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IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis.

The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators. Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -70 degrees C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity. In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0-153) versus 0 (0-5.6) ng x mL(-1)) HNE (136 (32-694) versus 14 (0-516) ng x mL(-1)) and elastase activity (4 (1-220) versus 1 (0-339) mU x mL(-1)) were found. These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease.

Acute Disease↗

Increase in proteinuria and/or microhematuria following upper respiratory tract infections in patients with IgA nephropathy.

Exacerbation of urinary abnormalities after upper respiratory tract infections in patients with IgA nephropathy was examined. Twenty patients with IgA nephropathy and fourty patients with other glomerular diseases were evaluated in this study. The incidence of exacerbation in microhematuria after upper respiratory tract infections was significantly higher in patients with IgA nephropathy than those with other glomerular diseases. The improvement of microhematuria after upper respiratory tract infections was significantly delayed in some patients with IgA nephropathy. It is indicated that upper respiratory tract infections might be a risk factor of exacerbation in patients with IgA nephropathy.

Glomerulonephritis↗

Use of Echinacea in upper respiratory tract infection.

The significant burden of upper respiratory tract infection in adults and children, coupled with a lack of specific treatment options, invites the use of alternative therapies. Echinacea is an herb widely used for the prevention or treatment of upper respiratory tract infection. This review article examines the mechanism of action, dose, and types of Echinacea used for these purposes. The principal mode of action of Echinacea is through immunostimulation. Most Echinacea studies were done in Germany, but their results are difficult to interpret because of variability of experimental parameters. Types of Echinacea commonly used are Echinacea purpurea, E pallida, and E angustifolia. Both the plant's upper parts and roots are used. For oral administration, tablets, extracts, fresh pressed juice, teas, and tinctures have been used. Though studies show a beneficial effect, clear conclusions and recommendations of Echinacea use cannot be made due to a lack of standard product, variability in dose, and variability in outcome measures. Therefore, well-designed studies with consistent standardized measures are required.

Adult↗

[Metapneumoviruses--the "youngest" pathogens of respiratory tract infections in human].

Acute respiratory infections are the most common diseases in all age groups in the world. Lower respiratory infections are the main reason of death, hospitalization and antibiotic use in immunocomprised patients and/or patients with respiratory system chronic diseases. The leading role plays viruses: rhinoviruses, influenza and parainfluenza viruses, respiratory syncytial viruses (RSV), adnenoviruses and coronaviruses. The "youngest" pathogen in this group are human metapneumowiruses (hMPV), identified in 2001. They are the reason of infections in infants, older adults and immunocomprised patients. Manifestation of the infection can have a form from a self-limiting upper respiratory tract inflammation, through bronchitis (in adults), bronchiolitis (in infants) and pneumonitis (in infants and adults), and extremely of severe acute respiratory failure with a need of mechanical ventilation. The authores describe microbiological, epidemiological and clinical features on infection with hMPVs.

Aged↗

Antimicrobial agents for community-acquired respiratory tract infections.

Chemotherapy of community-acquired respiratory tract infections was reviewed from a microbiological perspective. The current worldwide spread of penicillin-resistant Streptococcus pneumoniae and of ampicillin-resistant Haemophilus influenzae has required a reassessment of the antimicrobial agents being used for empiric therapy. In vitro data with different orally administered antibiotics were reviewed in order to identify any deficiencies in their spectra of activity against four common respiratory tract pathogens. Cefixime, cefuroxime axetil, cefprozil, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole were active against all four species other than penicillin-resistant pneumococci.

Ampicillin Resistance↗

Upper respiratory tract infections in young children: duration of and frequency of complications.

This study was performed to determine the usual duration of community-acquired viral upper respiratory tract infections and the incidence of complications (otitis media/sinusitis) of these respiratory tract infections in infancy and early childhood. Children in various forms of child-care arrangements (home care, group care, and day care) were enrolled at birth and observed for 3 years. Families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval. Only children remaining in their original child-care group for the entire study period were compared. The mean duration of an upper respiratory tract infection varied between 6.6 days (for 1- to 2-year-old children in home care) and 8.9 days (for children younger than 1 year in day care). The percentage of apparently simple upper respiratory tract infections that lasted more than 15 days ranged from 6.5% (for 1- to 3-year-old children in home care) to 13.1% (for 2- to 3-year-old children in day care). Children in day care were more likely than children in home care to have protracted respiratory symptoms. Of 2741 respiratory tract infections recorded for the 3-year period, 801 (29.2%) were complicated by otitis media. During the first 2 years of life, children in any type of day care were more likely than children in home care to have otitis media as a complication of upper respiratory tract infection. In year 3, the risk of otitis media was similar in all types of child care.

Age Factors↗

Tannic acid supplemented fixation improves ultrastructural evaluation of respiratory epithelium in children with recurrent respiratory tract infections.

Samples of the respiratory mucosa of children with recurrent respiratory infections suspected of having primary ciliary dyskinesia are routinely fixed with glutaraldehyde before ultrastructural examination. This standard technique, however, may not be optimal for visualizing ciliary components or for preserving several cellular and extracellular structures during dehydration and embedding procedures. In this study, brushes of nasal (28 samples) and/or tracheal (9 samples) mucosa from 32 children with recurrent respiratory tract infections were examined. Twenty-nine samples were fixed with glutaraldehyde supplemented with tannic acid to determine if the ultrastructural analysis of respiratory epithelium and bronchial secretions could be improved. Eight samples were conventionally fixed with glutaraldehyde alone. Lesions of the cellular membrane and damaged cells were easily visualized using tannic acid supplemented fixation. Internal ciliary structures including individual microtubules and dynein arms were also more clearly observed. In addition, the internal structure of microvilli of the respiratory epithelium could be studied and the presence of phospholipid-rich surfactant-like material within nasal and tracheal secretions were visualized after tannic acid supplemented fixation. We suggest that addition of tannic acid during fixation is useful for accurate ultrastructural evaluation of respiratory mucosa in both clinical and experimental situations.

Adolescent↗

Herpes simplex virus infection of the adult lower respiratory tract.

We have reported six adult patients with HSV infection of the lower respiratory tract diagnosed ante-mortem, and have reviewed the literature on this subject. An attempt has been made to define the natural history of the infection, and suggestions have been made regarding diagnosis and treatment. HSV can infect the lower respiratory tract in immunologically normal patients, as well as the immunocompromised host. Many patients have been burned, or intubated, or have other reasons for squamous metaplasia of the respiratory epithelium. The pathogenesis in many cases is an extension or aspiration of oropharyngeal HSV, but there is a suggestion that some cases may be hematogenously spread. The diagnosis of the site and presence of HSV infection should be based initially on cytologic findings, histologic findings, or both. Viral cultures or immunofluorescent or immunoperoxidase labeling can be used to confirm the cytologic and histologic diagnoses. Bronchoscopy is valuable for visualizing ulcerations or membranes in the respiratory tract, and for improving the sensitivity and specificity of the cytologic diagnosis. Because the process is most often focused in the tracheobronchial tree, percutaneous needle biopsy and open lung biopsy may be less sensitive than bronchoscopy. Standard serologic tests are, in general, not helpful diagnostically. They can help verify that a recent HSV infection has occurred, but do not differentiate between primary and recurrent infection, and do not help in localizing the site of infection. However, paired complement fixation or neutralizing antibody titers may be useful prognostically. If the titers do not rise in the presence of a documented HSV lower respiratory tract infection, the outcome is more likely to be fatal. The respiratory epithelium from the oral mucosa to the alveoli can be infected with HSV. The manifestations can range from a few scattered ulcers in the trachea to a severe ulcerative process resulting in an obstructing, inflammatory tracheobronchial membrane. Focal or diffuse pneumonia can also occur. No specific treatment for the illness can be recommended at this time. There is no evidence that currently available antiviral therapy is effective. The outcome of the illness seems to be largely dependent on the immunologic status of the host, complicating superinfections, and the progression of the underlying disease.

Adult↗

Antimicrobial susceptibility patterns of respiratory tract pathogens from sheep and goats.

OBJECTIVE: To determine the antimicrobial susceptibility of common respiratory tract pathogens from sheep and goats. DESIGN: Cross-sectional study. SAMPLE POPULATION: 41 respiratory tract isolates from sheep and 36 isolates from goats. PROCEDURES: Disk diffusion assay was used to determine antimicrobial susceptibility of isolates to amoxicillin-clavulanic acid, ceftiofur, ciprofloxacin, florfenicol, and tetracycline. Minimum inhibitory concentrations of florfenicol for these isolates were determined by use of the microbroth dilution technique. RESULTS: The most common isolates were Pasteurella multocida (n = 28) and Mannheimia haemolytica (39). All isolates were susceptible to amoxicillin-clavulanic acid, ceftiofur, ciprofloxacin, and florfenicol. Five percent (4/77) of isolates were resistant to tetracycline. CONCLUSIONS AND CLINICAL RELEVANCE: Susceptibility of respiratory tract pathogens isolated from sheep and goats to commonly used antimicrobial drugs in this study was high. Treatment of these species for bacterial respiratory tract disease is likely not complicated by antimicrobial resistance.

Animals↗

[Respiratory tract infections in the elderly, advances and limitations in the diagnosis and treatment].

Advances and limitations in the diagnosis and treatment of respiratory tract infections were discussed in relation to the prognosis of the elderly patients. Haemophilus influenzae and Streptococcus pneumoniae are the major pathogens in the community-acquired respiratory tract infections. On the other hand, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the major pathogens in the nosocomial respiratory tract infections. Detection of MRSA-PBP genes and antibiotic sensitivity tests are important for the diagnosis of MRSA. Vancomycin or arbekacin is the first-choice antibiotic for the treatment of severe infection caused by MRSA, and a combination therapy using one of the above agents and a partner antibiotic is necessary in some cases of MRSA infections. Reports concerning the significance of anaerobic bacteria in respiratory tract infections in Japan have been rare, presumably because procedures to recover anaerobic bacteria from specimens other than sputum, for example transtrancheal aspiration (TTA), bronchoscopic procedure and transcutaneous lung biopsy, are required for the diagnosis of the anaerobic respiratory tract infections. Nowadays, identification of cytomegalovirus (CMV) is a prerequisit for the rapid diagnosis of CMV infection. Therefore attempts are being made to detect a specific substance, for example messenger RNA during the stage of reactivation of CMV. Prophylaxis as well as treatment is necessary for the control of acute exacerbation of chronic respiratory tract infections. In this regard, long-term administration of a small dose of erythromycin or new-quinolone is promising.

Aged↗

Preoperative assessment of the likelihood of infection of the lower respiratory tract after cardiac surgery.

Lower-respiratory-tract infections are among the most frequent complications observed in the intensive care unit, leading to delayed postoperative recovery time and increased costs and mortality. We have tried to evaluate the prognostic value of perioperative bacteriology of tracheal aspirates in assessing the risk of such complications. In a prospective study aspirates of 100 patients undergoing cardiac surgery were taken immediately after intubation and were analysed for microorganisms by Gram-stain and microbiological cultures using standard procedures. All patients received perioperative antibiotic prophylaxis with a single dose of 2 g ceftriaxone intravenously. From 26 patients with bacteriologically positive tracheal secretion, 8 (30.7%) developed lower respiratory tract infection whereas only 1 of 72 patients (1.4%) with negative bacteriological results developed this complication. Smoking (p less than 0.01) and abnormal preoperative lung function (p less than 0.01) were significantly more frequent in patients developing postoperative pneumonia. Regarding the results of this study, the risk of developing pulmonary infection in the early postoperative course after cardiac surgery can be estimated from the tracheal aspirates.

Adult↗

Adherence of microorganisms in infections of the respiratory tract.

Although upper respiratory infections are a cause of significant morbidity, the mechanism by which microorganisms have a toxic effect on these mucosal surfaces is only beginning to be understood. Human and animal research has indicated that microbial adherence to the host cell is one of the initial elements responsible for microbial toxicity to respiratory and gastrointestinal epithelium. The role played by adherence is governed by a variety of host and microbial factors. A clearer understanding of the role of these factors should help to promote methods of interfering with this toxic process and thus limit morbidity produced by these infections.

Adhesiveness↗

Coordinated expression of Hoxb genes and signaling molecules during development of the chick respiratory tract.

To elucidate the molecular mechanism for regulating the region-specific morphogenesis of the chicken respiratory tract, we analyzed the spatiotemporal expression patterns of the Hoxb genes, Bmp-2, Bmp-4, Wnt-5a, and Wnt-11 in the developing respiratory tract. We found region-specific expression of these genes in the mesenchymal layer of the respiratory tract. Before bronchial branching proceeds, Hoxb genes show nested expression patterns around the ventral-distal tip of the lung bud. As morphogenesis proceeds, these expression domains correspond to the morphological subdivisions of the chick respiratory tract. Hoxb-5 and Hoxb-6 expression domains demarcate the trachea, bronchial tree, and air sacs. Particularly the expression domains of Hoxb-6 to -9 correspond to the morphological subdivisions of the air sacs along the proximodistal axis. Bmp-4 and Bmp-2 are expressed throughout the entire pulmonary mesenchyme and its dorsal half, respectively. Wnt-5a and Wnt-11 are expressed in the tracheal mesenchyme. Interestingly, the expression domain of Bmp-2 is complementary to the Hoxb-6 domain. The respiratory mesenchyme influences the process of epithelial branching during morphogenesis. By tissue recombination experiments, we found that the dorsal and the ventral pulmonary mesenchyme, demarcated by Hoxb-6 expression, have different inductive capacities toward the tracheal epithelium. These observations suggest the possibility that Hoxb genes are involved in the system specifying regional differences in morphogenesis and cytodifferentiation of respiratory tract. In addition, it is possible that BMPs and WNTs mediate region-specific epithelial-mesenchymal interaction in this system.

Animals↗

Effects of the respiratory tract on inhaled materials.

Inhalation exposure is often compared to intravenous or oral routes of administration with regard to the biological fate of inhaled materials. Such comparisons, however, overlook the contribution of respiratory tract enzymes to the metabolic fate and toxicity of inhaled materials. The effect of respiratory tract metabolism on the toxicity of inhaled materials is thought to be substantial for many compounds for the following reasons. (1) High concentrations of xenobiotic metabolizing enzymes occur in the nose and substantial concentrations occur in the lung. (2) The respiratory tract tissues are the first exposed to inhaled materials and are exposed to the highest concentrations (barring tissue specific uptake). (3) The products of respiratory tract metabolism may have different toxicities from those of hepatic metabolism. (4) Tissues at risk to toxic metabolites formed in the respiratory tract are different from those formed in the liver. These four reasons for concluding that respiratory tract metabolism may influence the toxicity of inhaled materials are backed by a solid body of expanding experimental data. Therefore, a complete assessment of the fate of inhaled materials should include assessment of potential contributions of respiratory tract metabolism.

Administration, Inhalation↗

[Treatment of acute infections of the lower respiratory tract in children].

INTRODUCTION: Acute respiratory tract infections are the most common childhood diseases. A preschool child suffers up to 5-7 infections of upper airways during a year. Lower airway infections make 5-20% of all respiratory infections. ETIOLOGIC FACTORS: In developed countries, 75% of pneumonias in childhood are of viral etiology, in 15% of bacterial, and in 10% of some other causative agent (mycoplasma, rickettsiae, fungi, parasites). In developing countries, bacterial pneumonias are present in much higher percentages. TREATMENT: Treatment of respiratory infections includes antimicrobial therapy (causal), relief of symptoms (symptomatic) and conduction of general principles in child treatment. The choice of antimicrobial drug is based on evidence of agents and their sensitivity to antimicrobial drugs, age, patient's condition, previous treatment and possible allergic reactions to the drug. In cases where we cannot provide adequate specimen for microbiologic testing, when these tests do not reveal the agent, or when therapy must be started before the agent is available, we must decide about the therapy, taking in consideration the most frequent agents, and those that would cause the most devastating clinical picture. This therapy can later be modified according to the isolated agent and its sensitivity to the drug. CONCLUSION: Having in mind the incidence and importance of respiratory infections in morbidity and mortality of children, the aim of this article was to show guidelines in treatment of respiratory infections in children. The main point remains that we should take in consideration the individual patient before all.

Acute Disease↗

Effects of inhalation exposure to propylene oxide on respiratory tract, reproduction and development in rats.

Nasal, respiratory, reproductive and developmental toxicities of propylene oxide (PO) were examined by exposing male and female Sprague-Dawley rats to PO vapor by inhalation at a concentration of 0 (control), 125, 250, 500 or 1,000 ppm for 6 h/d, 7 d/wk, during a 5- to 6-wk period, including premating, mating and postmating or gestation. The inhalation exposure to 1,000 ppm PO seriously affected parental survival, the upper and lower respiratory tract, male and female reproductive systems, motor function, and fetal survival and development, whereas the exposure to 500 ppm or less primarily caused nasal lesions without any sign of reproductive or developmental toxicity. Because atrophy of the olfactory epithelium in the male rats exposed to 250 ppm was the most sensitive endpoint for PO toxicity, the NOAEL was determined to be 125 ppm for the nasal endpoint. An additional inhalation experiment was carried out to further examine developmental toxicity by exposing pregnant rats to 0, 125, 250, 500, 750 or 1,000 ppm PO during a 2-wk period of gestation, Day 6 through Day 19. The 2-wk inhalation experiment revealed that reduced fetal body weights and delayed ossification occurred in association with significantly reduced body weights of the dams exposed to 750 and 1,000 ppm, whereas neither fetal death nor teratogenicity occurred at those two exposure levels. It was concluded that the developmental toxicity of fetal death was manifested at parentally toxic exposure levels above 500 ppm, a level which seriously affected parental survival, the upper and lower respiratory tracts and reproductive system.

Animals↗

[Clinical evaluation of sultamicillin in lower respiratory tract infections].

Clinical efficacy and safety of sultamicillin (SBTPC) in patients with lower respiratory tract infections, mainly pneumonia and bronchitis, have been evaluated in a multicenter trial by 19 institutions in the Kyushu area during a period of 12 months from December 1988 to November 1989. 1. Clinical evaluation was made in 132 patients and efficacy rates of SBTPC were 80.0% (28/35) for pneumonia, 78.5% (73/93) for bronchitis and 100% for the remaining 1 patient with other respiratory tract infections. The overall efficacy rate was 79.1% (102/129). 2. Clinical efficacy rate of SBTPC for respiratory tract infections in patients with underlying diseases such as chronic bronchitis, old pulmonary tuberculosis etc., was 75.0% (60/80) which was not significantly different from the efficacy rate of 85.7% (42/49) in patients without underlying diseases. 3. Of 13 patients who failed to respond to previous antibiotic treatments, 8 (61.5%) were effectively treated with SBTPC. 4. Clinical efficacy rates against infections caused by single species of organisms were 90.9% (10/11) for Haemophilus influenzae, 100% (8/8) for Streptococcus viridans and 100% (3/3) for Staphylococcus aureus. The overall clinical efficacy rate in all cases of monomicrobial infections was 88.6% (31/35), in polymicrobial infection 45.5% (5/11) and the overall efficacy rate in cases in which causative bacteria were identified was 78.3% (35/46). 5. Adverse reactions occurred in 6.8% (9/132) of the patients. The symptoms included allergic reaction in 1 patient, gastrointestinal system disorders in 7 patients and general fatigability in 1 patient. As abnormalities in laboratory test values, elevations of A1-P, GOT, and GPT were observed in 3 patients during the study, but returned to normal after discontinuation of SBTPC administration. 6. SBTPC is a useful antibiotic in the treatment of lower respiratory tract infections under the current medical environment where resistant organisms which produce beta-lactamases have been increasing.

Adolescent↗

Therapeutic potential of the new quinolones in the treatment of lower respiratory tract infections.

The impact of respiratory infections on public health is increasing and lower respiratory tract infections are a major cause of morbidity and mortality. We are also facing a worldwide burst of antibiotic bacterial resistance. The new fluoroquinolones have an excellent spectrum covering the most important respiratory pathogens, including atypical and 'typical' pathogens. Pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained postantibiotic effect. Fluoroquinolones combine exceptional efficacy with cost-effectiveness. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of community-acquired pneumonia. This review discusses the more recent data on bacteriological and clinical activity and critically analyses the risks of a potential overuse of this valuable new class of drugs.

4-Quinolones↗