Original Article
New Strains of Bacteria and Exacerbations of Chronic Obstructive Pulmonary Disease
N Engl J Med 2002; 347:465-471August 15, 2002
- Abstract
Background
The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial. In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease. However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time. We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease.
Methods
We conducted a prospective study in which clinical information and sputum samples for culture were collected monthly and during exacerbations from 81 outpatients with chronic obstructive pulmonary disease. Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa was performed.
Results
Over a period of 56 months, the 81 patients made a total of 1975 clinic visits, 374 of which were made during exacerbations (mean, 2.1 per patient per year). On the basis of molecular typing, an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent of visits at which no new strain was isolated (P<0.001; relative risk of an exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53). Isolation of a new strain of H. influenzae, M. catarrhalis, or S. pneumoniae was associated with a significantly increased risk of an exacerbation.
Conclusions
The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease.
Media in This Article
Figure 1
Time Lines and Molecular Typing for Two Patients.Table 1
Base-Line Characteristics of 81 Patients with Chronic Obstructive Pulmonary Disease.Article Activity
- Article
Morbidity and mortality among patients with chronic obstructive pulmonary disease are related in large part to acute exacerbations, which occur one to three times per year.1-6 Our understanding of the cause and pathogenesis of these exacerbations is incomplete, and the role of bacterial pathogens is controversial.7-10
In studies performed decades ago, investigators followed patients with chronic obstructive pulmonary disease longitudinally, with periodic collection of sputum samples for culture, to determine whether there was an association between the isolation of bacterial pathogens in sputum and the occurrence of exacerbations.5,6,11 In these studies, the rate of isolation of potential bacterial pathogens from sputum samples during stable disease was identical to the rate during acute exacerbations. This finding led to the conclusion that bacterial pathogens do not cause exacerbations and that their presence in sputum is due to chronic colonization.7,12
An increased understanding of the genetic heterogeneity among strains of a bacterial species exposes a major limitation of the older cohort studies.13 At the time of these studies, it was not possible to differentiate among strains of a pathogenic bacterial species. Therefore, all strains isolated from sputum over the course of the study were regarded as identical if they belonged to the same species. This approach did not allow for the detection of changes in strains over time. More recent studies have shown that the immune response to bacterial pathogens after exacerbations of chronic obstructive pulmonary disease is characterized by considerable strain specificity, suggesting the importance of differentiation among strains of bacterial pathogens isolated over time from patients with chronic obstructive pulmonary disease.14-16
We hypothesized that the acquisition of a new strain of pathogenic bacterial species in a patient with chronic obstructive pulmonary disease who has no preexisting immunity to the strain leads to an exacerbation. To test this hypothesis, we conducted a study in which we obtained sputum samples monthly and during exacerbations in a cohort of patients with chronic obstructive pulmonary disease. Bacterial strains isolated from sputum obtained during periods of stable disease and during exacerbations were subjected to molecular typing. This report represents the results from the first 56 months of this study.
Methods
Study Design
The Human Studies Subcommittee of the Veterans Affairs Western New York Healthcare System approved the study protocol. All participants gave written informed consent. A total of 81 patients were enrolled between March 1994 and December 1998. After initial recruitment, additional patients were recruited as needed to maintain active follow-up of 50 patients. Inclusion criteria were the presence of chronic bronchitis17; the absence of asthma and bronchiectasis on the basis of a clinical assessment; an ability to comply with a schedule of monthly clinical visits; and the absence of immunosuppressive or other life-threatening disorders. The patients were seen monthly, as well as whenever they had symptoms suggestive of an exacerbation, at an outpatient clinic in the Buffalo Veterans Affairs Medical Center.
At each visit, clinical information and sputum and serum samples were obtained. The patients were questioned about the status of their chronic respiratory symptoms (dyspnea, cough, sputum production, viscosity, and purulence), and the responses were graded as 1 (at the usual level), 2 (somewhat worse than usual), or 3 (much worse than usual). A minor worsening of two or more symptoms or a major worsening of one or more symptoms prompted a clinical assessment of the cause. If the patient had fever (a temperature that exceeded 38.3°C), appeared ill, or had signs of consolidation on examination of the lungs, a chest film was obtained to rule out pneumonia. If other causes of the worsening of symptoms, such as pneumonia, upper respiratory infection, and congestive heart failure, were ruled out, the patient was considered to be having an exacerbation of chronic obstructive pulmonary disease. The determination of whether the patient had stable disease or an exacerbation was made before the results of sputum cultures were available.
Sputum Samples
The study personnel who processed the sputum samples were unaware of the clinical status of the patients. Samples of sputum that had been spontaneously expectorated in the morning were homogenized by incubation at 37°C for 15 minutes with an equal volume of 0.1 percent dithiothreitol (Sputolysin, Calbiochem). Serial dilutions of homogenized sputum in phosphate-buffered saline were placed on blood, chocolate, and MacConkey agar plates. Bacterial identification was performed with the use of standard techniques. If Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae was present, up to 10 individual colonies of each bacterial species were isolated and saved as frozen stocks at –70°C.
Sputum isolates were classified as potential pathogens or as normal flora. Potential pathogens were H. influenzae, M. catarrhalis, S. pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and other gram-negative rods.18,19 Other bacterial species were classified as normal flora.
Molecular Typing
Isolates of H. influenzae were typed by polyacrylamide-gel electrophoresis of cell lysates, as previously described.20 This method is based largely on the mobility of major outer-membrane proteins that vary among strains.21 Because of the occurrence of multiple strains in a single sputum sample, every available isolate (a total of 2159 isolates from 375 sputum samples) of H. influenzae were typed. To determine whether more than one strain was present in a sputum sample, 10 isolates from 25 sputum samples with M. catarrhalis and the same number with S. pneumoniae were individually typed. A single strain was present in every instance. Therefore, single isolates of M. catarrhalis, S. pneumoniae, and P. aeruginosa strains were subsequently typed by pulsed-field gel electrophoresis, as previously described.22-25 A single isolate of P. aeruginosa had been saved from each sputum sample as indicated by the study protocol, and additional isolates were therefore not available for typing.
Each strain was categorized as old or new on the basis of molecular typing. A new strain was one that had not been isolated from sputum samples obtained previously from an individual patient. An old strain was one that had been isolated from sputum obtained from a previous visit. In six instances, a strain isolated at the time of an exacerbation had been identified as a new strain at a visit less than four weeks earlier, when the patient had had stable disease. These strains were classified as new strains for the exacerbation-related visit.
Statistical Analysis
The unit of analysis was the clinic visit. The relative risk of an exacerbation when a pathogen or a new strain was present was calculated with the use of generalized estimating equations to take into account the patients' repeated visits (S Plus 6.0, Insightful).26 An unstructured correlation matrix was used. The absence of an exacerbation, a pathogen, or a new strain was coded as 0, and the presence as 1. The coefficient of the relation between the risk of an exacerbation due to a pathogen or a new strain was the log of the relative risk when a quasilikelihood approach was used with a logarithmic-link function.27 An alternative approach is to estimate the odds ratio with the use of conditional logistic regression. With this alternative approach, the results were similar (not shown) and did not affect our overall conclusions.
To determine the effect of the influenza season, the months of December, January, February, and March were designated as the influenza season and coded as 1, and the other months were coded as 0. The coding for influenza season was added to the pathogen or new strain as another predictor variable for the risk of an exacerbation, together with a term for the interaction between the two predictor variables.
Results
Characteristics of the Patients and the Visits
The majority of the patients were elderly men with moderate-to-severe chronic obstructive pulmonary disease (Table 1Table 1
Base-Line Characteristics of 81 Patients with Chronic Obstructive Pulmonary Disease.). At all but one visit, the assessment of the patient was completed. The characteristics of these 1975 completed visits are shown in Table 2Table 2
Characteristics of 1975 Completed Clinic Visits.. Sputum was not available at a total of 148 clinic visits (11 visits during exacerbations and 137 at the time of stable disease). Absence of sputum was significantly less frequent during exacerbations than during stable disease (2.9 percent vs. 8.6 percent, P<0.001).For 26 exacerbations, the patient had received at least one dose of an antibiotic within 48 hours before the clinic visit. Pathogens were isolated in sputum samples obtained at 8 (30.8 percent) of these 26 visits, as compared with 134 (39.8 percent) of 337 visits during exacerbations for which there had been no antibiotic treatment within the previous 48 hours, but the effect of antibiotic use on the rate of isolation of pathogens was not statistically significant (P=0.43). Visits during exacerbations preceded by antibiotic treatment were therefore included in the data analysis. The influenza season did not significantly affect the incidence of exacerbations, the rate of isolation of pathogens, or the rate of isolation of new strains.
Excluding the 1 incomplete visit and the 148 visits at which sputum samples were not obtained, 1827 visits were analyzed for the association between bacterial isolation and exacerbation. Pathogenic bacteria were isolated from sputum samples obtained at 601 of the 1827 visits (32.9 percent). Isolation of a bacterial pathogen was associated with a significant increase in the incidence of exacerbations. An exacerbation was present in 142 of the 601 visits at which pathogens were isolated from sputum (23.6 percent), as compared with 221 of 1226 visits at which no pathogens were isolated from sputum (18.0 percent; P<0.001); the relative risk of an exacerbation for patients with pathogens was 1.44 (95 percent confidence interval, 1.24 to 1.68) (Table 3Table 3
Relative Risk of an Exacerbation According to Whether a Bacterial Pathogen Was Isolated.). An analysis of individual bacterial species showed a significant increase in the frequency of exacerbations with isolation of M. catarrhalis and S. pneumoniae. Isolation of H. influenzae, P. aeruginosa, and gram-negative bacilli was not associated with an increased frequency of exacerbations. Isolation of S. aureus was associated with a decreased frequency of exacerbation (P=0.007; relative risk, 0.15; 95 percent confidence interval, 0.04 to 0.60); however, this finding requires confirmation with a larger number of isolates.Acute Exacerbations and Acquisition of New Strains
Two examples of molecular typing and time lines are shown in Figure 1Figure 1
Time Lines and Molecular Typing for Two Patients.. Data were analyzed to test the hypothesis that acquisition of a new bacterial strain was associated with an exacerbation. The 148 visits at which sputum was not available were excluded because of the absence of bacteriologic data. The 80 initial clinic visits at which sputum was obtained were excluded because of our inability to determine whether the strain isolated from sputum was new or old. In addition, visits associated with an ongoing exacerbation that had been present at the time of the previous visit (a total of 39 visits) were excluded. S. aureus and gram-negative bacilli other than P. aeruginosa were not subjected to molecular typing because of the small number of strains available. Therefore, the 47 visits at which these species were the only pathogens isolated were excluded. For six visits during stable disease, acquisition of a new strain was followed by an exacerbation within four weeks with the same strain of bacteria isolated from sputum; these six visits were also excluded from the analysis. Therefore, a total of 1353 visits during stable disease and 302 visits during exacerbations were included in the analysis of the relation between strain acquisition and exacerbation.Isolation of a new strain of a pathogen was associated with a significant increase in the frequency of exacerbation. Eighty-nine of 270 visits at which new strains were isolated (33.0 percent) were associated with exacerbations, as compared with 213 of 1385 visits at which no new strains were isolated (15.4 percent; P<0.001; relative risk, 2.15; 95 percent confidence interval, 1.83 to 2.53) (Table 4Table 4
Relative Risk of an Exacerbation According to Whether a New Strain of Bacterial Pathogen Was Isolated.). The relative risk of an exacerbation in association with the isolation of a new strain of H. influenzae was 1.69 (95 percent confidence interval, 1.37 to 2.09; P<0.001). This finding contrasts with the absence of an association between the isolation of H. influenzae and an exacerbation (Table 3), demonstrating the importance of strain analysis. The relative risk of an exacerbation in association with the isolation of a new strain was 2.96 for M. catarrhalis (95 percent confidence interval, 2.39 to 3.67; P<0.001) and 1.77 for S. pneumoniae (95 percent confidence interval, 1.14 to 2.75; P=0.01). For these two pathogens, strain analysis magnified the association shown by analysis of the rate of isolation and the occurrence of an exacerbation (Table 3). Isolation of new strains of P. aeruginosa was not associated with exacerbations (relative risk, 0.61; 95 percent confidence interval, 0.21 to 1.82; P=0.38).Discussion
We used molecular typing of bacteria in a prospective study to test the hypothesis that the acquisition of new strains of bacterial pathogens is associated with exacerbations of chronic obstructive pulmonary disease. Such an association was demonstrated for H. influenzae, M. catarrhalis, and S. pneumoniae — the three major pathogens implicated in acute exacerbations of chronic obstructive pulmonary disease. The findings for S. pneumoniae need to be confirmed with a larger number of isolates. With P. aeruginosa, no association was observed; however, the number of isolates was small.
An association between the acquisition of a new strain and an exacerbation of disease does not prove causation. However, this finding contributes to the growing body of evidence that bacteria cause a substantial proportion of exacerbations. This body of evidence includes data obtained during exacerbations that show an association between increased airway inflammation in sputum and the isolation of bacterial pathogens,28,29 the development of a strain-specific immune response to the infecting bacterial strains,14 and the isolation of bacteria in substantial numbers from specimens obtained from the distal airways by bronchoscopy.18,30
Our observations suggest a mechanism that explains recurrent bacterial exacerbations of chronic obstructive pulmonary disease. We speculate that a strain-specific protective immune response develops after an exacerbation, leaving the patient susceptible to infection by other strains of the same bacterial species.8,14,31 Acquisition of a strain to which the patient is susceptible leads to an exacerbation.15
The limitations of our study include a reliance on analysis of sputum samples, which have low sensitivity and specificity. In a large prospective study, however, the use of more invasive methods for repeated sampling of lower-airway secretions is impractical. The frequency of isolation of S. pneumoniae was relatively low in this study. However, several other investigators have reported a low rate of isolation of this pathogen in association with acute exacerbations, particularly in patients with moderate-to-severe chronic obstructive pulmonary disease, which the majority of our patients had.32-34
Some of our patients had new bacterial strains in the absence of an exacerbation. One possible explanation is that these strains were less virulent than the strains associated with exacerbations and therefore induced a less intense host inflammatory response that did not cause symptoms. Indeed, strains of H. influenzae vary in their ability to induce inflammatory responses in tissue culture.35 Another possible explanation is that these new strains did cause symptoms, but they were not severe enough to prompt the patient to seek medical help. Seemungal et al. studied daily symptoms and peak expiratory flows in patients with chronic obstructive pulmonary disease and found that as many as half the exacerbations were not reported by the patients.2
Some exacerbations occur in the absence of bacteria in sputum. In addition, in our study, the strain isolated was a preexisting strain in approximately a quarter of the visits during exacerbations when bacterial pathogens were present in sputum. There are several possible mechanisms for these exacerbations. Respiratory-virus infection is present in a third of exacerbations.31 There is serologic evidence of infection with Mycoplasma pneumoniae or Chlamydia pneumoniae in 5 to 10 percent of exacerbations.31 Our study design was limited by the fact that we did not identify infections with viruses and atypical bacteria. Another possible mechanism for exacerbations caused by preexisting strains is a modification of the antigenic structure that allows the strain to evade the host immune response and multiply in the airways, causing increased inflammation and therefore symptoms.36 Such a modification, which occurs with H. influenzae in animal models and in patients with chronic obstructive pulmonary disease, requires further investigation.36
In summary, the isolation of new strains of H. influenzae, M. catarrhalis, and S. pneumoniae in patients with chronic obstructive pulmonary disease was associated with acute exacerbations. This finding provides evidence that many acute exacerbations of chronic obstructive pulmonary disease are due to bacterial infection.
Supported by a Merit Review grant from the Department of Veterans Affairs.
We are indebted to Aimee Brauer, Aubrey Walters, Catherine Wrona, Celina Braciak, Norine Kuhn, Karen Muscarella, Sheru Kansal, Erin Murphy, Erin MacNamara, Carla Kinyon, and Sateesh Veeramachaneni for their assistance with laboratory studies; to Adeline Thurston for secretarial support; and to Joseph Mylotte, M.D., for helpful comments.
Source Information
From the Divisions of Pulmonary and Critical Care Medicine (S.S., B.J.B.G.) and Infectious Diseases (T.F.M.), Department of Medicine, the Department of Microbiology (T.F.M.), and the Departments of Physiology and Biophysics and Social and Preventive Medicine (B.J.B.G.), State University of New York; and the Veterans Affairs Western New York Healthcare System (S.S., N.E., B.J.B.G., T.F.M.) — both in Buffalo, N.Y.
Address reprint requests to Dr. Sethi at the Veterans Affairs Western New York Healthcare System (151), 3495 Bailey Ave., Buffalo, NY 14215, or at ssethi@buffalo.edu.
- References
References
1
Burrows B ,Earle RH . Course and prognosis of chronic obstructive lung disease: a prospective study of 200 patients. N Engl J Med 1969;280:397-404
Full Text | Web of Science | Medline2
Seemungal TAR ,Donaldson GC ,Bhowmik A ,Jeffries DJ ,Wedzicha JA . Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1608-1613
Web of Science | Medline3
Connors AF Jr ,Dawson NV ,Thomas C , et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. Am J Respir Crit Care Med 1996;154:959-967[Erratum, Am J Respir Crit Care Med 1997;155:386.]
Web of Science | Medline4
Seneff MG ,Wagner DP ,Wagner RP ,Zimmerman JE ,Knaus WA . Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA 1995;274:1852-1857
CrossRef | Web of Science | Medline5
Smith CB ,Golden C ,Klauber MR ,Kanner R ,Renzetti A . Interactions between viruses and bacteria in patients with chronic bronchitis. J Infect Dis 1976;143:552-561
CrossRef6
Gump DW ,Phillips CA ,Forsyth BR ,McIntosh K ,Lamborn KR ,Stouch WH . Role of infection in chronic bronchitis. Am Rev Respir Dis 1976;113:465-474
Web of Science | Medline7
Tager I ,Speizer FE . Role of infection in chronic bronchitis. N Engl J Med 1975;292:563-571
Full Text | Web of Science | Medline8
Murphy TF ,Sethi S . Bacterial infection in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992;146:1067-1083
Web of Science | Medline9
Hirschmann JV . Do bacteria cause exacerbations of COPD? Chest 2000;118:193-203
CrossRef | Web of Science | Medline10
Murphy TF ,Sethi S ,Niederman MS . The role of bacteria in exacerbations of COPD: a constructive view. Chest 2000;118:204-209
CrossRef | Web of Science | Medline11
McHardy VU ,Inglis JM ,Calder MA , et al. A study of infective and other factors in exacerbations of chronic bronchitis. Br J Dis Chest 1980;74:228-238
CrossRef | Medline12
Fagon J-Y ,Chastre J . Severe exacerbations of COPD patients: the role of pulmonary infections. Semin Respir Infect 1996;11:109-118
Medline13
Maslow JN ,Mulligan ME ,Arbeit RD . Molecular epidemiology: application of contemporary techniques to the typing of microorganisms. Clin Infect Dis 1993;17:153-164
CrossRef | Web of Science | Medline14
Yi K ,Sethi S ,Murphy TF . Human immune response to nontypeable Haemophilus influenzae in chronic bronchitis. J Infect Dis 1997;176:1247-1252
CrossRef | Web of Science | Medline15
Faden H ,Bernstein J ,Brodsky L , et al. Otitis media in children. I. The systemic immune response to nontypeable Hemophilus influenzae. J Infect Dis 1989;160:999-1004
CrossRef | Web of Science | Medline16
Chapman AJ Jr ,Musher DM ,Jonsson S ,Clarridge JE ,Wallace RJ Jr . Development of a bactericidal antibody during Branhamella catarrhalis infection. J Infect Dis 1985;151:878-882
CrossRef | Web of Science | Medline17
American Thoracic Society
Web of Science | Medline18
Monso E ,Ruiz J ,Rosell A , et al. Bacterial infection in chronic obstructive pulmonary disease: a study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med 1995;152:1316-1320
Web of Science | Medline19
Soler N ,Ewig S ,Torres A ,Filella X ,Gonzalez J ,Zaubet A . Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease. Eur Respir J 1999;14:1015-1022
CrossRef | Web of Science | Medline20
Murphy TF ,Sethi S ,Klingman KL ,Brueggemann AB ,Doern GV . Simultaneous respiratory tract colonization by multiple strains of nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease: implications for antibiotic therapy. J Infect Dis 1999;180:404-409
CrossRef | Web of Science | Medline21
Murphy TF ,Dudas KC ,Mylotte J ,Apicella MA . A subtyping system for nontypable Haemophilus influenzae based on outer-membrane proteins. J Infect Dis 1983;147:838-846
CrossRef | Web of Science | Medline22
Klingman KL ,Pye A ,Murphy TF ,Hill SL . Dynamics of respiratory tract colonization by Branhamella catarrhalis in bronchiectasis. Am J Respir Crit Care Med 1995;152:1072-1078
Web of Science | Medline23
Lefevre JC ,Faucon G ,Sicard AM ,Gasc AM . DNA fingerprinting of Streptococcus pneumoniae strains by pulsed-field gel electrophoresis. J Clin Microbiol 1993;31:2724-2728
Web of Science | Medline24
Grothues D ,Koopmann U ,von der Hardt H ,Tummler B . Genome fingerprinting of Pseudomonas aeruginosa indicates colonization of cystic fibrosis siblings with closely related strains. J Clin Microbiol 1988;26:1973-1977
Web of Science | Medline25
Speijer H ,Savelkoul PHM ,Bonten MJ ,Stobberingh EE ,Tjhie JHT . Application of different genotyping methods for Pseudomonas aeruginosa in a setting of endemicity in an intensive care unit. J Clin Microbiol 1999;37:3654-3661
Web of Science | Medline26
Zeger SL ,Liang KY . Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986;42:121-130
CrossRef | Web of Science | Medline27
Wacholder S . Binomial regression in GLIM: estimating risk ratios and risk differences. Am J Epidemiol 1986;123:174-184
Web of Science | Medline28
Sethi S ,Muscarella K ,Evans N ,Klingman KL ,Grant BJB ,Murphy TF . Airway inflammation and etiology of acute exacerbations of chronic bronchitis. Chest 2000;118:1557-1565
CrossRef | Web of Science | Medline29
Hill AT ,Campbell EJ ,Bayley DL ,Hill SL ,Stockley RA . Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with α1-antitrypsin deficiency (PiZ). Am J Respir Crit Care Med 1999;160:1968-1975
Web of Science | Medline30
Fagon J-Y ,Chastre J ,Trouillet J-L , et al. Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis: use of the protected specimen brush technique in 54 mechanically ventilated patients. Am Rev Respir Dis 1990;142:1004-1008
Web of Science | Medline31
Sethi S . Infectious etiology of acute exacerbations of chronic bronchitis. Chest 2000;117:Suppl 2:380S-385S
CrossRef | Web of Science | Medline32
Obaji A ,Sethi S . Acute exacerbations of chronic bronchitis: what role for the new fluoroquinolones? Drugs Aging 2001;18:1-11
CrossRef | Web of Science | Medline33
Eller J ,Ede A ,Schaberg T ,Niederman MS ,Mauch H ,Lode H . Infective exacerbations of chronic bronchitis: relation between bacteriologic etiology and lung function. Chest 1998;113:1542-1548
CrossRef | Web of Science | Medline34
Miravitlles M ,Espinosa C ,Fernandez-Laso E ,Martos JA ,Maldonado JA ,Gallego M . Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 1999;116:40-46
CrossRef | Web of Science | Medline35
Bresser P ,van Alphen L ,Habets FJM , et al. Persisting Haemophilus influenzae strains induce lower levels of interleukin-6 and interleukin-8 in H292 lung epithelial cells than nonpersisting strains. Eur Respir J 1997;10:2319-2326
CrossRef | Web of Science | Medline36
Duim B ,van Alphen L ,Eijk PP ,Jansen HM ,Dankert J . Antigenic drift of non-encapsulated Haemophilus influenzae major outer membrane protein P2 in patients with chronic bronchitis is caused by point mutations. Mol Microbiol 1994;11:1181-1189
CrossRef | Web of Science | Medline
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Citing Articles
1
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CrossRef2
Yvonne J Huang, Susan V Lynch. (2011) The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications. Expert Review of Respiratory Medicine 5:6, 809-821
CrossRef3
Angela M. Abbatecola, Alessia Fumagalli, Daniela Bonardi, Enrico E. Guffanti. (2011) Practical management problems of chronic obstructive pulmonary disease in the elderly. Current Opinion in Pulmonary Medicine 17, S49-S54
CrossRef4
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CrossRef5
P. Zarogoulidis, N. Papanas, I. Kioumis, E. Chatzaki, E. Maltezos, K. Zarogoulidis. (2011) Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases. European Journal of Clinical Pharmacology
CrossRef6
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CrossRef7
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CrossRef8
M. Woodhead, F. Blasi, S. Ewig, J. Garau, G. Huchon, M. Ieven, A. Ortqvist, T. Schaberg, A. Torres, G. van der Heijden, R. Read, T. J. M. Verheij, . (2011) Guidelines for the management of adult lower respiratory tract infections - Summary. Clinical Microbiology and Infection 17, 1-24
CrossRef9
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CrossRef10
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CrossRef13
D.I. Krimmer, B.G.G. Oliver. (2011) What can in vitro models of COPD tell us?. Pulmonary Pharmacology & Therapeutics 24:5, 471-477
CrossRef14
M.E. García Leoni, B. Macías Bou, L. Martín González, E. Martínez Larrull. (2011) Infecciones respiratorias. Medicine - Programa de Formación Médica Continuada Acreditado 10:88, 5947-5954
CrossRef15
Klaus F Rabe, Jadwiga A Wedzicha. (2011) Controversies in treatment of chronic obstructive pulmonary disease. The Lancet 378:9795, 1038-1047
CrossRef16
Guy G Brusselle, Guy F Joos, Ken R Bracke. (2011) New insights into the immunology of chronic obstructive pulmonary disease. The Lancet 378:9795, 1015-1026
CrossRef17
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CrossRef18
Marc Miravitlles. (2011) Cough and sputum production as risk factors for poor outcomes in patients with COPD. Respiratory Medicine 105:8, 1118-1128
CrossRef19
TETYANA ZAKHARKINA, A.-REMBERT KOCZULLA, OLGA MARDANOVA, AKIRA HATTESOHL, ROBERT BALS. (2011) Detection of microorganisms in exhaled breath condensate during acute exacerbations of COPD. Respirology 16:6, 932-938
CrossRef20
Sofya Tokman, Philipp Schuetz, Stephen Bent. (2011) Procalcitonin-guided antibiotic therapy for chronic obstructive pulmonary disease exacerbations. Expert Review of Anti-infective Therapy 9:6, 727-735
CrossRef21
Rodrigo Cavallazzi, Sonal Singh. (2011) Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease: How Significant is the Risk of Pneumonia and Should It Impact Use of Inhaled Corticosteroids?. Current Infectious Disease Reports 13:3, 296-301
CrossRef22
S. Sethi. (2011) Molecular Diagnosis of Respiratory Tract Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Clinical Infectious Diseases 52:Supplement 4, S290-S295
CrossRef23
C. J. Harvey, R. K. Thimmulappa, S. Sethi, X. Kong, L. Yarmus, R. H. Brown, D. Feller-Kopman, R. Wise, S. Biswal. (2011) Targeting Nrf2 Signaling Improves Bacterial Clearance by Alveolar Macrophages in Patients with COPD and in a Mouse Model. Science Translational Medicine 3:78, 78ra32-78ra32
CrossRef24
DAVID S. HUI, MARGARET IP, THOMAS LING, SHAN-CHWEN CHANG, CHUN-HSING LIAO, CHUL-GYU YOO, DEOG-KYEOM KIM, HO-IL YOON, VISIT UDOMPANICH, SOMKID MOGMEUD, RAZAK MUTTALIF, AZMI M. SALLEH, CAMILO ROA, MYRNA MENDOZA, CONCEPCION FAJARDO-ANG, PRIYANTI SOEPANDI, FATHIYAH ISBANIAH, ERLINA BURHAN, PRATIWI SUDARMONO, HADIARTO MANGUNNEGORO, HANS H. LIU. (2011) A multicentre surveillance study on the characteristics, bacterial aetiologies and in vitro antibiotic susceptibilities in patients with acute exacerbations of chronic bronchitis. Respirology 16:3, 532-539
CrossRef25
Lorenzo Corbetta, Fabrizio Luppi, Raffaele A. Incalzi. (2011) Linee guida sulla BPCO non associata a comorbilità croniche. Italian Journal of Medicine 5:1, 14-21
CrossRef26
Fabrizio Luppi, Bianca Beghè, Pietro Roversi. (2011) Le infezioni come comorbilità della BPCO. Italian Journal of Medicine 5:1, 135-141
CrossRef27
Thomas E. Sussan, Shyam Biswal. 2011. Smoking and COPD and Other Respiratory Diseases. , 167-190.
CrossRef28
R. Pesek, R. Lockey. (2011) Vaccination of adults with asthma and COPD. Allergy 66:1, 25-31
CrossRef29
Catherina L. CHANG, Glenda D. SULLIVAN, Noel C. KARALUS, Graham D. MILLS, John D. MCLACHLAN, Robert J. HANCOX. (2011) Predicting early mortality in acute exacerbation of chronic obstructive pulmonary disease using the CURB65 score. Respirology 16:1, 146-151
CrossRef30
Rafael Cantón, Ana Fernández Olmos, Elia Gómez G. de la Pedrosa, Rosa Del Campo, María Antonia Meseguer. (2011) Infección bronquial crónica: el problema de Pseudomonas aeruginosa. Archivos de Bronconeumología 47, 8-13
CrossRef31
Timothy F Murphy, Aimee L Brauer. (2011) Expression of urease by Haemophilus influenzae during human respiratory tract infection and role in survival in an acid environment. BMC Microbiology 11:1, 183
CrossRef32
P. Morey, V. Cano, P. Marti-Lliteras, A. Lopez-Gomez, V. Regueiro, C. Saus, J. A. Bengoechea, J. Garmendia. (2011) Evidence for a non-replicative intracellular stage of nontypable Haemophilus influenzae in epithelial cells. Microbiology 157:1, 234-250
CrossRef33
Gerd Döring, Iyer G. Parameswaran, Timothy F. Murphy. (2011) Differential adaptation of microbial pathogens to airways of patients with cystic fibrosis and chronic obstructive pulmonary disease. FEMS Microbiology Reviews 35:1, 124-146
CrossRef34
Bryan Corrin, Andrew G. Nicholson. 2011. Diseases of the conductive airways. , 91-134.
CrossRef35
Julia AE Walters, Sabin Smith, Phillippa Poole, Robert H Granger, Richard Wood-Baker, Julia AE Walters. 2010. Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease. .
CrossRef36
A Ruth Foxwell, Allan W Cripps, Keith BG Dear, A Ruth Foxwell. 2010. Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis. .
CrossRef37
Himanshu Desai, Sandra Richter, Gary Doern, Kris Heilmann, Cassie Dohrn, Antoinette Johnson, Aimee Brauer, Timothy Murphy, Sanjay Sethi. (2010) Antibiotic Resistance in Sputum Isolates of Streptococcus pneumoniae in Chronic Obstructive Pulmonary Disease is Related to Antibiotic Exposure. COPD: Journal of Chronic Obstructive Pulmonary Disease 7:5, 337-344
CrossRef38
Andrea D. Valderrey, María José Pozuelo, Pedro A. Jiménez, María D. Maciá, Antonio Oliver, Rafael Rotger. (2010) Chronic colonization by Pseudomonas aeruginosa of patients with obstructive lung diseases: cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. Diagnostic Microbiology and Infectious Disease 68:1, 20-27
CrossRef39
Dong Wang, Ying Wang, You-ning Liu. (2010) Experimental pulmonary infection and colonization of Haemophilus influenzae in emphysematous hamsters. Pulmonary Pharmacology & Therapeutics 23:4, 292-299
CrossRef40
C M Lloyd, J R Murdoch. (2010) Tolerizing allergic responses in the lung. Mucosal Immunology 3:4, 334-344
CrossRef41
J. M. A. Daniels, C. S. De Graaff, F. Vlaspolder, D. Snijders, H. M. Jansen, W. G. Boersma. (2010) Sputum colour reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of chronic obstructive pulmonary disease. Clinical Microbiology and Infection 16:6, 583-588
CrossRef42
Sanjay Sethi. (2010) Antibiotics in acute exacerbations of chronic bronchitis. Expert Review of Anti-infective Therapy 8:4, 405-417
CrossRef43
Robert C. Read. 2010. Bacterial Infections of the Lower Respiratory Tract. .
CrossRef44
Sidney S. Braman, Muhanned Abu-Hijleh. (2010) The Spectrum of Nonasthmatic Inflammatory Airway Diseases in Adults. Otolaryngologic Clinics of North America 43:1, 131-146
CrossRef45
Tadashi Okabe, Yoshitaka Yamazaki, Miho Shiotani, Takefumi Suzuki, Mayumi Shiohara, Eriko Kasuga, Shigeyuki Notake, Hideji Yanagisawa. (2010) An amino acid substitution in PBP-3 in Haemophilus influenzae associate with the invasion to bronchial epithelial cells. Microbiological Research 165:1, 11-20
CrossRef46
Seung Wook Jeong, Jae Hee Lee, Keum Ju Choi, Yup Hwangbo, Yi Young Kim, Yun Ji Lee, Won Kyung Yoon, Min Kim, Sung Ick Cha, Jae Yong Park, Tae Hoon Jung, Chang Ho Kim. (2010) Comparisons of Clinical Characteristics and Outcomes in COPD Patients Hospitalized with Community-acquired Pneumonia and Acute Exacerbation. Tuberculosis and Respiratory Diseases 69:1, 31
CrossRef47
Miguel Ángel Martínez García, Juan José Soler Cataluña. (2010) EPOC y bronquiectasias. Archivos de Bronconeumología 46, 11-17
CrossRef48
Laura A. Novotny, Leanne D. Adams, D. Richard Kang, Gregory J. Wiet, Xueya Cai, Sanjay Sethi, Timothy F. Murphy, Lauren O. Bakaletz. (2009) Epitope mapping immunodominant regions of the PilA protein of nontypeable Haemophilus influenzae (NTHI) to facilitate the design of two novel chimeric vaccine candidates. Vaccine 28:1, 279-289
CrossRef49
G. Iyer Parameswaran, Timothy F. Murphy. (2009) Chronic Obstructive Pulmonary Disease. Drugs & Aging 26:12, 985-995
CrossRef50
Elizabeth A. Ruckdeschel, Aimee L. Brauer, Antoinette Johnson, Timothy F. Murphy. (2009) Characterization of proteins Msp22 and Msp75 as vaccine antigens of Moraxella catarrhalis. Vaccine 27:50, 7065-7072
CrossRef51
Jodie L. Simpson, Simon Phipps, Peter G. Gibson. (2009) Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis. Pharmacology & Therapeutics 124:1, 86-95
CrossRef52
Shoab A. Nazir, Marcia L. Erbland. (2009) Chronic Obstructive Pulmonary Disease. Drugs & Aging 26:10, 813-831
CrossRef53
Chu-Lin Tsai, Carlos A. Camargo. (2009) Methodological considerations, such as directed acyclic graphs, for studying “acute on chronic” disease epidemiology: Chronic obstructive pulmonary disease example. Journal of Clinical Epidemiology 62:9, 982-990
CrossRef54
M Laura Perez Vidakovics, Kristian Riesbeck. (2009) Virulence mechanisms of Moraxella in the pathogenesis of infection. Current Opinion in Infectious Diseases 22:3, 279-285
CrossRef55
Jordan Minov, Jovanka Karadzinska-Bislimovska, Tatjana Petrova, Kristin Vasilevska, Snezana Risteska-Kuc, Saso Stoleski, Dragan Mijakoski. (2009) Efficacy and Tolerability of Various Antimicrobial Regimens in the Treatment of Exacerbations of Chronic Bronchitis and Chronic Obstructive Pulmonary Disease in Outpatients. Macedonian Journal of Medical Sciences 2:2, 115-120
CrossRef56
Timothy F Murphy. (2009) Vaccine development for Moraxella catarrhalis : rationale, approaches and challenges. Expert Review of Vaccines 8:6, 655-658
CrossRef57
Timothy F Murphy. (2009) Pseudomonas aeruginosa in adults with chronic obstructive pulmonary disease. Current Opinion in Pulmonary Medicine 15:2, 138-142
CrossRef58
Daiana Stolz, Michael Tamm. (2009) Discriminate use of antibiotics for exacerbation of COPD. Current Opinion in Pulmonary Medicine 15:2, 126-132
CrossRef59
Judith Garcia-Aymerich, Àlvar Agustí, Joan A. Barberà, José Belda, Eva Farrero, Antoni Ferrer, Jaume Ferrer, Juan B. Gáldiz, Joaquim Gea, Federico P. Gómez, Eduard Monsó, Josep Morera, Josep Roca, Jaume Sauleda, Josep M. Antó. (2009) La heterogeneidad fenotípica de la EPOC. Archivos de Bronconeumología 45:3, 129-138
CrossRef60
Lakshmi Durairaj, Zeinab Mohamad, Janice L. Launspach, Alix Ashare, James Y. Choi, Srinivasan Rajagopal, Gary V. Doern, Joseph Zabner. (2009) Patterns and density of early tracheal colonization in intensive care unit patients. Journal of Critical Care 24:1, 114-121
CrossRef61
K L Ostberg, M W Russell, T F Murphy. (2009) Mucosal immunization of mice with recombinant OMP P2 induces antibodies that bind to surface epitopes of multiple strains of nontypeable Haemophilus influenzae. Mucosal Immunology 2:1, 63-73
CrossRef62
Jadwiga A. Wedzicha. 2009. Acute Exacerbations of COPD. , 837-845.
CrossRef63
Simon D. Message, Sebastian L. Johnston. 2009. Infections. , 471-493.
CrossRef64
Sanjay Sethi. 2009. Antibiotics. , 663-676.
CrossRef65
Seok‐Mo Heo, Elaine M. Haase, Alan J. Lesse, Steven R. Gill, Frank A. Scannapieco. (2008) Genetic Relationships between Respiratory Pathogens Isolated from Dental Plaque and Bronchoalveolar Lavage Fluid from Patients in the Intensive Care Unit Undergoing Mechanical Ventilation. Clinical Infectious Diseases 47:12, 1562-1570
CrossRef66
Laura Martínez‐Solano, María D. Macia, Alicia Fajardo, Antonio Oliver, Jose L. Martinez. (2008) Chronic Pseudomonas aeruginosa Infection in Chronic Obstructive Pulmonary Disease. Clinical Infectious Diseases 47:12, 1526-1533
CrossRef67
Sethi, Sanjay, Murphy, Timothy F., . (2008) Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease. New England Journal of Medicine 359:22, 2355-2365
Full Text68
Rachel Balder, Eric R. Lafontaine. 2008. Laboratory Maintenance of Moraxella catarrhalis. .
CrossRef69
Markus B. Sikkel, Jennifer K. Quint, Patrick Mallia, Jadwiga A. Wedzicha, Sebastian L. Johnston. (2008) Respiratory Syncytial Virus Persistence in Chronic Obstructive Pulmonary Disease. The Pediatric Infectious Disease Journal 27:Supplement, S63-S70
CrossRef70
P. T. King, J. Ngui, D. Gunawardena, P. W. Holmes, M. W. Farmer, S. R. Holdsworth. (2008) Systemic humoral immunity to non-typeable Haemophilus influenzae. Clinical & Experimental Immunology 153:3, 376-384
CrossRef71
Akitsugu Furumoto, Yasushi Ohkusa, Meng Chen, Kenji Kawakami, Hironori Masaki, Yoshiko Sueyasu, Tomoaki Iwanaga, Hisamichi Aizawa, Tsuyoshi Nagatake, Kazunori Oishi. (2008) Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease. Vaccine 26:33, 4284-4289
CrossRef72
Fulvio Braido, Michele Bellotti, Andrea De Maria, Mario Cazzola, Giorgio Walter Canonica. (2008) The role of Pneumococcal vaccine. Pulmonary Pharmacology & Therapeutics 21:4, 608-615
CrossRef73
Peter N Black. (2008) Role of antibiotics in the management of chronic obstructive pulmonary disease. Expert Review of Respiratory Medicine 2:2, 235-243
CrossRef74
Saad Nseir, Florence Ader. (2008) Prevalence and outcome of severe chronic obstructive pulmonary disease exacerbations caused by multidrug-resistant bacteria. Current Opinion in Pulmonary Medicine 14:2, 95-100
CrossRef75
Mario Cazzola, Paola Rogliani, Giacomo Curradi. (2008) Bacterial extracts for the prevention of acute exacerbations in chronic obstructive pulmonary disease: A point of view. Respiratory Medicine 102:3, 321-327
CrossRef76
Wei Yang Chou, Amir Soltani, Mei-Jo Sung, Julia AE Walters, Richard Wood-Baker, Wei Yang Chou. 2008. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. .
CrossRef77
John R. Hurst, Jadwiga A. Wedzicha. 2008. Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. , 517-521.
CrossRef78
Huahao Shen, Hiroki Yoshida, Fugui Yan, Wen Li, Feng Xu, Huaqiong Huang, Hirofumi Jono, Jian-Dong Li. (2008) Synergistic induction of MUC5AC mucin by nontypeable Haemophilus influenzae and Streptococcus pneumoniae. Biochemical and Biophysical Research Communications 365:4, 795-800
CrossRef79
C. L. Chang, R. J. Hancox. (2007) Reply. Internal Medicine Journal 37:12, 840-841
CrossRef80
Beat Müller, Philipp Schuetz, Andrej Trampuz. (2007) Circulating biomarkers as surrogates for bloodstream infections. International Journal of Antimicrobial Agents 30, 16-23
CrossRef81
Nicola A. Hanania, Amir Sharafkhaneh. (2007) Update on the Pharmacologic Therapy for Chronic Obstructive Pulmonary Disease. Clinics in Chest Medicine 28:3, 589-607
CrossRef82
John R. Hurst, Jadwiga A. Wedzicha. (2007) The Biology of a Chronic Obstructive Pulmonary Disease Exacerbation. Clinics in Chest Medicine 28:3, 525-536
CrossRef83
G. Iyer Parameswaran, Timothy F. Murphy. (2007) Infections in Chronic Lung Diseases. Infectious Disease Clinics of North America 21:3, 673-695
CrossRef84
Robert P. Baughman, Donna Winget, David P. Nicolau. (2007) Bronchoscopic Evaluation of Moxifloxacin Therapy in Acute Exacerbations of Chronic Bronchitis Previously Treated With Azithromycin. Journal of Bronchology 14:3, 144-148
CrossRef85
Patrick Petitpretz, Claudie Choné, François Trémolières. (2007) Levofloxacin 500mg once daily versus cefuroxime 250mg twice daily in patients with acute exacerbations of chronic obstructive bronchitis: clinical efficacy and exacerbation-free interval. International Journal of Antimicrobial Agents 30:1, 52-59
CrossRef86
P.-R. Burgel, N. Roche. (2007) La colonisation bactérienne est associée à une augmentation des marqueurs d’inflammation bronchique en période stable chez les patients atteints de BPCO et pourrait contribuer à la progression de la maladie. Revue des Maladies Respiratoires 24, 45-47
CrossRef87
Hortense Slevogt, Joachim Seybold, Krishna N. Tiwari, Andreas C. Hocke, Carola Jonatat, Solveig Dietel, Stefan Hippenstiel, Bernhard B. Singer, Sebastian Bachmann, Norbert Suttorp, Bastian Opitz. (2007) Moraxella catarrhalis is internalized in respiratory epithelial cells by a trigger-like mechanism and initiates a TLR2- and partly NOD1-dependent inflammatory immune response. Cellular Microbiology 9:3, 694-707
CrossRef88
Roger M. Echols, Glenn S. Tillotson, Thomas M. File. (2007) Antibiotic Development-D??j?? Vu. Infectious Diseases in Clinical Practice 15:2, 75-78
CrossRef89
Antonio Anzueto, William R. Bishai, Sudha Pottumarthy. (2007) Role of oral extended-spectrum cephems in the treatment of acute exacerbation of chronic bronchitis. Diagnostic Microbiology and Infectious Disease 57:3, S31-S38
CrossRef90
Raina T. Gergova, Ianko D. Iankov, Iana H. Haralambieva, Ivan G. Mitov. (2007) Bactericidal Monoclonal Antibody Against Moraxella catarrhalis Lipooligosaccharide Cross-Reacts with Haemophilus Spp.. Current Microbiology 54:2, 85-90
CrossRef91
Marc Miravitlles. (2007) Tratamiento farmacológico de las agudizaciones infecciosas de la EPOC. Archivos de Bronconeumología 43, 18-26
CrossRef92
James B. Kahn, Mohammed Khashab, Mary Ambruzs. (2007) Study entry microbiology in patients with acute bacterial exacerbation of chronic bronchitis in a clinical trial stratifying by disease severity*. Current Medical Research and Opinion 23:1, 1-7
CrossRef93
J. P. Hays, R. Gorkink, G. Simons, J. K. Peeters, K. Eadie, C. M. Verduin, H. Verbrugh, A. van Belkum. (2007) High-throughput amplification fragment length polymorphism (htAFLP) analysis identifies genetic lineage markers but not complement phenotype-specific markers in Moraxella catarrhalis. Clinical Microbiology and Infection 13:1, 55-62
CrossRef94
Marcus Zervos, Fernando J. Martinez, Guy W. Amsden, Constance D. Rothermel, Glenda Treadway. (2007) Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis. International Journal of Antimicrobial Agents 29:1, 56-61
CrossRef95
Ken M Kunisaki, Kathryn L Rice, Dennis E Niewoehner. (2007) Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in the Elderly. Drugs & Aging 24:4, 303-324
CrossRef96
Rodrigo Jiménez-García, Maria C. Ariñez-Fernandez, Valentín Hernández-Barrera, Marta M. Garcia-Carballo, Ángel Gil de Miguel, Pilar Carrasco-Garrido. (2007) Compliance with influenza and pneumococcal vaccination among patients with chronic obstructive pulmonary disease consulting their medical practitioners in Catalonia, Spain. Journal of Infection 54:1, 65-74
CrossRef97
Dang Duc Anh, Phan Le Thanh Huong, Kiwao Watanabe, Nguyen Thu Nguyet, Nguyen Thu Hien Anh, Ngo Thi Thi, Nguyen Tien Dung, Doan Mai Phuong, Susumu Tanimura, Yasushi Ohkusa, Tsuyoshi Nagatake, Hiroshi Watanabe, Kazunori Oishi. (2007) Increased Rates of Intense Nasopharyngeal Bacterial Colonization of Vietnamese Children with Radiological Pneumonia. The Tohoku Journal of Experimental Medicine 213:2, 167-172
CrossRef98
Jun Koyama, Kamruddin Ahmed, Jizi Zhao, Mariko Saito, Shozaburo Onizuka, Keita Oma, Kiwao Watanabe, Hiroshi Watanabe, Kazunori Oishi. (2007) Strain-Specific Pulmonary Defense Achieved after Repeated Airway Immunizations with Non-Typeable Haemophilus Influenzae in a Mouse Model. The Tohoku Journal of Experimental Medicine 211:1, 63-74
CrossRef99
Agustin RUIZ-GONZÁLEZ, Antonio GIMÉNEZ, Xavier GÓMEZ-ARBONÉS, Jorge SOLER-GONZÁLEZ, Virginia SÁNCHEZ, Miquel FALGUERA, Jose M. PORCEL. (2007) Open-label, randomized comparison trial of long-term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease. Respirology 12:1, 117-121
CrossRef100
2007. C. , 39-51.
CrossRef101
Dipak Chandy, Wilbert S. Aronow. (2006) Management of chronic obstructive pulmonary disease. Comprehensive Therapy 32:4, 230-235
CrossRef102
Soo-Mi Kweon, Beinan Wang, Davida Rixter, Jae Hyang Lim, Tomoaki Koga, Hajime Ishinaga, Lin-Feng Chen, Hirofumi Jono, Haidong Xu, Jian-Dong Li. (2006) Synergistic activation of NF-κB by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKKβ-IκBα, and p38 MAPK. Biochemical and Biophysical Research Communications 351:2, 368-375
CrossRef103
A Ruth Foxwell, Allan W Cripps, Keith BG Dear, A Ruth Foxwell. 2006. Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis. .
CrossRef104
M.S. Niederman, A. Anzueto, S. Sethi, S. Choudhri, A. Kureishi, D. Haverstock, R. Perroncel. (2006) Eradication of H. influenzae in AECB: A pooled analysis of moxifloxacin phase III trials compared with macrolide agents. Respiratory Medicine 100:10, 1781-1790
CrossRef105
Francesco Blasi, Santiago Ewig, Antoni Torres, Gerard Huchon. (2006) A review of guidelines for antibacterial use in acute exacerbations of chronic bronchitis. Pulmonary Pharmacology & Therapeutics 19:5, 361-369
CrossRef106
Christoph Wenisch. (2006) Akute Exazerbation bei COPD. Wiener klinische Wochenschrift Education 1:2, 85-91
CrossRef107
K. Dalhoff, H. Kothe. (2006) Antibiotikatherapie bei Exazerbation. Der Internist 47:9, 908-916
CrossRef108
Carles Llor, Josep Maria Cots, Amadeo Herreras. (2006) Bacterial Etiology of Chronic Bronchitis Exacerbations Treated by Primary Care Physicians. Archivos de Bronconeumología (English Edition) 42:8, 388-393
CrossRef109
Carles Llor, Josep Maria Cots, Amadeo Herreras. (2006) Etiología bacteriana de la agudización de la bronquitis crónica en atención primaria. Archivos de Bronconeumología 42:8, 388-393
CrossRef110
Amit Patel, Robert Wilson. (2006) Newer fluoroquinolones in the treatment of acute exacerbations of COPD. International Journal of COPD 1:3, 243-250
CrossRef111
Hortense Slevogt, Krishna N. Tiwari, Bernd Schmeck, Andreas Hocke, Bastian Opitz, Norbert Suttorp, Joachim Seybold. (2006) Adhesion of Moraxella catarrhalis to human bronchial epithelium characterized by a novel fluorescence-based assay. Medical Microbiology and Immunology 195:2, 73-83
CrossRef112
J. Mensa, A. Trilla. (2006) Should patients with acute exacerbation of chronic bronchitis be treated with antibiotics? Advantages of the use of fluoroquinolones. Clinical Microbiology and Infection 12:s3, 42-54
CrossRef113
Douglas W. Mapel, Judith S. Hurley, Douglas Roblin, Melissa Roberts, Kourtney J. Davis, Robert Schreiner, Floyd J. Frost. (2006) Survival of COPD patients using inhaled corticosteroids and long-acting beta agonists. Respiratory Medicine 100:4, 595-609
CrossRef114
Maria Szilasi, Tamás Dolinay, Zoltán Nemes, János Strausz. (2006) Pathology of chronic obstructive pulmonary disease. Pathology & Oncology Research 12:1, 52-60
CrossRef115
Nader Eldika, Sanjay Sethi. (2006) Role of nontypeable Haemophilus Influenzae in exacerbations and progression of chronic obstructive pulmonary disease. Current Opinion in Pulmonary Medicine 12:2, 118-124
CrossRef116
Richard Jacobs, Jeanine Wiener-Kronish. (2006) Endotracheal Tubes. Anesthesiology 104:2, 224-225
CrossRef117
Fernando J Martinez, MeiLan K Han, Kevin Flaherty, Jeffrey Curtis. (2006) Role of infection and antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease. Expert Review of Anti-infective Therapy 4:1, 101-124
CrossRef118
Mario Cazzola, Claudio Ferdinando Donner. (2006) The need for a new fluoroquinolone. Pulmonary Pharmacology & Therapeutics 19, 1-3
CrossRef119
M. Kolditz, G. Höffken. (2006) Akute Exazerbation der chronisch-obstruktiven Lungenerkrankung. Der Pneumologe 3:1, 28-36
CrossRef120
Francesco Blasi, Paolo Tarsia, Stefano Aliberti, PierAchille Santus, Luigi Allegra. (2006) Highlights on the appropriate use of fluoroquinolones in respiratory tract infections. Pulmonary Pharmacology & Therapeutics 19, 11-19
CrossRef121
W WANG, A ATTIA, L LIU, T ROSCHE, N WAGNER, E HANSEN. (2006) Development of a shuttle vector for Moraxella catarrhalis. Plasmid 55:1, 50-57
CrossRef122
Timothy F Murphy. (2005) Vaccine development for non-typeable Haemophilus influenzae and Moraxella catarrhalis : progress and challenges. Expert Review of Vaccines 4:6, 843-853
CrossRef123
Massoud Daheshia. (2005) Pathogenesis of chronic obstructive pulmonary disease (COPD). Clinical and Applied Immunology Reviews 5:5, 339-351
CrossRef124
Robert P. Rennie, Khalid H. Ibrahim. (2005) Antimicrobial Resistance in Haemophilus influenzae: How Can We Prevent the Inevitable? Commentary on Antimicrobial Resistance in H. influenzae Based on Data from the TARGETed Surveillance Program. Clinical Infectious Diseases 41:s4, S234-S238
CrossRef125
Sanjay Sethi, Douglas B. Schwartz. (2005) Impact of Acute Exacerbations on the Natural History of Chronic Obstructive Pulmonary Disease. Clinical Pulmonary Medicine 12:Supplement, S16-S18
CrossRef126
Mario Cazzola, Antonello Salzillo, Carlo De Giglio, Amedeo Piccolo, Clara Califano, Paolo Noschese. (2005) Treatment of acute exacerbation of severe-to-very severe COPD with azithromycin in patients vaccinated against Streptococcus pneumoniae. Respiratory Medicine 99:6, 663-669
CrossRef127
Sethi, Sanjay, Murphy, Timothy F., . (2005) RSV Infection — Not for Kids Only. New England Journal of Medicine 352:17, 1810-1812
Full Text128
Timothy F. Murphy, Charmaine Kirkham, Sanjay Sethi, Alan J. Lesse. (2005) Expression of a peroxiredoxinâglutaredoxin by Haemophilus influenzae in biofilms and during human respiratory tract infection. FEMS Immunology & Medical Microbiology 44:1, 81-89
CrossRef129
C. Lange. (2005) Bakteriell verursachte Exazerbation chronisch-obstruktiver Lungenerkrankungen (COPD). Der Pneumologe 2:2, 123-125
CrossRef130
Thomas M. File. (2005) Telithromycin new product overview. Journal of Allergy and Clinical Immunology 115:2, S361-S373
CrossRef131
Robert N Swanson, Alberto Lainez-Ventosilla, Maria C De Salvo, Michael W Dunne, Guy W Amsden. (2005) Once-Daily Azithromycin for 3 Days Compared with Clarithromycin for 10 Days for Acute Exacerbation of Chronic Bronchitis. Treatments in Respiratory Medicine 4:1, 31-39
CrossRef132
Sat Sharma, Nicholas Anthonisen. (2005) Role of Antimicrobial Agents in the Management??of Exacerbations of COPD. Treatments in Respiratory Medicine 4:3, 153-167
CrossRef133
Fernando J. Martinez. (2005) Acute exacerbation of chronic bronchitis: expanding short-course therapy. International Journal of Antimicrobial Agents 26, S156-S163
CrossRef134
Sanjay Sethi, Timothy F. Murphy. (2004) Acute exacerbations of chronic bronchitis: new developments concerning microbiology and pathophysiology—impact on approaches to risk stratification and therapy. Infectious Disease Clinics of North America 18:4, 861-882
CrossRef135
Michael S. Niederman. (2004) Editorial Commentary: Who Should Receive Antibiotics for Exacerbations of Chronic Bronchitis? A Plea for More Outcome‐Based Studies. Clinical Infectious Diseases 39:7, 987-989
CrossRef136
Gernot Rohde, Philippe Gevaert, Gabriele Holtappels, Irmgard Borg, Almut Wiethege, Umut Arinir, Gerhard Schultze-Werninghaus, Claus Bachert. (2004) Increased IgE-antibodies to Staphylococcus aureus enterotoxins in patients with COPD. Respiratory Medicine 98:9, 858-864
CrossRef137
EFM Wouters. (2004) Management of severe COPD. The Lancet 364:9437, 883-895
CrossRef138
Thomas J. Ferro. (2004) Antibiotic Use-Changing Paradigms. Infectious Diseases in Clinical Practice 12, S4-S7
CrossRef139
P.C Appelbaum, S.H Gillespie, C.J Burley, G.S Tillotson. (2004) Antimicrobial selection for community-acquired lower respiratory tract infections in the 21st century: a review of gemifloxacin. International Journal of Antimicrobial Agents 23:6, 533-546
CrossRef140
KRISTOFFER STRALIN, HANS HOLMBERG, PER OLCEN. (2004) Antibody response to the patient's own Haemophilus influenzae isolate can support the aetiology in lower respiratory tract infections. Brief report. APMIS 112:4-5, 299-303
CrossRef141
Sanjay Sethi. (2004) New developments in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease. Current Opinion in Infectious Diseases 17:2, 113-119
CrossRef142
Fernando J. Martinez. (2004) Acute bronchitis: State of the art diagnosis and therapy. Comprehensive Therapy 30:1, 55-69
CrossRef143
H Koch, H Landen, K Stauch. (2004) Daily-Practice Treatment of Acute Exacerbations of Chronic Bronchitis with Moxifloxacin in a Large Cohort in Germany. Clinical Drug Investigation 24:8, 449-455
CrossRef144
Anu Raghunathan, Nathan D. Price, Michael Y. Galperin, Kira S. Makarova, Samuel Purvine, Alex F. Picone, Tim Cherny, Tao Xie, Thomas J. Reilly, Robert Munson, Ryan E. Tyler, Brian J. Akerley, Arnold L. Smith, Bernhard O. Palsson, Eugene Kolker. (2004) In Silico Metabolic Model and Protein Expression of Haemophilus influenzae Strain Rd KW20 in Rich Medium. OMICS: A Journal of Integrative Biology 8:1, 25-41
CrossRef145
Sanjay Sethi. (2003) Gatifloxacin in community-acquired respiratory tract infection. Expert Opinion on Pharmacotherapy 4:10, 1847-1855
CrossRef146
Venkata Bandi, Marta Jakubowycz, Carla Kinyon, Edward O Mason, Robert L Atmar, Stephen B Greenberg, Timothy F Murphy. (2003) Infectious exacerbations of chronic obstructive pulmonary disease associated with respiratory viruses and non-typeable Haemophilus influenzae. FEMS Immunology & Medical Microbiology 37:1, 69-75
CrossRef147
Philippe Mojon, Jean Bourbeau. (2003) Respiratory infection: How important is oral health?. Current Opinion in Pulmonary Medicine 9:3, 166-170
CrossRef148
Timothy F. Murphy. (2003) Respiratory infections caused by non-typeable Haemophilus influenzae. Current Opinion in Infectious Diseases 16:2, 129-134
CrossRef149
Francisco J. Soto, Basil Varkey. (2003) Evidence-based approach to acute exacerbations of COPD. Current Opinion in Pulmonary Medicine 9:2, 117-124
CrossRef150
Richard S. Castaldo, Bartolome R. Celli, Fernando Gomez, Nicole LaVallee, Joseph Souhrada, John P. Hanrahan. (2003) A comparison of 5-day courses of dirithromycin and azithromycin in the treatment of acute exacerbations of chronic obstructive pulmonary disease. Clinical Therapeutics 25:2, 542-557
CrossRef151
Sanjay Sethi. (2003) The role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease. Current Infectious Disease Reports 5:1, 9-15
CrossRef152
(2002) New Strains of Bacteria and Exacerbations of COPD. New England Journal of Medicine 347:25, 2077-2079
Full Text153
Anthonisen, Nick R., . (2002) Bacteria and Exacerbations of Chronic Obstructive Pulmonary Disease. New England Journal of Medicine 347:7, 526-527
Full Text154
Timothy F. Murphy, Sanjay Sethi. (2002) Chronic Obstructive Pulmonary Disease. Drugs & Aging 19:10, 761-775
CrossRef
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