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Clinical and bacteriological efficacy in treatment of acute exacerbations of chronic bronchitis with cefditoren-pivoxil versus cefuroxime-axetil.

A randomized, double-blind, double-dummy trial was performed comparing 200 mg of cefditoren-pivoxil twice daily for 5 days versus standard cefuroxime-axetil treatment (250 mg twice daily for 10 days) of Anthonisen type I or II acute exacerbations of chronic bronchitis. The modified intention-to-treat population included 541 patients. Patients were assessed during therapy, at the end of therapy (visit 3; primary evaluation time point), and at follow-up. Clinical success was obtained in 79.9% of the 264 patients included in the cefditoren-pivoxil group and in 82.7% of the 277 patients in the cefuroxime-axetil group (treatment difference, 95% confidence interval [CI]: -2.8, -9.7 to 3.6%). Treatment clinical effects were more clearly seen in sputum signs (decreasing volume and purulence from approximately 80% to approximately 10% of the patients). At the end of treatment, exploratory analysis of the per-pathogen bacteriological response showed 72.8% (of 103 isolates) in the cefditoren-pivoxil arm versus 67.0% (of 94 isolates) in the cefuroxime-axetil group (treatment difference; 95% CI: 5.8, -7.0 to 18.6%). Globally, the per-pathogen bacteriological response correlated well with clinical success: 83.5% of 164 baseline isolates from patients with a clinical success were eradicated or presumably eradicated, in contrast to only 3% of 33 isolates from patients with a clinical failure. Clinical success in patients infected with Haemophilus influenzae, the most frequent isolate, was 84% (of 50) and 82.5% (of 40) (treatment difference; 95% CI: 1.5, -14 to 17%) in the cefditoren-pivoxil versus the cefuroxime-axetil group. Although this study does not prove that either drug is better than a placebo, cefditoren-pivoxil and the standard 10-day cefuroxime-axetil course had similar point estimates of success in acute exacerbations of chronic bronchitis.

Acute Disease↗

Infectious bronchitis and mixed infections of Mycoplasma synoviae and Escherichia coli in gnotobiotic chickens. I. Synergistic role in the airsacculitis syndrome.

The synergistic role of infectious bronchitis virus (IBV) and mixed infections of Mycoplasma synoviae (MS) and Escherichia coli (EC) in the airsacculitis syndrome was evaluated in gnotobiotic chickens. Relative air sac lesion score indexes, in descending order of severity, from various combinations of organisms were: 9.5-IBV, MS, EC; 6.8-IBV, EC; 4.5-IBV, MS; 2.7-IBV; and 0.5-MS, EC. Infectious bronchitis virus caused a mild fibrinous inflammation. M. synoviae combined with IBV increased heterophilic and follicular lymphoid infiltration and mortality. E. coli combined with IBV increased exudation and prolonged airsacculitis. Concentrations of fibrinogen, gamma globulin, and total plasma proteins were elevated significantly by combined infections of IBV, MS, and EC (P < 0.01).

Air Sacs↗

Oligonucleotide fingerprinting of ribonucleic acids of infectious bronchitis virus strains.

A total of 11 distinct oligonucleotide fingerprints were obtained in studies of the ribonucleic acids of 13 isolates of infectious bronchitis virus. Different serotypes had distinct fingerprints, but so did varieties within a serotype, allowing a greater degree of strain differentiation than was previously possible. Some conclusions can be drawn from the fingerprints concerning theories of origin and spread of infectious bronchitis virus.

Coronaviridae↗

Differences in adhesion of Pseudomonas aeruginosa to mucin glycopeptides from sputa of patients with cystic fibrosis and chronic bronchitis.

Pseudomonas aeruginosa is the most prominent colonizer of the respiratory tract of patients with cystic fibrosis, but it is not known why this occurs. P. aeruginosa adheres to mucins from normal individuals, but mucins from cystic fibrosis patients have not been studied. To compare adhesion to mucins from cystic fibrosis with other mucins, we prepared highly glycosylated mucin glycopeptides from cystic fibrosis and chronic bronchitis patients by ion-exchange and gel-filtration chromatography and measured the adhesion of P. aeruginosa 1244 to these glycopeptides. We found (i) that the most mucinlike glycopeptides from P. aeruginosa-infected cystic fibrosis sputa showed less bacterial adhesion than did the corresponding bronchitis samples, (ii) that the most adhesive activity in cystic fibrosis samples came from a fraction that contains O and N glycopeptides and may be in part a degradation product of P. aeruginosa infection, and (iii) that highly glycosylated glycopeptides of the most acidic species (sialylated and sulfated) showed no adhesion at all. A single cystic fibrosis sample not infected by P. aeruginosa showed better binding in the adhesion-positive fractions than did the infected sputa. These studies suggest that cystic fibrosis mucins may be altered after infection is established, resulting in less binding to some fragments. However, since the clinical picture shows heavy mucus colonization, other receptors, such as cellular glycolipids which have been shed into mucus, may be contributing to this colonization.

Bacterial Adhesion↗

Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus.

Avian coronavirus infectious bronchitis virus (IBV) is the causative agent of chicken infectious bronchitis, an acute, highly contagious viral respiratory disease. Replication of IBV in Vero cells causes extensive cytopathic effects (CPE), leading to destruction of the entire monolayer and the death of infected cells. In this study, we investigated the cell death processes during acute IBV infection and the underlying mechanisms. The results show that both necrosis and apoptosis may contribute to the death of infected cells in lytic IBV infection. Caspase-dependent apoptosis, as characterized by chromosomal condensation, DNA fragmentation, caspase-3 activation, and poly(ADP-ribose) polymerase degradation, was detected in IBV-infected Vero cells. Addition of the general caspase inhibitor z-VAD-FMK to the culture media showed inhibition of the hallmarks of apoptosis and increase of the release of virus to the culture media at 16 h postinfection. However, neither the necrotic process nor the productive replication of IBV in Vero cells was severely affected by the inhibition of apoptosis. Screening of 11 IBV-encoded proteins suggested that a 58-kDa mature cleavage product could induce apoptotic changes in cells transiently expressing the protein. This study adds one more example to the growing list of animal viruses that induce apoptosis during their replication cycles.

Amino Acid Chloromethyl Ketones↗

Effect of salbutamol in infants with wheezy bronchitis.

Using the technique of whole body plethysmography, lung mechanics were measured in a group of infants with wheezy bronchitis. Compared with a group of normal infants previously studied, airway resistance and thoracic gas volume were found to be raised. Nebulized salbutamol was then administered and measurements were repeated when it was found that there was no objective improvement. It is concluded that salbutamol may not be an effective form of treatment of wheezy bronchitis in young infants and the reasons for this are discussed.

Airway Resistance↗

Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis.

Rutter, N., Milner, A. D., and Hiller, E. J. (1975). Archives of Disease in Childhood, 50, 719. Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis. Respiratory resistance was measured using a forced oscillation technique in 16 infants and young children with bronchiolitis and wheezy bronchitis. Measurements were made before and after administration of nebulized salbutamol or isoprenaline. No significant change in resistance was found.

Airway Resistance↗

Alpha and beta adrenergic stimulants in bronchiolitis and wheezy bronchitis in children under 18 months of age.

Total respiratory resistance was measured before and after nebulised phenylephrine in 5 babies (age range 7 to 17 months) with wheezy bronchitis, and in 2 babies (aged 2 and 6 months) with bronchiolitis. None showed a change in resistance after treatment. Total respiratory resistance was measured before and after nebulised adrenaline in another 14 babies (age range 4 to 13 months) with bronchiolitis. No fall in resistance was noted in any baby after treatment whether or not it was given by a conventional or an ultrasonic nebuliser. We conclude that alpha- and beta-adrenergic stimulants are ineffective in bronchiolitis and wheezy bronchitis in children under 18 months of age.

Aerosols↗

Role of viruses and bacteria in acute wheezy bronchitis in childhood: a study of sputum.

Sputum, nasal swabs, and throat swabs were obtained from 22 children aged between 5 and 15 years during 72 attacks of wheezy bronchitis. A virus, most commonly a rhinovirus, was isolated in 49% of all episodes and in 64% of 22 severe episodes requiring treatment with corticosteroids; the isolation rate was higher early in the illness than later. Virus was recovered more often from sputum than from the nose or throat, suggesting that viral replication occurs freely in the lower respiratory tract: the cytological findings in sputum were compatible with an inflammatory response to viral infection. Pathogenic bacteria appeared to play a minor role compared with viruses, and routine antibiotic treatment was probably of little value in moost cases. The significance of the results is discussed in relation to the pathogenesis of childhood wheezy bronchitis.

Acute Disease↗

Chronic bronchitis: method of cigarette smoking.

Male volunteers for mass radiography examination, aged 40 or more, were questioned about their sputum production, smoking habits, and, when applicable, their method of smoking cigarettes.Of 5,438 cigarette smokers 460 (8.4%) smoked their cigarettes without removing the cigarette from the mouth between puffs ("drooping" cigarette smokers) whereas the rest smoked in the normal manner.Persons who admitted to producing sputum from their chests on most days of the year or on most days for at least three months of the year for a minimum of two years were classified as chronic bronchitics in the absence of other causative disease.The rate of chronic bronchitis among the "drooping" cigarette smokers (41.5%) was considerably greater than that among those smoking cigarettes in the normal manner (33.6%). The same pattern was maintained when age and cigarette consumption were standardized, though "drooping" cigarette smokers had a slight bias towards plain as distinct from filter cigarettes and towards a lower social class this was not sufficient to account for the excess of chronic bronchitis among those using this method of smoking.

Adult↗

Comparison of aerosol ipratropium bromide and salbutamol in chronic bronchitis and asthma.

The effects of inhaling 200 mu g of salbutamol were compared with those of inhaling 40 mu g of ipratropium bromide singly and in combination with salbutamol in eight patients with bronchitis and eight asthmatic patients in a double-blind controlled trial. Changes in airways resistance were assessed by measuring the forced expiratory volume in 1 second and specific airways conductance. Both drugs were significantly better in relieving airways obstruction than placebo. Salbutamol was significantly more effective than ipratropium bromide in patients with asthma, but in the patients with bronchitis there was no significant difference between salbutamol and ipratropium bromide. The combination of the two drugs produced a slightly greater and longer response than either drug alone but this was not significant.

Aerosols↗

Twelve-minute walking test for assessing disability in chronic bronchitis.

The distance covered in 12 minutes' walking was used to test exercise tolerance in chronic bronchitis. The distance covered bore a poor relation to the forced expiratory volume in 1 second but a significant relation to the forced vital capacity and the maximum oxygen consumption and ventilation on a bicycle ergometer. The test may be a simple practical guide to everyday disability in chronic bronchitis.

Adult↗

Effect of nitrazepam in chronic obstructive bronchitis.

The effect of nitrazepam on ventilatory capacity and arterial blood gas tensions was studied in a double-blind controlled crossover trial in six patients with chronic obstructive bronchitis in ventilatory failure (raised Paco(2)). Nitrazepam produced a fall in ventilatory capacity and worsening of the ventilatory failure. In the sixth patient, while on the active drug, the Pao(2) fell from 48 to 35 mm Hg while the Paco(2) tension rose from 59.5 to 68 mm Hg. It is suggested that nitrazepam is contraindicated in patients with severe chronic obstructive bronchitis.

Aged↗

Cigarette smoker's bronchitis: the effect of relighting.

Male volunteers for mass radiography examination aged 40 or more were questioned about their sputum production, smoking habits, and, when applicable, their method of smoking cigarettes.Of 5,438 cigarette smokers 1,051 (19%) claimed that when smoking a cigarette they usually extinguished it at some stage and later relit it to smoke again. Anyone who admitted to producing sputum from his chest on most days of the year or on most days for a minimum of three months of the year for at least the last two years was classed, in the absence of other causative disease, as a chronic bronchitic. Such chronic bronchitics totalled 1,864 (34%).The rate of chronic bronchitis among relighters (39.7%) was higher than the rate (32.9%) among the remaining cigarette smokers. The difference was of high statistical significance (P<0.001), and the same pattern was maintained when age and consumption were standardized. After allowing for a trend towards lower social class and a preference for plain as opposed to filter cigarettes the rate of chronic bronchitis among relighters was about 15% greater than that of the remaining cigarette smokers.

Behavior↗

Physiotherapy and intermittent positive-pressure ventilation of chronic bronchitis.

Patients aged over 45 admitted to hospital with exacerbations of chronic bronchitis alone or in association with cor pulmonale, pneumonia, or respiratory failure were placed in one of three groups (men with hypoxia, men without hypoxia, and women). Patients within these groups were then randomly allocated to receive either standard drug treatment alone or standard drug treatment plus intermittent positive-pressure ventilation (IPPV). No significant differences occurred between the controls and patients receiving physiotherapy and IPPV in any group. We conclude that when a patient with chronic bronchitis and respiratory failure is deteriorating emphasis should be on correct diagnosis, fluid electrolyte balance, and nutrition together with oxygen treatment when necessary, rather than on additional physiotherapy.

Aged↗

Effects of oral and inhaled salbutamol and oral pirbuterol on right and left ventricular function in chronic bronchitis.

In many patients with chronic bronchitis and emphysema right and left ventricular ejection fractions (RVEF and LVEF) are reduced. A study was conducted using multiple gated equilibrium radionuclide ventriculography to compare the effects of oral salbutamol 4 mg and pirbuterol 15 mg on cardiac function in 12 patients with chronic bronchitis (forced expiratory volume in one second 0.86 (SEM 0.12) 1; arterial oxygen pressure 8.2 (SEM 0.5) kPa (61.7 (SEM 3.8) mm Hg)). Different doses of nebulised salbutamol (500 microgram and 5 mg) were also compared in nine of the patients. Both oral salbutamol and oral pirbuterol produced significant increases in RVEF and LVEF at 60 and 90 minutes after drug ingestion (p less than 0.01 in each case). There were no significant differences between salbutamol and pirbuterol in their effects on RVEF and LVEF. Inhaled salbutamol at doses commonly prescribed had no significant effect on RVEF and LVEF after 20 and 60 minutes. Salbutamol and pirbuterol given by mouth have similar actions on RVEF and LVEF. Further studies are necessary to assess the effects of long term B2 agonists in this group of patients.

Administration, Intranasal↗

Viral antibody levels and clinical status in acute exacerbations of chronic bronchitis: a controlled prospective study.

A controlled prospective study was made of a group of patients with chronic bronchitis, in which serum antibodies against a group of viruses and Mycoplasma pneumoniae were estimated at regular intervals. Sixteen significant rises in antibody titre were shown, of which eight were associated with clinical acute exacerbations of bronchitis. In individual patients no correlation was found between the number of acute exacerbations or the aetiological agent and persistent change in ventilatory function as expressed by the F.E.V.(0.75).This study was compared with the results of a previous parallel investigation of the same patients done to study the significance of rhinovirus infections. In the present investigation 12% of the acute exacerbations were associated with the 11 agents tested compared with 14% associated with rhinoviruses in the earlier work.

Adenoviridae↗

Single-blind comparative trial of trimethoprim-sulphamethoxazole and ampicillin in the treatment of exacerbations of chronic bronchitis.

Fifty patients with exacerbations of chronic bronchitis were treated with either a combination of trimethoprim 320 mg. and sulphamethoxazole 1,600 mg. a day or ampicillin 2 g. a day. The trial, carried out as a single-blind procedure, showed that the combination was more effective as judged by clinical response and reduction in sputum volume and purulence, with eradication of pathogenic organisms. No appreciable side-effects were encountered with either treatment, and it is suggested that the trimethoprim-sulphamethoxazole combination may be a safe and useful drug in the treatment of chronic bronchitis.

Ampicillin↗