Chronic Bronchial Infection Research Articles

Mucoviscidose

Cystic fibrosis (CF) is the most frequent severe genetic disease in Caucasian populations. The modified gene codes for the CFTR (cystic fibrosis transmembrane conductance regulator) protein, a chloride channel which is expressed in many organs. Clinical manifestations begin early in life and are dominated by the respiratory disease which conditions morbidity and mortality. The clinical symptoms are secondary to bronchiectasis and chronic bronchial infection with Staphylococcus aureus and Haemophilus influenzae, then with Pseudomonas aeruginosa, leading to acute exacerbations and finally to chronic respiratory insufficiency. The digestive tract symptoms are the second more frequent symptoms, mainly due to exocrine pancreatic insufficiency, but intestinal or liver disease is possible. Rhino-sinusitis, diabetes, osteoporosis and bilateral absence of the vas deferens are other manifestations of CF. The diagnosis is based on the sweat test and genotyping. Late diagnosis in adulthood is possible. Neonatal screening has been generalised in France in 2002. Care for CF patients is given in paediatric and adult CF centres by a multidisciplinary team who works with a network of caregivers in the hospital and at home. The treatment is based on chest physiotherapy and antibiotics in order to fight bronchial infection, and on digestive and nutritional measures. Lung transplantation is indicated in case of severe respiratory insufficiency. The improvement in the care of CF leads to improvement in survival (median survival above 30 years) and to an increase in the number of adult patients (1/3 of patients) requiring a specific follow-up.

Atypical sinusitis in adults must lead to looking for cystic fibrosis and primary ciliary dyskinesia.

HYPOTHESES/OBJECTIVES:: In adults, purulent pansinusitis or nasal polyposis starting early in life or that is permanently infected or associated either with chronic bronchial infection, infertility, or situs inversus are uncommon. In these atypical cases of chronic sinusitis (ACS), a primary dysfunction of the mucociliary clearance can be suspected. Adult patients with ACS were therefore investigated to detect primary ciliary dyskinesia (PCD) or cystic fibrosis (CF). Open, prospective study. Forty-two patients with ACS were investigated with ciliary beat frequency and ultrastructure analysis in nasal cells and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis in blood leukocytes. The diagnosis of PCD was confirmed in seven (17%) patients. At least one CFTR gene mutation was detected in 16 (38%) patients. The diagnosis of CF was suggested in three (7%) compound heterozygous patients. Another 13 (31%) patients were heterozygous for a CFTR gene mutation or a complex allele. Comparison of clinical features of ACS showed that only a family history of chronic sinusitis (P <.01) or chronic bronchitis (P <.02) and the presence of diffuse bronchiectasis (P <.0001) or serous otitis media (P <.0001) were significantly more frequent in PCD patients than in patients carrying CFTR gene mutations or those without PCD or CFTR gene mutations. ACS should be considered a remarkable entity in which congenital abnormalities of epithelial cells are frequently detected (55% of patients). The higher frequency of mutations in ACS patients compared with the general population suggests that heterozygoty for CFTR gene mutation could be a sinusitis-causing status.

Dyskinetic cilia and Kartagener's syndrome. Bronchiectasis with a twist.

Kartagener’s published description of the syndrome of sinusitis, bronchiectasis, and situs inversus achieved eponymous recognition for him (1), although the clinical features had apparently been described previously by Siewert (2). A familial tendency was noted in some subsequent cases, and it was concluded that the condition was probably hereditary. In 1975, Camner et al. (2) reported immotile respiratory cilia and immotile spermatozoa in two patients with Kartagener’s syndrome. They suggested that the basis for the chronic sinusitis, bronchial infections, and bronchiectasis was impaired ciliary clearance of mucus due to the immotility of the respiratory cilia. Subsequent studies have shown that a variety of ciliary morphologic defects and abnormalities are detectable by electron microscopy and are accompanied by absence of motility in the cilia (4). The term “immotile cilia syndrome” was proposed for such cases (5). As many of these patients did not have situs inversus, it was concluded that Kartagener’s syndrome is a subgroup or variant of the immotile cilia syndrome. It is now recognized that the anatomically abnormal cilia are not always immobile, although the movement, when present, is dysfunctional, dyskinetic, and ineffective. The terms “dyskinetic cilia syndrome” (DCS) and primary ciliary dyskinesia are now applied to this syndrome. The latter term is pertinent because anatomic abnormalities in the respiratory cilia may also be secondary to pre-existing destruc-

Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean ± sem) of group A [0·6 (1·5) and 13·1 (34·8)] were lower than those of group B [2·5 (2·1) and 57·9 (41·8)] ( P<0·05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV 1), P aO 2 and P aCO 2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.

Role of intracellular pathogens in respiratory tract infections

Recent epidemiologic studies have shown that in patients with acute respiratory tract infection, intracellular pathogens, and particularly Mycoplasma pneumoniae and Chlamydia pneumoniae, might be involved more frequently than was previously assumed. In addition, newer investigations, such as specific culture or polymerase chain reaction (PCR), when systematically performed in patients with asthma, chronic obstructive pulmonary disease and even cystic fibrosis, frequently detect Mycoplasma pneumoniae or Chlamydia pneumoniae in those individuals. The significance of such detection (chronic bronchial infection?) and the role that these intracellular pathogens might play in the natural history of chronic respiratory diseases remain to be evaluated.

Association between acute cerebrovascular ischemia and chronic and recurrent infection.

We performed a case-control study to investigate whether chronic or recurrent respiratory, ear-nose-throat (ENT), and dental infections are risk factors for cerebrovascular ischemia. Using a standardized questionnaire we investigated past infectious diseases in 166 consecutive patients with acute cerebrovascular ischemia and in 166 age- and sex-matched nonstroke neurological patient controls. In subgroups, we performed standardized ENT (69 patients, 66 control subjects) and dental examinations including orthopantomography (66 patients, 60 control subjects). Dental status was determined by a total dental index (TDI) that reflects caries, periapical lesions, periodontitis, and other dental lesions and by an orthopantomography index (OPGI) that was assessed blinded. Frequent (> or = 2 episodes in each of the 2 preceding years) or chronic bronchitis was associated with cerebrovascular ischemia in age-adjusted multiple logistic regression analysis (odds ratio, OR, 2.2; 95% confidence interval, CI, 1.04 to 4.6). Groups were not different in ENT examination. Patients tended to have a worse dental status (TDI: P = .070; OPGI: P = .062) and had more severe periodontitis (P = .047) and periapical lesions (P = .027) than control subjects. In age-adjusted multiple logistic regression analysis with social status and established vascular risk factors, poor dental status (TDI) was independently associated with cerebrovascular ischemia (OR, 2.6; 95% CI, 1.18 to 5.7). Recurrent or chronic bronchial infection and poor dental status, mainly resulting from chronic dental infection, may be associated with an increased risk for cerebrovascular ischemia.

Bronchiectasis and related disorders.

Bronchiectasis is defined in current medical parlance as the abnormal and permanent dilatation of one or more bronchi, and in clinical practice, the condition is often characterized by features of chronic bronchial infection. Apart from occurring as a primary lung disease, bronchiectasis is a major component of two other disease entities, cystic fibrosis and diffuse panbronchiolitis. Although the three conditions have distinctly different underlying causes, they share the similarity of a predominantly neutrophilic airways inflammation, and the persistent bronchial infection by bacteria, in particular Pseudomonas aeruginosa. Hence, new knowledge in one disease may be explored and applied in the others.

Bacteriologic diagnosis of respiratory tract infection

The use of the Gram stain for determination of the presence of bacteria in respiratory secretions is described. Success of the procedure depends on the use of fresh samples of high cellular quality. The Gram stain can be used to distinguish the presence (among other organisms) of Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis enterobacteria and Pseudomonas. This paper also discusses the use of sputum samples for bacteriologic culture and the value of bacterial counts in expectorated sputum, and describes the use of transtracheal aspiration and transthoracic aspiration puncture. Finally, it considers the optimum procedures for the testing of antibiotic susceptibility of presumptive pathogens isolated from the lower respiratory tract.

A Case of Kartagener's Syndrome Presenting as Respiratory and Right Heart Failures

Kartagener's syndrome, a congenital disease transmitted as an autosomal recessive illness with a prevalence of approximately 1:20,000 persons, is characterized by the triple association of situs inversus, bronchiectasis, and sinusitis. Affected persons have an incoordination of ciliary motility that leads to defective mucociliary transport, chronic bronchial infections. Kartagener's syndrome is a subset of the immotile cilia syndrome and therefore all patients with Kartagener's syndrome have immotile cilia with obvious ultrastructural defects in the ciliary axoneme. In the respiratory tract this inability presumably causes impaired clearance of mucus and inhaled particles and results in the chronic infections of the sinuses and bronchial trees that are characterized of the disease. The end-stage phenomenon in Kartagener's syndrome, respiratory or heart failure is a less common event and heart-lung transplantation is becoming an accepted therapy for patients with end-stage pulmonary disease in Kartagener's syndrome in many institutes. We report one case of Kartagener's syndrome in a 25-year-old young woman who was presented as respiratory and right heart failures, with review of literatures.

Cells and cytokines in chronic bronchial infection.

Cells and cytokines in chronic bronchial infection.

Nedocromil sodium in the management of chronic bronchial infection

A double–blind parallel group comparative pilot study was carried out in patients with bronchiectasis to evaluate the anti–inflammatory effect of nedocromil sodium in chronic bronchial infection. Patients were randomized to either a nedocromil sodium metered dose inhaler, 4 mg, four times daily, or placebo for 12 weeks. Clinical symptoms, lung function tests and sputum characteristics of volume, purulence, leucocyte count, neutrophil chemotactic activity and elastolytic activity were evaluated at baseline, after 4, 8 and 12 weeks of the trial. Patients were withdrawn when they had acute infective exacerbation. There were 13 evaluable patients and results were statistically analysed at 8 weeks due to the limited number of patients remaining in the study at 12 weeks. There was no significant change in any of the parameters in either active or placebo group. Hence, nedocromil sodium has not been found to contribute to the management of stable bronchiectasis in this study and larger studies are required to identify more modest effects.

Bronchial Clearance of DTPA Is Increased in Acute Asthma but Not in Chronic Asthma

To investigate bronchial permeability in asthma, we measured the bronchial clearance of 113mIn-DTPA in seven asthmatics during and after an acute attack of asthma, seven asthmatics with chronic airflow limitation, and seven asthmatics without airflow limitation but with bronchial hyperresponsiveness to methacholine. We compared these results with those from seven normal subjects, seven patients with chronic bronchitis and bronchial infection, and seven patients with emphysema. An aerosol of 113mIn-DTPA was produced with a spinning disc to ensure a predominantly bronchial deposition of inhaled particles (6.3 microns MMAD). Radioactivity over the chest was recorded with a gamma-camera for 10 min after the subject inhaled the aerosol. Central regions of interest were selected, and the logarithm of the radioactivity was plotted against time; bronchial clearance of 113mIn-DTPA was calculated as the negative slope of the regression line. Clearance was substantially higher in asthmatics during their acute attacks than in all other groups (p less than 0.0001), and it decreased toward normal levels after recovery from the acute episode. The bronchial clearance of 113mIn-DTPA in all other groups did not differ from normal. We conclude that the bronchial clearance of 113mIn-DTPA is increased in asthmatics during attacks of asthma but in the stable state is not related either to bronchial hyperresponsiveness or to airflow limitation. Our findings are best explained by an increase in permeability of the bronchial mucosa of asthmatics during acute attacks.

Effects of Human Neutrophil Elastase and Pseudomonas aeruginosa Proteinases on Human Respiratory Epithelium

It has been suggested that proteinase enzymes could play an important role in the pathogenesis of chronic bronchial infections including bronchiectasis and cystic fibrosis (CF). Because Pseudomonas aeruginosa frequently colonizes the respiratory tract in bronchiectasis and CF, we examined the in vitro effects of human neutrophil elastase (HNE) and proteinase enzymes produced by P. aeruginosa (elastase: PE; alkaline proteinase: PAP) on the ciliary beat frequency (CBF) and ultrastructure of human nasal ciliated respiratory epithelium. HNE (500 micrograms/ml) progressively reduced CBF and caused marked epithelial disruption; lower concentrations (100 and 20 micrograms/ml) also caused epithelial disruption but without slowing CBF. The effects of HNE (500 micrograms/ml) were completely abolished by adding alpha 1-antitrypsin (5 mg/ml). There was no synergy between HNE and pyocyanin, a product of P. aeruginosa which slows CBF. PE in phosphate-buffered saline also caused epithelial disruption without slowing CBF; however, PE in medium containing divalent metal ions caused CBF slowing as well as epithelial disruption at 100 micrograms/ml. PAP (500 micrograms/ml) had almost no effect on ciliated epithelium. The effects of HNE and PE on nasal and bronchial epithelium obtained from the same patient were similar. Light and transmission electron microscopy revealed that HNE and PE were cytotoxic and caused detachment of epithelial cells from neighboring cells and the basement membrane. There was cytoplasmic blebbing of the cell surface and mitochondrial damage; however, no increase of abnormalities in the ultrastructure of cilia on living cells was seen. These results support the hypothesis that HNE and PE contribute to the delayed mucociliary clearance and epithelial damage that is observed in patients with chronic bronchial infection.

Effect of bacterial products on neutrophil migration in vitro.

Chronic bronchial inflammation is associated with migration of large numbers of granulocytes into the bronchial tree. A study was designed to find out whether products of bacteria commonly isolated in chronic bronchial infection stimulate neutrophil migration in vitro. Neutrophils from healthy donors were studied by a modified Boyden chamber technique. Bacterial culture filtrates stimulated neutrophil migration over a wide dilution range and the chemotactic activity was heat stable. Culture filtrates derived from Pseudomonas aeruginosa, Streptococcus pneumoniae, and Haemophilus influenzae were significantly chemokinetic and directionally chemotactic, whereas filtrates from Staphylococcus aureus were only chemotactic. Gel filtration of S aureus and P aeruginosa culture filtrates yielded high, medium, and low molecular weight fractions showing chemotactic activity. S pneumoniae and H influenzae yielded fractions with only low molecular weight chemotactic activity. Neutrophil chemotactic responses, occurring in response to all bacterial species tested, appear to represent a defence mechanism by the host. Chemoattractant activity may, however, contribute to bronchial damage mediated by products released from continuously attracted, activated neutrophils.

Analysis of the Pathogenesis of Chronic Bronchial Infection by Bronchoalveolar and Bronchial Lavage

Analysis of the Pathogenesis of Chronic Bronchial Infection by Bronchoalveolar and Bronchial Lavage

Effect of Supernatant of Sputum from Patients with Bronchial Asthma or Chronic Bronchial Infection on Ciliary Beat Frequency

Effect of Supernatant of Sputum from Patients with Bronchial Asthma or Chronic Bronchial Infection on Ciliary Beat Frequency

Mechanism of respiratory infection due to Streptococcus pneumoniae or Haemophilus influenzae in mice

The sites of Streptococcus pneumoniae and Haemophilus influenzae infection differ in patients with respiratory infection. We investigated the in vivo mechanism of respiratory infection due to these organisms in mice, using an intranasal infection model.Growth factors such as hemin and NAD in the tracheal tissues and a growth inhibitor in the lung tissues were clearly involved in the development of H. influenzae infection. Chronic bronchial infection was caused by imparied mechanical clearance as well as by changes in the quantitative and qualitative function of neutrophilis. In S. pneumoniae infection, the decrease in the functional level of neutrophils was one of the factors in causing respiratory infection.

Antileukoprotease in Sputum during Bronchial Infections

Production of sputum and concentrations of antileukoprotease (ALP) in sputum were serially measured in hypersecreting patients with recurrent or chronic bronchial infections. Patients with stable continuous mucoid (n = 4) or purulent (n = 5) secretions had constant sputum concentrations of ALP and a calculated daily production of 1.4 and 1.9 mg of ALP per 24 hours, respectively. In patients with overt recurrent bronchial infections, production of sputum and the ALP concentration were found to be negatively correlated during treatment with antibiotics (n = 14) and during the coming (n = 5) of an exacerbation. Daily production of ALP was rather constant in these groups (2.4 and 4.8 mg, respectively, per 24 hours). While ALP was not behaving like an acute-phase protein, bronchial infection appeared to be a determinant for production of ALP; however, between individual patients with comparable severity of disease, total production of ALP varied over tenfold. Therefore, bronchial infection is not the only factor in determining production of ALP.

Conversion of benzylpenicillin to penicilloic acid in patients with chronic bronchial infections.

A colorimetric method was modified to estimate the levels of benzylpenicillin and its penicilloic acid in urine. When benzylpenicillin was given orally to healthy volunteers, both it and its penicilloic acid were detected in the urine. When benzylpenicillin was given by intramuscular injections to these volunteers, only benzylpenicillin was detected in the urine. Patients suffering from chronic bronchial infections that exhibited beta-lactamase producing gram-negative bacteria in their sputum were given benzylpenicillin intramuscularly. It was found that both benzylpenicillin and penicilloic acid were recovered from the urine of such patients.

Sputum and serum levels of amoxycillin in chronic bronchial infections

A study of II patients suffering from acute exacerbations of chronic bronchial infection, all with purulent (Mp + + +) sputum, showed that good penetration of amoxycillin into such sputum occurs. The levels of amoxycillin in sputum doubled proportionally with the oral dose, at least up to dosages of 2 g. High dosages of oral amoxycillin may therefore, be advantageous in the treatment of chronic bronchial infection. In a study of 30 chronic bronchitic patients, whose sputum varied in purulence from mucoid to purulent (Mp + + + ), the concentration of amoxycillin in sputum containing approximately 50% pus (Mp + +) was significantly higher than that in any other degree of purulence. These results indicate that amoxycillin penetrates best into sputum at an intermediate degree of purulence.