic and phenotypic relatedness facilitates comparative studies of pathogenesis. RB50 and Tohama I differ in their abilities to grow in the nose, trachea, and lungs of BALB/c mice and to induce apoptosis, lung pathology, and an antibody response. To focus on the interactions between the bacteria and particular aspects of the host immune response, we used mice with specific immune defects. Mice lacking B cells and T cells were highly susceptible to B. bronchiseptica and were killed by intranasal inoculation with doses as low as 500 CFU. These mice were not killed by B. pertussis, even when doses as high as 10(5) CFU were delivered to the lungs. B. bronchiseptica, which was highly resistant to naive serum in vitro, caused bacteremia in these immunodeficient mice, while B. pertussis, which was highly sensitive to naive serum, did not cause bacteremia. B. bronchiseptica was, however, killed by immune serum in vitro, and adoptive transfer of anti-Bordetella antibodies protected SCID-beige mice from B. bronchiseptica lethal infection. Neutropenic mice were similarly killed by B. bronchiseptica but not B. pertussis infection, suggesting neutrophils are critical to the early inflammatory response to the former but not the latter. B. bronchiseptica was dramatically more active than B. pertussis in mediating the lysis of J774 cells in vitro and in inducing apoptosis of inflammatory cells in mouse lungs. This side-by-side comparison describes phenotypic differences that may be correlated with genetic differences in the comparative analysis of the genomes of these two highly related organisms. (+info)
Chlamydia, especially Chlamydia pneumoniae, infection is closely associated with human cardiovascular diseases. Thus far, however, few experimental studies have been carried out to investigate whether natural C. trachomatis infection can induce cardiovascular pathological changes. In this article, we report that pulmonary infection with C. trachomatis mouse pneumonitis strain (MoPn) can induce myocardial and perivascular inflammation and fibrosis in C57BL/6 mice. The pulmonary MoPn infection appeared to be disseminated systemically, because chlamydial antigens were readily detectable in multiple organs including the cardiovascular tissues. In addition, gamma interferon gene knockout mice with a C57BL/6 genetic background showed significant endocarditis and pancarditis characterized by vegetation in aortic valves, interstitial and pericardial inflammatory cellular infiltration, and growth of the organisms in the heart following respiratory tract MoPn infection. The results indicate that C. trachomatis can induce cardiovascular diseases following respiratory tract infection and suggest that murine MoPn respiratory tract infection may be a useful experimental model for investigating cardiovascular diseases caused by chlamydial infection. (+info)