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PubMed2000

Bactericidal activity of a monocytic cell line (THP-1) against common respiratory tract bacterial pathogens is depressed after infection with respiratory syncytial virus.

Non-typable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and respiratory syncytial virus (RSV) are commonly isolated from patients during the course of chronic obstructive pulmonary disease (COPD). Earlier studies found that virus infection enhanced binding of bacterial respiratory pathogens to epithelial cells in vitro. The objective of the present study was to assess the effect of RSV infection of a human monocytic cell line on bactericidal activity and cytokine production in response to these bacterial respiratory pathogens. The effect of RSV infection on binding, uptake and intracellular killing of bacteria by a human monocytic leukaemia cell line, THP-1, was assessed. Cell culture supernates were examined with a mouse fibroblast cell assay for tumour necrosis factor-alpha (TNF-alpha) bioactivity. Expression of CD14, CD11a, CD18, CD15 and CD29 on uninfected and RSV-infected THP-1 cells was assessed by flow cytometry in relation to differences in bacterial binding. RSV infection of THP-1 cells significantly decreased their ability to bind and kill bacteria. Compared with uninfected cells, fewer bacteria bound to RSV-infected THP-1 cells and the surface antigens that have been reported to bind bacteria were expressed at lower levels on RSV-infected cells. RSV-infected cells incubated with bacteria exhibited less TNF-alpha bioactivity than uninfected cell incubated with bacteria. The results elucidate some of the mechanisms involved in the increased susceptibility of virus-infected patients to secondary bacterial infection. Reduced bacterial killing by virus-infected monocytes might contribute to reduced clearance of bacteria from the respiratory tract and damage elicited by the bacteria or cytokine response in COPD patients.

Antibodies, Monoclonal↗

PubMed2003

Ketolides: a new class of antibacterial agents for treatment of community-acquired respiratory tract infections in a primary care setting.

Pathogens implicated in community-acquired respiratory tract infections are becoming increasingly resistant to anti-bacterial therapies. Thus, there is an urgent need for new agents with activity against current resistant respiratory tract pathogens and a low potential to select for resistance or induce cross-resistance to existing antibacterial agents. Telithromycin, the first ketolide antibacterial agent to undergo clinical development, has enhanced binding to bacterial ribosomal RNA. Through its unique structure, telithromycin retains activity against resistant respiratory pathogens and has shown high efficacy in the treatment of respiratory tract infections. On the basis of phase 3 clinical trial experience, telithromycin appears safe and well tolerated across various patient populations, including high-risk groups.

Anti-Bacterial Agents↗

PubMed2002

Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients.

In human immunodeficiency virus (HIV)-infected patients, bacterial lower respiratory tract infections are the most frequent respiratory diseases. They are frequently the first clinical manifestation of HIV infection. The incidence and severity of bacterial lower respiratory tract infections increase with the degree of immunosuppression. At the acquired immune deficiency syndrome (AIDS) stage, the responsible bacteria and clinical presentation may be atypical. Bacterial pneumonia may be fatal, particularly in AIDS patients, and its occurrence is predictive of a reduced survival time. Pneumococcal vaccine is recommended in patients with a CD4 T-lymphocyte count of > 200 cells mm(-3) and cotrimoxazole (trimethoprim/sulfamethoxazole) in patients with a CD4 T-lymphocyte count of < 200 cells x mm(-3). Unfortunately, such prophylaxis remains insufficiently prescribed and its protective effect is limited. Highly active antiretroviral treatment has dramatically reduced the incidence of lower respiratory tract infection due to Pseudomonas aeruginosa and opportunistic bacteria. In contrast, successful highly active antiretroviral therapy slightly decreased the risk of bacterial pneumonia due to usual bacteria, even in patients on successful highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

PubMed1986

[Effects of ambroxol on pulmonary surfactant--analysis of the fatty acid composition of phosphatidylcholine in the sputum and normal respiratory tract fluid in rabbits].

The mechanism of action of secretagogic expectorants (ex., ambroxol) has not been clarified. Recently, attention has been directed to the relationship of their action to pulmonary surfactants. In the present study, the fatty acid (FA) composition of phosphatidylcholine (PC), which is the main physiological surfactant, was investigated using sputum, respiratory tract fluid, mucin-like substance, lung washings and lung tissue of rabbits. Effects of ambroxol (20 mg/kg, i.s.) on several parameters such as output volume, FA contents of PC, protein content and viscosity of respiratory tract fluid of rabbits were also investigated. In respiratory tract fluid, lung washings and mucin-like substance of rabbits, saturated FA, especially C16:0, were predominant components of PC; while in sputum and lung tissue of rabbits and respiratory tract fluid of hens, unsaturated FA, especially C18:1 and C18:2, were more predominant components in comparison with those in the above specimens. Ambroxol significantly increased the contents of C16:0, saturated FA and total FA of PC, and it also increased protein content with an increase in the viscosity of respiratory tract fluid. These results suggest that in the respiratory tract fluid of rabbits, PCs are pulmonary surfactants, and the increasing secretion of pulmonary surfactant is likely to be involved in the expectorant action of ambroxol.

Ambroxol↗

PubMed1997

Antibiotic prophylaxis of lower respiratory tract contamination in horses confined with head elevation for 24 or 48 hours.

OBJECTIVE: To evaluate the administration of procaine penicillin prior to or during confinement with head elevation as a means of reducing the associated accumulation of inflammatory lower respiratory tract secretions and increased numbers of bacteria within the lower respiratory tract of confined horses. DESIGN AND PROCEDURE: Two experiments were conducted to evaluate the efficacy of different dose rates and dosing frequencies. In experiment A a single low dose (15,000 IU/kg) of procaine penicillin was administered to four horses immediately prior to confinement with head elevation for 48 hours. The systemic leucocyte response, gross and cytologic characteristics of transtracheal aspirate and bacterial numbers in lower respiratory tract samples were compared with corresponding samples from two horses confined with heads elevated but not given penicillin. The efficacy of higher dose rates (20,000 IU/kg and 40,000 IU/kg) given before and during confinement with heads elevated for 24 hours was evaluated in experiment B. RESULTS: Treatment with procaine penicillin had no effect on the systemic leucocyte response or on the accumulation of inflammatory lower respiratory tract secretions at any of the dosing schedules evaluated. The number of bacteria isolated from trans-tracheal samples was reduced at 12 hours for treated horses in experiment A and at 24 hours for experiment B. beta-haemolytic Streptococcus spp were not isolated from treated horses in either experiment. Bacterial species isolated from treated horses were predominantly Pasteurella and/or Actinobacillus spp, however, members of the family Enterobacteriaceae and a Staphylococcus sp were isolated from treated horses. One treated horse in experiment A developed clinically apparent pulmonary disease. CONCLUSIONS: The prophylactic administration of penicillin before or during confinement did not reliably reduce bacterial numbers or prevent the accumulation of purulent lower respiratory tract secretions in horses confined with their heads elevated. Numbers of beta-haemolytic Streptococcus spp were reduced following treatment, suggesting that the repeated administration of procaine penicillin may have some merit as part of a strategy to prevent transport-associated respiratory disease. However, methods directed at minimising the duration of confinement with head elevation, augmentation of the clearance of accumulated secretions and prompt identification of animals in which airway inflammation has extended to the pulmonary parenchyma remain the best ways of minimising transport-associated respiratory disease.

Actinobacillus↗

PubMed1986

A theoretical model of localized heat and water vapor transport in the human respiratory tract.

A steady-state, one-dimensional theoretical model of human respiratory heat and water vapor transport is developed. Local mass transfer coefficients measured in a cast replica of the upper respiratory tract are incorporated into the model along with heat transfer coefficients determined from the Chilton-Colburn analogy and from data in the literature. The model agrees well with reported experimental measurements and predicts that the two most important parameters of the human air-conditioning process are: the blood temperature distribution along the airway walls, and the total cross-sectional area and perimeter of the nasal cavity. The model also shows that the larynx and pharynx can actually gain water over a respiratory cycle and are the regions of the respiratory tract most subject to drying. With slight modification, the model can be used to investigate respiratory heat and water vapor transport in high stress environments, pollutant gas uptake in the respiratory tract, and the connection between respiratory air-conditioning and the function of the mucociliary escalator.

Body Temperature Regulation↗

PubMed1995

Infection with Chlamydia pneumoniae in infants and children with acute lower respiratory tract disease.

The role of Chlamydia pneumoniae in the etiology of acute lower respiratory tract infections in infants and children is little understood. We studied the prevalence of C. pneumoniae infection in hospitalized infants and children with acute lower respiratory tract disease by cell culture, polymerase chain reaction (PCR), enzyme immunoassay and serology. Of 290 patients with a mean age of 3.7 years, only 3 (1%) were identified to be infected with C. pneumoniae. One child was positive in the cell culture as well as the PCR assay. Another infant was PCR-positive only and serologic evidence of infection was observed in a culture- and PCR-negative child. Chlamydia trachomatis was not detected in any patient specimen by either culture or PCR. Results of this study indicate that C. pneumoniae plays a minor role in the etiology of respiratory tract infections in infants and young children.

Acute Disease↗

PubMed2002

Evaluation of the sensory irritation test (Alarie test) for the assessment of respiratory tract irritation.

Within the framework of risk assessment of existing substances in the EC the irritating properties on the respiratory tract should be considered. Since no standardized test is available it was studied whether the Alarie test could be used for this purpose, as proposed by the Technical Guidance Document for new and existing substances. The available literature on respiratory tract irritation, seen as a local inflammatory response and/or tissue damage, after single and repeated (few-day) exposure was evaluated and compared with data on sensory irritation. No relation was found between the sensory irritation potential (as measured by the Alarie test) and local tissue damage (histopathological changes) in the respiratory tract after single or repeated exposure. It was concluded that the Alarie test is inappropriate to evaluate respiratory tract irritation. In addition, the available data do not support a quantitative potency ranking for man based on the RD50 obtained with experimental animals.

Administration, Inhalation↗

PubMed1987

The effect of beta-carotene on BP-induced respiratory tract tumors in hamsters.

The modifying effect of beta-carotene on benzo[a]pyrene (BP)-induced tumors of the respiratory tract was investigated in Syrian hamsters. Groups of hamsters were fed a semisynthetic diet supplemented with either no or 56 mg/kg beta-carotene. Respiratory tract tumors were induced by intratracheal instillation of BP attached to ferric oxide. The beta-carotene and vitamin A contents of the liver were increased in the high beta-carotene group, but the serum beta-carotene levels were very low when compared with those commonly observed in humans. beta-Carotene supplementation did not affect the tumor response of the respiratory tract. Neither the incidence and severity of preneoplastic changes were influenced. However, there was a statistically significant inverse relationship between serum retinol content and the presence of respiratory tract tumors in survivors, regardless of the dietary treatment.

Animals↗

PubMed1999

[Analysis of clinical characteristics and drug sensitivity tests of lower respiratory tract infection by Xanthomonas maltophilia].

OBJECTIVE: To analyse the clinical characteristics of lower respiratory tract infection caused by Xanthomonas maltophilia and to investigate the antibiotic sensitivity of Xanthomonas maltophilia strains. METHODS: Retrospective study of the clinical data of 54 cases with lower respiratory tract infection by Xanthomonas maltophilia, including risk factors of morbidity, clinical symptoms and signs, X-ray findings, blood routine test, treatment and prognosis. Drug sensitivity against strains of Xanthomonas maltophilia by K-B method was studied. RESULTS: There were 39 males and 15 females, the mean age being 51 +/- 17 years. 87% of the cases had underlying diseases, most of which were COPD complicated by respiratory failure. 57% of the cases were immunocompromised. 39% of the cases were in ICU or CCU. 54% of the cases accepted invasive treatments, and 93% of the cases were given broad-spectrum antibiotics. Clinical manifestations include chill (72%), fever (80%), cough (94%) and expectoration (91%). The chest X-ray revealed infiltration in lower lobes of both lungs. 16 cases had consolidations, and 11 cases were complicated with pleural effusions. The drug sensitivity test in vitro showed that these strains were multiresistant to commonly used antibiotics, and drugs whose sensitive rate were over 50% included SMZco, ceftazidine, and timentin. CONCLUSIONS: The lower respiratory tract infections caused by Xanthomonas maltophilia develop at patients with various underlying diseases, especially in the immunocompromised patients. Risk factors of morbidity were: patients in ICU or CCU, acceptance of invasive treatment and inappropriate use of broad-spectrum antibiotics. Clinical manifestations include severely toxic symptoms and some cases had pulmonary consolidations and pleural effusions.

Adolescent↗

PubMed1992

[Effects of respiratory tract infections and antibiotic therapy on NADPH oxidase activity].

The superoxide generation of neutrophil NADPH oxidase was investigated in healthy subjects, patients with respiratory tract infections, and patients receiving effective antibiotic therapy. In adults, oxidase activity significantly increased during respiratory tract infections and decreased after treatment with effective antibiotics. In the elderly, no significant increase in oxidase activity was observed during respiratory tract infections, while the activity significantly decreased after therapy. Increases in white blood cell counts, neutrophil counts and C-reactive protein values in the elderly during respiratory tract infections were less marked than those in adults. These abnormalities in both adults and the elderly were restored to within normal limits after antibiotic therapy. In in vitro experiments, antibiotics, such as imipenem, ceftazidime and cefoperazone, at each therapeutic dose did not inhibit the superoxide generation of NADPH oxidase. These results suggest that in the elderly, defense activity against infections may be suppressed, and that these antibiotics may normalize neutrophil NADPH oxidase activity as a result of their bactericidal action and a possible biological action to normalize the peri-neutrophil environment of the body.

Adult↗

PubMed1997

Noncoordinated expression of alpha-, beta-, and gamma-subunit mRNAs of epithelial Na+ channel along rat respiratory tract.

Na+ reabsorption from the epithelial surface of the respiratory tract plays a fundamental role in respiratory physiology. As in the epithelia of the renal collecting tubule and distal colon, Na+ enters across the luminal surface of respiratory epithelial cells via a recently cloned amiloride-sensitive multisubunit (alpha, beta, gamma) epithelial Na+ channel. We have examined the cellular expression at the mRNA level of the alpha-, beta-, and gamma-subunits of rat epithelial Na+ channel (rENaC) in the rat lung and upper airway epithelial cells using in situ hybridization. A large prevalence of alpha- and gamma-rENaC subunit expression (over beta) was found in tracheal epithelium, in a subpopulation of alveolar cells, presumably type II pneumocytes, and in nasal and tracheal gland acini. In contrast, equivalent levels of expression of all three subunits were detected in bronchiolar epithelium and in rat nasal gland ducts. This diversity of expression may reflect cell-specific functions of the amiloride-sensitive Na+ channel along the respiratory tract.

Animals↗

PubMed1997

Clarithromycin. A review of its efficacy in the treatment of respiratory tract infections in immunocompetent patients.

Clarithromycin is a broad spectrum macrolide antibacterial agent active in vitro and effective in vivo against the major pathogens responsible for respiratory tract infections in immunocompetent patients. It is highly active in vitro against pathogens causing atypical pneumonia (Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp.) and has similar activity to other macrolides against Staphylococcus aureus. Streptococcus pyogenes, Moraxella catarrhalis and Streptococcus pneumoniae. Haemophilus influenzae is susceptible or intermediately susceptible to clarithromycin alone, but activity is enhanced when the parent drug and metabolite are combined in vitro. Absorption of clarithromycin is unaffected by food. More than half of an oral dose is systemically available as the parent drug and the active 14-hydroxy metabolite. Pharmacokinetics are nonlinear, with plasma concentrations increasing in more than proportion to the dosage. First-pass metabolism results in the rapid appearance of the active metabolite 14-hydroxy-clarithromycin in plasma. Clarithromycin and its active metabolite are found in greater concentrations in the tissues and fluids of the respiratory tract than in plasma. Dosage adjustments are required for patients with severe renal failure, but not for elderly patients or those with hepatic impairment. Drug interactions related to the cytochrome P450 system may occur with clarithromycin use. In addition to the standard immediate-release formulation for administration twice daily, a modified-release formulation of clarithromycin is now available for use once daily. In dosages of 500 to 1000 mg/day for 5 to 14 days, clarithromycin was as effective in the treatment of community-acquired upper and lower respiratory tract infections in hospital and community settings as beta-lactam agents (with or without a beta-lactamase inhibitor), cephalosporins and most other macrolides. Clarithromycin was similar in efficacy to azithromycin in comparative studies and is as effective as and better tolerated than erythromycin. Adverse events are primarily gastrointestinal in nature, but result in fewer withdrawals from therapy than are seen with erythromycin. Clarithromycin provides similar clinical and bacteriological efficacy to that seen with beta-lactam agents, cephalosporins and other macrolides. It offers a cost-saving alternative to intravenous erythromycin use in US hospitals and is available in both once-daily and twice-daily formulations. The spectrum of activity of clarithromycin against common and emerging respiratory tract pathogens may make it suitable for use in the community as empirical therapy of respiratory tract infections in both children and adults.

Adult↗

PubMed2003

Infectious aetiologies in elderly patients hospitalised with non-pneumonic lower respiratory tract infection.

OBJECTIVE: to identify the infectious aetiologies of non-pneumonic lower respiratory tract infections in hospitalised elderly patients, and to characterise the patients in terms of demographic, clinical and therapeutic variables. DESIGN: a prospective, non-interventional, purely serologically based diagnostic study. SETTING: a tertiary university hospital in southern Israel. SUBJECTS: 133 elderly patients hospitalised for non-pneumonic lower respiratory tract infections. METHODS: paired sera were obtained for each of the hospitalisations and were tested using immunofluorescence or enzyme immunoassay methods to identify 13 different pathogens. Only significant changes in antibody titers or levels between the paired sera were considered diagnostic. RESULTS: at least one infectious aetiology was identified in 77 patients (58%). At least one of seven viral aetiologies was identified in 52 patients (39%). A bacterial aetiology was identified in 27 patients (20%) including Streptococcus pneumoniae in 24 (18%). An atypical bacterium was found in 27 patients (20%) including Mycoplasma pneumoniae in 15 (11%) and Legionella spp. in nine (7%). More than one aetiology was found in 23 patients (17%). One hundred and twenty nine patients (96%) suffered from serious chronic co-morbidity. One hundred and twenty one patients received antibiotics during their hospitalisation, 106 (80%) with a beta-lactam and 42 (31%) with another antibiotic. CONCLUSIONS: non-pneumonic lower respiratory tract infection is caused in hospitalised elderly patients by a broad spectrum of aetiological agents, primarily respiratory viruses with a significant, though lesser, prevalence of classical and atypical bacteria. Despite this distribution of aetiologies, most patients are treated with beta-lactam antibiotics. The indication for antibiotic therapy in these patients and the choice of antibiotic preparation should be addressed in further studies.

Aged↗

PubMed1986

An investigation into the effect of the IgG antibody system on the susceptibility of IgA-deficient patients to respiratory tract infections.

Serum IgG subclass concentrations and IgG-tetanus toxoid antibody (IgG-TTab) responses were measured in IgA-deficient patients with severe respiratory tract infections (n = 11), mild respiratory tract infections (n = 5) or no increased susceptibility to respiratory tract infections (n = 15). The severe infection group had lower IgG2 concentrations than the patients without infections (P less than 0.02) and was the only group with IgG2-deficient patients (36%). The number of sera in which IgG4 was not detected was higher in patients with severe infections than in both normal controls (45% vs 10%, P less than 0.01) and the other IgA-deficient patients (45% vs 20%), in part explained by a strong association with IgG2 deficiency. Subnormal IgG-TTab responses were demonstrated in 45% of patients with severe infections but in only one patient from each of the other two groups. Five patients with IgG2 deficiency and/or subnormal IgG-TTab responses were treated with gammaglobulin and apparently improved. There was a high serum concentration of IgG1 in 35% and IgG3 in 19% of the 31 patients, predominantly in those without severe infections. Thus a proportion of IgA-deficient patients have additional defects of IgG; IgG1 and IgG3 antibody responses may compensate for the IgA deficiency in asymptomatic patients.

Adolescent↗

PubMed1985

Economic costs of respiratory tract infections in the United States.

To evaluate one aspect of the impact of respiratory tract infections in the United States, national survey data were used to estimate direct and indirect economic costs. Overall, upper and lower respiratory tract infections are estimated to be responsible for approximately $15 billion in direct treatment costs. Physician charges account for about one half and hospital care accounts for approximately one quarter of these costs. An estimated 1.25 million patients are hospitalized yearly for community-acquired respiratory tract infections, and charges for their care are projected to exceed $4 billion. Almost 300 thousand patients acquire nosocomial respiratory infections yearly, and charges for treating these infections are approximately $470 million. Although costs associated with hospital care are substantial, approximately $10 billion (67 percent of the total estimated cost of these infections) results from treatment of patients in ambulatory settings. It is not possible to calculate the full magnitude of the indirect costs of respiratory infections, but losses in income of employed persons who miss work because of infection are calculated to be more than $9 billion per year.

Ambulatory Care↗

PubMed1979

Amyloid in localised deposits and plasmacytomas of the respiratory tract.

Clinical and histological features of 25 cases with amyloid deposits in the respiratory tract are described. The false cord is the commonest single site of such "primary" amyloid involvement. Evidence of extensive involvement and replacement of seromucinous glands by amyloid was seen in each case. Fourteen cases of plasmacytoma with "secondary" amyloid deposits are also described. The nose and nasopharynx were principally involved as with respiratory tract plasmacytomas in general but a similar association of the amyloid with seromucinous glands was also seen. Electron microscopy showed early involvement of the basal lamina of the duct of a seromucinous gland by amyloid in one case. Possible reasons for the association of amyloid precursors in respiratory tract amyloid with seromucinous glands are given.

Adult↗

PubMedDate not supplied

Leptospirotic etiology in pulmonary and upper respiratory tract pathology.

A number of 3,200 febrile patients who presented upon admission to hospital primary pulmonary or upper respiratory tract impairment either as single forms of manifestation or associated to other syndromes were tested. The cases were screened by the rapid slide agglutination reaction with heat inactivated Patoc antigen and leptospirotic etiology was confirmed by the ultramicroscopic agglutination reaction with 18 live circulating pathogenic antigens. 64 leptospirosis cases with pulmonary impairment were confirmed and in 52 cases the upper respiratory tract was involved. Particular aspects of leptospirosis with pulmonary impairment: 71.8% of cases had a clinical diagnosis of interstitial pneumonia; 89% of cases presented important chest x-ray modifications; in an approximately equal number of cases the pulmonary involvement was the single manifestation or was associated with other syndromes; icterohaemorrhagiae, wolffi and pomona were the frequently encountered infecting serotypes. Particular aspects for leptospirosis involving the upper respiratory tract: 84.6% of cases had a clinical diagnosis of acute rhino-pharyngotracheitis; in 86.5% of cases the upper respiratory tract impairment was the single feature; the infecting serotypes were in decreasing order of frequency as follows: icterohaemorrhagiae, pomona, wolffi, canicola, grippotyphosa.

Adolescent↗