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PubMed2006

Mannose-binding lectin and upper respiratory tract infections in children and adolescents: a review.

OBJECTIVE: To review the literature on mannose-binding lectin (MBL) polymorphisms and susceptibility for upper respiratory tract infection (URI) in children and adolescents. DATA SOURCES: We searched PubMed from 1966 and EMBASE from 1974 to July 2005, using the terms respiratory tract infection, respiratory infection, upper respiratory infection, MBL, and mannose-binding lectin. STUDY SELECTION: Initially, 110 studies were identified. Two reviewers independently screened identified titles and abstracts. Potentially relevant studies were obtained and the full text examined. Inclusion criteria were human subjects, 18 years or younger, URI, and MBL polymorphisms. Seven of the initially identified studies met the inclusion criteria. DATA EXTRACTION: Information was gathered for each study on study design, population, possible confounders, and outcomes measured. DATA SYNTHESIS: Because there was significant heterogeneity between the identified studies, we had to describe the identified studies separately. The largest case-control studies (n = 3) as well as the cohort study (n = 1) suggest an association between MBL polymorphisms and URI, especially in young children. Results of the smaller studies (n = 3) are inconsistent. CONCLUSIONS: The association between MBL polymorphisms and URI in children remains controversial. Large prospective cohort studies with regular documentation of URI and possible confounders such as atopy and environmental factors are required to establish the role of MBL polymorphisms in susceptibility for URI.

Acute Disease↗

PubMed1987

Cigarette smoking and respiratory tract infection.

Although not conclusive, several lines of evidence suggest that cigarette smoking alters the respiratory tract's ability to defend itself from infection. Some subjects with chronic bronchitis have colonization of the lower respiratory tract with bacteria. Both patients with chronic respiratory disease and healthy smokers appear to have a higher frequency of respiratory infections and an increased severity of symptoms when infected. Children exposed passively to cigarette smoke have higher rates of respiratory illnesses. Yet the marked variability in the incidence of infection in the smoking population suggests that there are subtle factors that predispose some smokers to more risk of infection than others. Cigarette smoking is associated with alterations in mechanisms of the host defense system, even in asymptomatic individuals (summarized in Table 3). Ciliary function is impaired, mucous volume is increased, humoral response to antigens altered, and quantitative and qualitative changes in cellular components occur. Some of these alterations in host defense mechanisms are dose related; others revert to normal after smoking cessation. Yet, it is unknown if one or all of these alterations cause any significant compromise of host defense or if other factors, as yet unidentified, may be important. Answers to these questions await a more thorough elucidation of normal host defense function.

Antibody Formation↗

PubMed2001

Pharmacodynamics of fluoroquinolones against Streptococcus pneumoniae in patients with community-acquired respiratory tract infections.

Fluoroquinolone antibiotic agents have demonstrated efficacy in the treatment of respiratory tract infections. This analysis was designed to examine the relationship between drug exposure, as measured by the free-drug area under the concentration-time curve at 24 h (AUC(24))/MIC ratio, and clinical and microbiological responses in patients with community-acquired respiratory tract infections involving Streptococcus pneumoniae. The study population included 58 adult patients (34 males, 24 females) who were enrolled in either of two phase III, randomized, multicenter, double-blind studies of levofloxacin versus gatifloxacin for the treatment of community-acquired pneumonia or acute exacerbation of chronic bronchitis. Clearance equations from previously published population pharmacokinetic models were used in conjunction with dose and adjusted for protein binding to estimate individual patient free-drug AUC(24)s. In vitro susceptibility was determined in a central laboratory by broth microdilution in accordance with NCCLS guidelines. Pharmacodynamic analyses were performed on data from all evaluable patients with documented S. pneumoniae infection using univariate and multivariable logistic regression; pharmacodynamic breakpoints were estimated using Classification and Regression Tree analysis. A statistically significant (P = 0.013) relationship between microbiological response and the free-drug AUC(24)/MIC ratio was detected. At a free-drug AUC(24)/MIC ratio of <33.7, the probability of a microbiological response was 64%, and at a free-drug AUC(24)/MIC ratio of >33.7, it was 100% (P < 0.01). These findings may provide a minimum target free-drug AUC(24)/MIC ratio for the treatment of infections involving S. pneumoniae with fluoroquinolone antibiotics and provide a paradigm for the selection of fluoroquinolones to be brought forward from drug discovery into clinical development and dose selection for clinical trials. Further, when target free-drug AUC(24)/MIC ratios are used in conjunction with stochastic modeling techniques, these findings may be used to support susceptibility breakpoints for fluoroquinolone antibiotics and S. pneumoniae.

Adult↗

PubMed2002

Diagnostic tools in respiratory tract infections: use and comparison with Finnish guidelines.

The objectives of this prospective epidemiological study were to describe the diagnosis and treatment of respiratory tract infections by Finnish general practitioners and to compare current practice with national evidence-based guidelines. All patients (n = 4386) seeking primary care for a respiratory tract infection for the first time in 30 health centres during 1 week in November 1998 participated in the study. The main outcome measures were the amounts and types of diagnostic tests used and antimicrobials prescribed. Tympanometry was used in 1% of patients with acute otitis media. Ultrasonography, sinus radiography or both were used in 80% of cases of sinusitis and antigen detection or culture for Streptococci in 57% of throat infections. In acute bronchitis, a chest radiograph was taken in 5% of cases and the CRP level determined in 8%. The corresponding figures for pneumonia were 49% and 39%. In pneumonia and throat infection, diagnostic testing was statistically significantly associated with the use of antimicrobials, but not in otitis, sinusitis or acute bronchitis. Diagnostic tests were underused in respiratory tract infections compared to evidence-based recommendations.

Adolescent↗

PubMedDate not supplied

Cefixime in the treatment of patients with lower respiratory tract infections: results of US clinical trials.

Community-acquired acute lower respiratory tract infections are a common cause of illness, accounting for millions of physician visits and prescriptions each year. Cefixime is an extended-spectrum oral cephalosporin with activity against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the most commonly isolated bacterial pathogens. This review presents the results of eight US studies comparing the efficacy and safety of cefixime with those of amoxicillin, amoxicillin/clavulanate, cefaclor, cephalexin, and cefuroxime axetil in the treatment of patients with acute lower respiratory tract infections. Data for 211 cefixime-treated patients and a range of 19 to 49 patients in the comparator treatment groups were included in the efficacy analysis. Clinical success (cure or improvement) was observed in 94% of cefixime-treated patients; clinical success rates in the comparator treatment groups ranged from 97% for cefuroxime axetil and cefaclor to 79% for amoxicillin/clavulanate. At the end of treatment, the overall eradication rate in the cefixime treatment group was 92% and ranged from 76% (cefaclor) to 98% (cefuroxime axetil) in the comparator treatment groups. The percentage of persistent organisms was highest in the cefaclor (24%) and cephalexin (21%) treatment groups. With the exception of the cephalexin group (4%), the incidence of patients who reported adverse experiences was similar across treatment groups (34% to 50%). Those involving the gastrointestinal tract were by far the most common, and most adverse experiences were rated as mild or moderate in severity.

Adult↗

PubMed1982

A tracheal culture model of respiratory tract infection with Pseudomonas aeruginosa.

The pathogenesis of Pseudomonas aeruginosa for the respiratory tract has been examined using hamster tracheal organ cultures. Tracheal rings prepared from male Syrian hamsters, strain LSH/LAK, were infected with P. aeruginosa for 4 h and processed at 4-h intervals for 24 h for examination by light- and electron microscopy. Tissue destruction was observed within 8 h after infection with 10(8) colony-forming units (cfu)/ml and within 12 h after infection with 10(4) or 10(6) cfu/ml. Ciliated cells that contained abnormal subcellular organelles were expelled from the epithelium. By 20 h the epithelial borders were composed primarily of nonciliated cells. Transmission- and scanning electron microscopy revealed details of the cellular destruction and attachment of P. aeruginosa to the ciliated epithelium. Pseudomonas aeruginosa causes a rapid destruction of the epithelium of hamster trachea in cultures. Hamster tracheal organ cultures have been shown to be useful in studying the pathogenesis of P. aeruginosa for the respiratory tract.

Animals↗

PubMed1992

Neutrophil chemotactic factors in the respiratory tract of patients with chronic airway diseases or idiopathic pulmonary fibrosis.

This study was designed to clarify the contributions of specific neutrophil chemotactic factors (NCF) in neutrophil accumulation in the human respiratory tract associated with various diseases. The activity and characteristics of the NCF in the bronchoalveolar lavage (BAL) fluid and culture media of alveolar macrophages obtained from normal volunteers, control patients, patients with chronic airway diseases (CAD) and patients with idiopathic pulmonary fibrosis (IPF) were examined. The BAL fluid from normal volunteers contained NCF comparable with the chemotactic factors interleukin-8 (IL-8) and leukotriene B4 (LTB4). Analysis of the biochemical characteristics of NCF released from alveolar macrophages suggests that they are derived from alveolar macrophages. The NCF activities in BAL fluids from patients with CAD and IPF were higher than those in BAL fluids from normal volunteers and control patients. Biochemical analysis demonstrated that several kinds of NCF, including those derived from the complement component C5 and alveolar macrophages, were present in the BAL fluid from patients with CAD and respiratory infections. The especially marked increase of C5-derived NCF indicate their importance in neutrophil accumulation in the respiratory tract of patients with CAD. Alveolar macrophages released different types of NCF after different lengths of culture periods (4 h and 24 h). Alveolar macrophages from patients with IPF released larger amounts of NCF than alveolar macrophages from normal volunteers, indicating the importance of alveolar-macrophage-derived NCF as well as C5-derived NCF in neutrophil accumulation in the respiratory tract of patients with IPF. These results suggest that various types of NCF increase in response to different disease states of the respiratory tract and serve to regulate the accumulation of neutrophils.

Adult↗

PubMed1980

Nickel-related cancers of the respiratory tract.

Nickel-related cancers of the respiratory tract have been recognized for nearly 50 years and represent a unique opportunity for prevention among refinery workers. Studies of exposed employees have been conducted in which evaluations were made of the histopathologic changes in the respiratory mucosa and the body burden of nickel was measured by regular plasma nickel determinations. The sites of tumor predilection are related to airflow patterns of the nose and tracheobronchial tree. The metaplastic changes in these areas are accompanied by increased tissue concentrations of nickel. Close monitoring of nickel workers has led to a lower incidence of respiratory cancers and earlier diagnosis.

Adult↗

PubMed1990

Comparison of oral erythromycin ethylsuccinate and ciprofloxacin in the treatment of acute respiratory tract infections.

A total of 619 patients with acute upper or lower respiratory tract infection were randomised to receive either erythromycin ethylsuccinate tablets at a dose of 1 g twice daily, or ciprofloxacin tablets 500 mg twice daily in a single-blind, multicentre study. The efficacy of each antibacterial was similar, with close to 90% of patients on each treatment being reported as either cured or improved. Gastrointestinal symptoms were the most commonly reported side-effects, being similar in overall incidence for both agents. Nausea, vomiting, dizziness and headache occurred more frequently in the ciprofloxacin group, while abdominal pain and diarrhoea occurred more frequently in the erythromycin ethylsuccinate group. In each group, the number of patients failing to complete treatment was similar and the main reasons cited for discontinuation were gastrointestinal symptoms. This study indicates that both erythromycin ethylsuccinate and ciprofloxacin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections.

Adolescent↗

PubMed1993

[Incidence of fungal isolation in clinical specimens from the respiratory tract].

The incidence of fungal isolation in 711 clinical specimens from the respiratory tract was investigated in 159 patients with pulmonary diseases. Fungi were isolated from 14/19 pharynx swab samples, 246/342 sputum samples, 34/147 bronchial aspirate samples, 18/97 bronchial lavage samples, 4/17 transbronchial lung biopsy samples, and 5/60 plugged catheter brush samples. Contamination by fungi in normal flora was prevented by using an aseptic procedure for sampling specimens from the respiratory tract. The isolation rate of Candida spp. from sputum was 70.0% (C. albicans: 151 strains, C. glabrata: 43 strains, C. tropicalis: 25 strains, C. lusitaniae: 4 strains, C. krusei: 3 strains, C. guilliermondii: 3 strains and C. paraspilosis: 1 strain). The isolation rates of C. neoformans and A. fumigatus from sputum were 6.4% and 8.8%, respectively. Isolated fungi from bronchial aspirate included 12 strains of C. albicans, 6 strains of C. tropicalis, 5 strains of A. fumigatus and 2 strains of C. neoformans. Isolated fungi from bronchial aspirate revealed 6 strains of C. albicans, 2 strains of C. glabrata, 1 strain of C. neoformans and 6 strains of A. fumigatus. The isolation rates of fungi from sputum obtained from patients with pulmonary aspergilloma and cryptococcosis were 66.5% and 50.0%, respectively. The isolation rate of fungi from sputum of patients with underlying diseases was higher than that of patients with no underlying disease.

Adolescent↗

PubMed1995

Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen in adults.

Corynebacterium pseudodiphtheriticum has been reported to be an uncommon respiratory pathogen. We describe the clinical and microbiologic features of 17 patients from whose sputum C. pseudodiphtheriticum was isolated. Patients were identified through a review of the reports from the clinical microbiology laboratory at York Hospital, a community teaching hospital, from October 1990 through April 1993; 17 patients with respiratory infection caused by C. pseudodiphthriticum were identified. There were 12 cases of bronchitis and five of pneumonia. An underlying systemic condition, particularly congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, or malignancy, was common. Onset of symptomatology was acute for most patients, but fever was noticeably absent in almost two-thirds of the cases. Isolates were uniformly susceptible to the beta-lactam antibiotics, vancomycin, and trimethoprim-sulfamethoxazole, but resistance to clindamycin and erythromycin was common. The isolation of diphtheroids from a properly obtained sputum sample from a patient with respiratory tract infection should not always be dismissed as due to contamination. The isolation, identification, and susceptibility testing of C. pseudodiphtheriticum from respiratory tract specimens may provide information useful for treatment of patients.

Adult↗

PubMed1989

[Controlled multicentric study comparing cefixime and amoxicillin in the treatment of lower respiratory tract infections in adults].

This multicentre, randomized, double-blind study evaluated the effectiveness and safety of cefixime versus amoxicillin. Patients were admitted if they had lower respiratory tract infection with a bacterial pathogen susceptible to both study drugs. Diagnoses included acute respiratory tract infections with no underlying pulmonary pathology (cefixime 21, amoxicillin 27), acute exacerbation of chronic obstructive lung disease (cefixime 32, amoxicillin 42), superinfection of viral bronchitis or lung cancer, and pleuritis (cefixime 10, amoxicillin 6). Patients were treated for at least 10 days with either cefixime 200 mg b.d. or amoxicillin 1 g b.d. A clinical success rate of 80.7 per cent (50/62) in the cefixime group and 82.2 per cent (60/73) in the amoxicillin group was achieved in infections due to susceptible organisms. In acute infections with no underlying pathology, the clinical success rate was 90.5 per cent with cefixime and 81.5 per cent with amoxicillin. Twenty-three cefixime patients and 20 amoxicillin patients were seen 2 to 6 weeks after treatment: there were 2 and 1 clinical recurrences, respectively. All 3 patients were suffering from chronic obstructive lung disease. The bacteriological eradication rate at the end of treatment in assessable patients was 94.7 per cent (17/18) with cefixime and 80 per cent (16/20) with amoxicillin. Six and 11 new organisms appeared, responsible for 2 superinfections under cefixime and 7 under amoxicillin. Treatment was well tolerated by 96.4 per cent of cefixime patients and 90 per cent of amoxicillin patients. This study confirms the value of cefixime as a new oral antibiotic in the treatment of lower respiratory tract infections in adults.

Adolescent↗

PubMed2001

Dosimetry modeling of inhaled formaldehyde: the human respiratory tract.

Formaldehyde (HCHO), which has been shown to be a nasal carcinogen in rats and mice, is used widely and extensively in various manufacturing processes. Studies in rhesus monkeys suggest that the lower respiratory tract may be at risk and some epidemiologic studies have reported an increase in lung cancer associated with HCHO; other studies have not. Thus, an assessment of possible human risk to HCHO exposure based on dosimetry information throughout the respiratory tract (RT) is desirable. To obtain dosimetry estimates for a risk assessment, two types of models were used. The first model (which is the subject of another investigation) used computational fluid dynamics (CFD) to estimate local fluxes in a 3-dimensional model of the nasal region. The subject of the present investigation (the second model) applied a 1-dimensional equation of mass transport to each generation of an adult human symmetric, bifurcating Weibel-type RT anatomical model, augmented by an upper respiratory tract. The two types of modeling approaches were made consistent by requiring that the 1-dimensional version of the nasal passages have the same inspiratory air-flow rate and uptake during inspiration as the CFD simulations for 4 daily human activity levels. Results obtained include the following: (1) More than 95% of the inhaled HCHO is predicted to be retained by the RT. (2) The CFD predictions for inspiration, modified to account for the difference in inspiration and complete breath times, are a good approximation to uptake in the nasal airways during a single breath. (3) In the lower respiratory tract, flux is predicted to increase for several generations and then decrease rapidly. (4) Compared to first pulmonary region generation fluxes, the first few tracheobronchial generations fluxes are over 1000 times larger. Further, there is essentially no flux in the alveolar sacs. (5) Predicted fluxes based on the 1-dimensional model are presented that can be used in a biologically based dose-response model for human carcinogenesis. Use of these fluxes will reduce uncertainty in a risk assessment for formaldehyde carcinogenicity.

Animals↗

PubMed2004

Evaluation of the association between atypical bacteria infections and respiratory tract diseases with emphasis on bronchial asthma exacerbations in children.

Mycoplasma pneumoniae and Chlamydia pneumonie are important etiological agents responsible for human respiratory tract diseases. Recently, these atypical microorganisms received much attention regarding their role in bronchial asthma pathogenesis, which is one of the most frequent chronic diseases in children. The aim of the study was to investigate the association between infections caused by these pathogens and respiratory tract diseases in children. Levels of M. pneumoniae and C. pneumoniae-specific antibodies were determined in serum samples obtained from 30 patients suffering from bronchial asthma exacerbations, 10 patients with pneumonia, 28 patients with chronic otitis media with effusion (COME) and 22 sinusitis patients. Specific anti-M. pneumoniae antibodies were detected more frequently in the patients enrolled in the study than in control subjects. The highest percentage of the serum samples, which demonstrated the presence of M. pneumoniae-specific antibodies was demonstrated in patients with asthma (60%) and it was twofold higher than in control subjects. Serologic profile of 26.6% patients with asthma, 50% of patients with pneumonia, 39.2% of patients with COME, 45.4% of patients with sinusitis and 10% of control subjects was consistent with a possible acute infection caused by M. pneumoniae. The presence of specific anti-C. pneumoniae antibodies was demonstrated in a smaller percentage of patients--in 13.3% of children with asthma, 10% of children with pneumonia and in 7.1% of patients with COME; the level of specific antiobodies was suggestive of acute chlamydial infection only in COME patients. Analysis of serologic markers for atypical bacteria infections indicates a possible association between infections caused by M. pneumoniae and bronchial asthma exacerbations and other respiratory tract disorders including pneumonia, sinusitis and COME.

Adolescent↗

PubMed2006

Compliance of clinical microbiology laboratories in the United States with current recommendations for processing respiratory tract specimens from patients with cystic fibrosis.

Respiratory tract specimens from patients with cystic fibrosis (CF) require unique processing by clinical microbiology laboratories to ensure detection of all potential pathogens. The present study sought to determine the compliance of microbiology laboratories in the United States with recently published recommendations for CF respiratory specimens. Microbiology laboratory protocols from 150 of 190 (79%) CF care sites were reviewed. Most described the use of selective media for Burkholderia cepacia complex (99%), Staphylococcus aureus (82%), and Haemophilus influenzae (89%) and identified the species of all gram-negative bacilli (87%). Only 52% delineated the use of agar diffusion assays for susceptibility testing of Pseudomonas aeruginosa. Standardizing laboratory practices will improve treatment, infection control, and our understanding of the changing epidemiology of CF microbiology.

Bacteria↗

PubMed1978

Respiratory tract epithelium in primary culture: concurrent growth and differentiation during establishment.

Studies of cellular function in the respiratory tract lining have traditionally been limited by the small tissue mass and functional diversity of the epithelium. Recent improvements in culture conditions have permitted long-term maintenance of epithelial cells derived from the upper respiratory tract of rats. The present study determined the extent to which proliferation and differentiation took place in such epithelial cell cultures. The labelling index obtained after 3H-dThd administration was approximately 100-fold higher than that of the quiescent epithelium in vivo; therefore, a large proportion of the cells were probably in the cycling population. Ultrastructural studies showed that features unique to the specialized mucous secretory cells and ciliated cells were lost rapidly with entry of these cells into the in vitro environment. With long-term maintenance, the cultures were reorganized into a stratified epithelium containing large, squamous, apical cells and small basal cells. The ultrastructural appearance of basal cells in vitro was nearly identical to that of basal cells in vivo. Squamous cells were frequently joined by tight junctions. Because hemicysts originated by detachment of squamous cells from the basal layers but not from adjacent squamous cells, they were considered to indicate stratification in the cultures. The proliferative and differentiative status of the mucociliary epithelium was altered by in vitro conditions, and came to resemble that of early squamous metaplasia in the respiratory tract epithelium.

Animals↗

PubMed1980

The immotile cilia syndrome--one cause of persistent upper respiratory tract infection.

Four patients with persistent recurrent upper respiratory tract infections are presented. Electron microscopic studies of respiratory mucosal biopsies from these patients reveal ultrastructural abnormalities of cilia consisting of partial to complete loss of dynein arms, radial spoke disruption, and compound cilia. The concept of immotile cilia as an important cause of recurrent infections is receiving more attention. This study stresses the need for simple, rapid screening tests for cilial activity followed by electron microscopic evaluation in selected cases.

Biopsy↗

PubMed1987

[Flomoxef treatment of patients with respiratory tract infections].

Flomoxef (FMOX, 6315-S) was administered to 22 patients with respiratory tract infections. The patients consisted of 13 patients with pneumonia, 7 with bronchitis, 1 with bronchiectasis and 1 with pyothorax. The drug was administered by intravenous injection or intravenous drip infusion twice a day with doses of 1 to 2 g and total doses ranged from 17 to 64 g. The following results were obtained. 1. Clinical responses to the therapy were excellent in 1 case, good in 10 cases, fair in 4 cases, poor in 4 cases and not determined in 3 cases. Efficacy ratio was 57.9%. 2. As for adverse reactions, exanthema in 1 patient and stomatitis and numbness of tongue in another patient were observed, but these symptoms improved with cessation of the therapy. Abnormal laboratory test values were observed in 5 cases. From these results it appears that FMOX is a valuable antimicrobial agent against patients with respiratory tract infections.

Aged↗