Treatment of Chlamydia pneumoniae infection in adult asthma: a before- after trial [see comments]

Hahn DL     

Antibiotics
Asthma
Chlamydia Infections
Chlamydia pneumoniae
Adolescence
Adult
Aged
Azithromycin
Child
Chronic Disease
Comparative Study
Doxycycline

Erythromycin
Female
Follow-Up Studies
Human
Male
Middle Age
Respiratory Function Tests
Support, Non-U.S. Gov't
Time Factors
Treatment Outcome
Clinical Trial

Abstract
BACKGROUND. Some diseases previously believed to be noninfectious, eg, peptic ulcer disease, are now known to be caused by chronic infection.  Recently, chronic Chlamydia pneumoniae infection has been suggested as a cause for adult-onset asthma.  The purpose of this study was to determine whether antichlamydial treatment would affect the natural history of this disease. 

METHODS. An open-label, before- after treatment trial was performed in a community-based, primary care office.  Forty-six patients (mean age 47.7 years; range 17 to 78) with moderate to moderately severe, stable, chronic asthma were treated a median of 4 weeks (range 3 to 9) with oral doxycycline (100 mg twice daily), azithromycin (1000 mg once weekly), or erythromycin (1000 mg daily).  Post-treatment pulmonary function and asthma symptoms were compared with baseline values.  Follow-up was an average of 6 months (range 1.5 to 36) post-treatment. 

RESULTS. Four patients with C pneumoniae respiratory tract infection developed chronic asthma, which disappeared after treatment in each case.  Of the remaining 42 seroreactive patients who were treated a mean of 6 years after the development of chronic asthma, one half had either complete remission or major clinical improvement (3 and 18 patients, respectively).  This improvement was significantly more likely to occur in patients with early disease (P = .01) and before the development of fixed obstruction (P < .01). 

CONCLUSIONS. Antimicrobial therapy appeared to "cure" or significantly improve asthma in approximately one half of treated adults, and the response pattern was consistent with chlamydial pathogenesis.  C pneumoniae infection in asthma may be clinically important and should be investigated further.

Dean Medical Center
Madison
Wisconsin
USA.

Detection of anti-Chlamydia pneumoniae IgE in children with reactive airway disease.

Emre U,      Sokolovskaya N,      Roblin PM,      Schachter J,      Hammerschlag MR     

Antibodies, Bacterial
Chlamydia pneumoniae
Chlamydia Infections
IgE
Adolescence
Asthma
Child
Child, Preschool
Comparative Study
Immunoblotting
Infant
Pneumonia

Abstract
An association of Chlamydia pneumoniae infection and reactive airway disease has been demonstrated in children.  To determine if C. pneumoniae infection triggers production of C. pneumoniae-specific IgE, sera were examined from 45 children with and without C. pneumoniae infection.  Anti-C. pneumoniae IgE was demonstrated by immunoblotting in 12 (85.7%) of 14 culture-positive asthmatic patients with wheezing compared with only 1 (9.1%) of 11 culture- positive patients with pneumonia, 2 (18.2%) of 11 culture-negative asthmatic children with wheezing, and 2 (22.2%) of 9 culture-negative asymptomatic patients.  The most commonly recognized proteins were at 98 (82.4%), 78 (58.8%), 58-60 (70.6%), and 36 kDa (64.7%).  The presence of anti-C. pneumoniae IgE by immunoblotting was not associated with the presence of anti-C. pneumoniae IgG and IgM by microimmunofluorescence.  These results suggest that production of specific IgE may be an underlying mechanism leading to reactive airway disease in some patients with C. pneumoniae infection.

Department of Pediatrics
State University of New York Health Science Center at Brooklyn 11203
USA.

Can acute Chlamydia pneumoniae respiratory tract infection initiate chronic asthma?

CLICK HERE TO VIEW FULL ARTICLE IN PDF FORMAT

Hahn DL,      McDonald R     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Respiratory Tract Infections
Acute Disease
Adolescence
Adult

Aged
Chronic Disease
Female
Human
Male
Middle Age
Respiratory Sounds

Abstract
BACKGROUND: Chlamydia pneumoniae infection can cause acute respiratory illnesses (including sinusitis, bronchitis, and pneumonia) that are sometimes associated with wheezing.  Little is known about whether acute infection in a previously unexposed, nonasthmatic individual can produce persistent wheezing leading to a diagnosis of chronic asthma. 

OBJECTIVE: We sought to determine whether patients with acute C. pneumoniae respiratory tract infections would develop chronic asthma. 

METHODS: A consecutive series of 163 primary care outpatient adolescents and adults (average age 43, 45% male) who had acute wheezing illnesses or chronic asthma were evaluated for C. pneumoniae infection by serologic testing.  A subgroup of these patients also had nasopharyngeal cultures for C. pneumoniae. 

RESULTS: Twenty patients (12%) were diagnosed with C. pneumoniae infection defined by serology (15), culture isolation (3), or both (2).  Of these 20, 10 patients wheezed for the first time and 6 of them subsequently developed chronic asthma (5) or chronic bronchitis (1) along with a serologic profile suggesting chronic infection.  The other 10 patients diagnosed with C. pneumoniae infection already had a diagnosis of chronic asthma.  In these patients initial serologic findings suggested chronic rather than acute infection. 

CONCLUSIONS: Acute C. pneumoniae respiratory tract infections in previously unexposed, nonasthmatic individuals can result in chronic asthma.  Patients previously diagnosed with chronic asthma should be evaluated for possible chronic C. pneumoniae infection

Dean Medical Center
Madison
Wisconsin
USA. dlhahn@facstaff.wisc.edu

Evidence for Chlamydia pneumoniae infection in steroid-dependent asthma.

CLICK HERE TO VIEW FULL ARTICLE IN PDF FORMAT

Hahn DL,      Bukstein D,      Luskin A,      Zeitz H     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Glucocorticoids, Synthetic
Administration, Inhalation
Adolescence
Aged
Antibiotics, Macrolide
Antibodies, Bacterial
Azithromycin

Case Report
Clarithromycin
Female
Human
Immunoglobulins
Male
Middle Age
Nebulizers and Vaporizers
Medline Database
Healthstar Database

Abstract
BACKGROUND: Chlamydia pneumoniae is an obligate intracellular respiratory pathogen capable of persistent infection.  Seroepidemiologic studies and the results of open-label antimicrobial treatment of patients with non-steroid-dependent asthma have suggested a potential role for C. pneumoniae in asthma. 

OBJECTIVE: To evaluate the results of antimicrobial treatment in patients with uncontrolled steroid-dependent asthma and serologic evidence suggesting C. pneumoniae infection. 

METHODS: Three nonsmoking asthmatic patients (aged 13 to 65 years) whose symptoms remained poorly controlled despite daily administration of inhaled and oral steroid (10 to 40 mg/d).  All met serologic criteria for current or recent C. pneumoniae infection. 

RESULTS: After prolonged treatment (6 to 16 weeks) with clarithromycin or azithromycin all three patients were able to discontinue oral steroids.  All three patients have remained well controlled with inhaled antiasthma therapy only during 3 to 24 months of postantibiotic therapy observation. 

CONCLUSIONS: In adolescent and adult asthmatic patients, Chlamydia pneumoniae infection may contribute to symptoms of asthma that are poorly controlled by steroids.  Serologic evidence for C. pneumoniae infection should be sought in such patients.  A trial of appropriate antibiotic therapy may be helpful in those patients with high titers of anti-C. pneumoniae IgG antibodies.

Dean Medical Center
Madison
Wisconsin
USA.

Asthma and chlamydial infection: a case series.

Hahn DL,      Golubjatnikov R     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Acute Disease
Adolescence
Adult
Aged
Bronchitis
Child
Comparative Study
Disease Outbreaks
Female

Human
Male
Middle Age
Mycoplasma pneumoniae
Pneumonia, Mycoplasma
Respiratory Sounds
Respiratory Tract Diseases
Support, Non-U.S. Gov't
Wisconsin
Medline Database
Healthstar Database

Abstract
BACKGROUND. Adult-onset asthma is frequently associated with antecedent respiratory symptoms that could represent either previously undiagnosed asthma or previous lung infections that result in subsequent asthma.  To further investigate a reported association of Chlamydia pneumoniae infection and adult reactive airway disease, we looked for evidence of atypical infections in patients with acute wheezing and nonwheezing respiratory illnesses. 

METHODS. Pharyngeal cultures and acute and convalescent serology for C pneumoniae and Mycoplasma pneumoniae were obtained from 131 primary care outpatients (mean age, 36 years) with acute wheezing or nonwheezing respiratory illnesses.  Peak flow measurements were obtained in patients with cough or wheeze.  Spirometry before and after bronchodilator use was obtained to substantiate the diagnosis of chronic asthma in patients who had persistent wheezing and dyspnea after enrollment. 

RESULTS. Twelve (9.2%) of 131 patients were classified as having chronic asthma, 5/12 developed chronic asthma for the first time during the study period.  Thirty (22.9%) patients were classified with acute asthmatic bronchitis, and 89 (67.9%) had nonwheezing illness.  Two of the newly diagnosed asthmatics met serologic criteria for acute C pneumoniae infection, and one had serologic evidence for acute M pneumoniae infection.  Compared with patients with nonwheezing respiratory illnesses, C pneumoniae seroreactivity was significantly (P < .001) associated with both chronic asthma and with acute asthmatic bronchitis. 

CONCLUSIONS.Acute wheezing illness was encountered frequently in this primary care setting.  Although most acute wheezing respiratory illness resolved without obvious chronic sequelae, some patients had persistent symptoms and were diagnosed with chronic asthma.  C pneumoniae seroreactivity was associated with both acute and chronic wheezing, suggesting that pulmonary infection with this intracellular pathogen plays a role in the natural history of reactive airway disease.

Arcand Park Clinic
Division of Dean Medical Center
Madison
WI 53704.

Association of Chlamydia pneumoniae (strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma [see comments]

Hahn DL,      Dodge RW,      Golubjatnikov R     

Asthma
Bronchitis
Chlamydia
Chlamydia Infections
Respiratory Sounds
Respiratory Tract Infections
Adolescence
Adult
Aged
Antibodies, Bacterial
Child

Chronic Disease
Comparative Study
Female
Human
Male
Middle Age
Prospective Studies
Recurrence
Retrospective Studies
Support, Non-U.S. Gov't

Abstract
OBJECTIVE-- To study the clinical characteristics of respiratory tract illness caused by Chlamydia pneumoniae.  DESIGN.-Prospective clinical, bacteriologic, and serologic study.  Secondarily, a matched comparison of patients with and without evidence of C pneumoniae infection (serologic titers greater than or equal to 1:64 and less than 1:16, respectively). 

SETTING.-- Four primary care (family practice) clinics in Madison, Wis, and nearby towns. 

PATIENTS.-- The study included 365 white males and females (mean age, 34.2 years). 

MAIN OUTCOME MEASURES.-- Association of acute C pneumoniae infection with signs and symptoms of respiratory illness and the relationship of C pneumoniae antibody titer with wheezing at the time of enrollment in the study, and with the diagnosis of asthmatic bronchitis. 

RESULTS.-- Nine (47%) of 19 patients with acute C pneumoniae infection had bronchospasm during respiratory illness, and there was a strong quantitative association of C pneumoniae titer with wheezing at the time of enrollment in the study (P = .01).  In the matched study, C pneumoniae antibody was significantly associated with asthmatic bronchitis after, but not before, respiratory illness (odds ratio, 7.2; 95% confidence interval, 2.2 to 23.4).  Four infected patients had newly diagnosed asthma after illness, and four others had exacerbation of previously diagnosed asthma.  There was no serologic evidence of coexisting Mycoplasma pneumoniae, Chlamydia trachomatis, or respiratory viral infection in 96% of patients with asthmatic bronchitis and asthma. 

CONCLUSIONS.-- Some C pneumoniae antibody titers, although not diagnostic of chlamydial infection by present criteria, probably represent acute reinfection or ongoing chronic infection.  Repeated or prolonged exposure to C pneumoniae may have a causal association with wheezing, asthmatic bronchitis, and asthma.

Arcand Park Clinic
Division of Dean Medical Center
University of Wisconsin
Madison 53704.

Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae.

Antibiotics, Macrolide
Asthma
Chlamydophila Infections
Chlamydophila pneumoniae
Pneumonia, Bacterial
Roxithromycin
Adult
Antibodies, Bacterial
Chronic Disease
Double-Blind Method
Female
Follow-Up Studies
Forced Expiratory Volume

Human
IgG
Male
Middle Age
Peak Expiratory Flow Rate
Severity of Illness Index
Support, Non-U.S. Gov't
Time Factors
Treatment Outcome
Clinical Trial
Multicenter Study
Randomized Controlled Trial

Abstract
An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control.  We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16.  A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo.  At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02).  With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS).  In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04).  At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant.  Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained.  Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.
Comment in: Am J Respir Crit Care Med. 2001 Aug 15;164(4):513-4

Auckland Hospital
Auckland
New Zealand. pn.black@auckland.ac.nz

 Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma.

Gencay M,      Rudiger JJ,      Tamm M,      Soler M,      Perruchoud AP,      Roth M     

Antibodies, Bacterial
Asthma
Chlamydophila Infections
Chlamydophila pneumoniae
Adult
Aged
Case-Control Studies
Chronic Disease

Female
Fluorescent Antibody Technique
Human
IgA
IgG
Male
Middle Age
Support, Non-U.S. Gov't

Abstract
The worldwide increase in asthma incidences and the impact of the disease on public health care have led to new investigations of the cause of the disease.  Besides well-defined environmental causes, accumulating evidence suggests that respiratory tract infections play an important role in the pathogenesis of asthma.  Among these microorganisms Chlamydia pneumoniae is an intracellular pathogen causing persistent infection.  Chlamydia pneumoniae infection has been discussed as possibly inducing the development of asthma.  This study was designed to investigate the presence of C. pneumoniae-specific IgG, IgA, and IgM antibodies in serum samples of 33 adults with a clinical history of asthma, positive methacholine test, and reduced FEV(1).  Patients with asthma were compared with age-, sex-, and locality-matched control subjects (n = 33).  We observed no acute infection either in patients with asthma or in control subjects, but 63% of all investigated individuals had signs of past infection.  Chlamydia pneumoniae-specific IgA was detected in 52% of the patients with asthma and in 15% of the healthy control subjects (p < 0.01).  Serological evidence of chronic infection with C. pneumoniae (high IgG [> pr = 1:512] and high IgA [> or = 1:40]) was more frequent in patients with asthma (18.2%) compared with control subjects (3.0%) (p < 0.01).  Our results provide further evidence that chronic infection with C. pneumoniae is linked to asthma.

Department of Virology
Haartman Institute
University of Helsinki
Helsinki
Finland.

Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection.

ten Brinke A,      van Dissel JT,      Sterk PJ,      Zwinderman AH,      Rabe KF,      Bel EH     

Asthma
Chlamydophila Infections
Chlamydophila pneumoniae
Hypersensitivity, Immediate
Lung
Adolescence
Adult
Aged
Antibodies, Bacterial

Cross-Sectional Studies
Female
Forced Expiratory Volume
Human
IgA
IgG
Male
Middle Age
Support, Non-U.S. Gov't

Abstract
 BACKGROUND: Persistent airflow limitation may develop in patients with asthma, particularly in adults with nonatopic (intrinsic) disease.  Although the underlying mechanisms are still unknown, respiratory infections might be involved. 

OBJECTIVE: We investigated the annual loss of lung function in relation to seropositivity to Chlamydia pneumoniae in different subgroups of patients with severe asthma according to age at onset of asthma and atopic status. 

METHODS: One hundred one nonsmoking outpatients with a pulmonologist's diagnosis of severe asthma (32 men and 69 women; mean age, 46.0 years; range, 18-75 years) were included in a cross- sectional study.  C pneumoniae-specific serum IgG and IgA were measured by means of ELISA.  The estimated decline in lung function was calculated from the relationship between postbronchodilator FEV(1)/vital capacity (percent predicted) and the duration of asthma and expressed as the slope of the regression line. 

RESULTS: Patients with adult-onset nonatopic asthma and positive IgG antibodies to C pneumoniae had a significantly steeper slope of the regression line compared with the other subgroups of asthmatic patients (P =.001), being indicative of a 4-fold greater estimated decline in postbronchodilator FEV(1)/vital capacity (2.3% vs 0.5% predicted per year of asthma duration). 

CONCLUSION: These results suggest that C pneumoniae infection might promote the development of persistent airflow limitation in patients with nonatopic adult-onset asthma.  It remains to be established whether viable pathogens that are accessible for therapeutic intervention are still present in the lower airways.

Department of Pulmonary Diseases
Leiden University Medical Center
Leiden
The Netherlands.

Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma [published erratum appears in Am J Respir Crit Care Med 1998 Nov;158(5 Pt 1):1692]

Kraft M,      Cassell GH,      Henson JE,      Watson H,      Williamson J,      Marmion BP      Gaydos CA,      Martin RJ     

Asthma
Bronchi
Mycoplasma pneumoniae
Adult
Biopsy
Bronchoalveolar Lavage Fluid
Chlamydia Infections
Chlamydia pneumoniae
Chronic Disease
Female
Human
Influenza
Influenza A Virus, Human
Influenza B Virus

Male
Mycoplasma
Mycoplasma fermentans
Parainfluenza Virus 1, Human
Parainfluenza Virus 2, Human
Parainfluenza Virus 3, Human
Paramyxovirus Infections
Pneumonia, Mycoplasma
Respiratory Syncytial Virus Infections
Respiratory Syncytial Viruses
Rubulavirus Infections
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.

Abstract
Infection with Mycoplasma pneumoniae has been shown to exacerbate asthma in humans.  However, the role of M. pneumoniae in the pathogenesis of chronic asthma has not been defined.  Eighteen asthmatics with chronic, stable asthma and 11 nonasthmatic control subjects underwent evaluation of the upper and lower airways and serologic analysis to determine the presence of M. pneumoniae, Chlamydia pneumoniae, and seven respiratory viruses through culture, enzyme-linked immunoassay (EIA) and polymerase chain reaction (PCR).  M. pneumoniae was detected by PCR in 10 of 18 asthmatics and one of 11 control subjects (p = 0.02).  In nine of the 10 patients, the organism was detected in bronchoalveolar lavage or bronchial biopsies.  Seven of 18 asthmatics and one of 11 control subjects were also positive for M. fermentans and M. genitalium by PCR.  All patients' cultures, EIAs, and serology were negative for M. pneumoniae.  All PCR and cultures were negative for C. pneumoniae, and all EIAs for respiratory viruses were negative in all subjects.  Nine asthmatics and one control subject exhibited positive serology for C. pneumoniae (p = 0.05).  M. pneumoniae was present in the lower airways of chronic, stable asthmatics with greater frequency than control subjects, and may play a role in the pathogenesis of chronic asthma.

Department of Medicine
National Jewish Medical and Research Center and the University of Colorado Health Sciences Center
Denver
Colorado
USA.

The association of Chlamydia pneumoniae infection and reactive airway disease in children [see comments]

Emre U,      Roblin PM,      Gelling M,      Dumornay W,      Rao M,      Hammerschlag MR      Schachter J     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Adolescence
Case-Control Studies
Child

Child, Preschool
Female
Human
Male
Prospective Studies
Support, Non-U.S. Gov't

Abstract
OBJECTIVE: To determine the possible association of Chlamydia pneumoniae infection and reactive airway disease in children. 

DESIGN: Prospective observational study. 

SETTING: Pediatric emergency department in Children's Medical Center of Brooklyn (NY), Kings County Hospital Center. 

PARTICIPANTS: One hundred eighteen children with acute episodes of wheezing and 41 age- and sex-matched healthy controls, aged 5 to 16 years. 

INTERVENTIONS: Children with cultures positive for C pneumoniae were treated with antibiotics. 

MEASUREMENTS/MAIN RESULTS: Cultures for C pneumoniae and serum samples for antibody testing were obtained from subjects and healthy controls.  We isolated C pneumoniae from 13 (11%) children with wheezing and from two (4.9%) controls.  Seven (58.3%) of 12 children with positive cultures had no detectable antibody to C pneumoniae and only three (25%) children had serologic evidence of acute infection.  Six children had positive cultures on multiple occasions, ranging from 1 to 5 months.  The children with wheezing were treated with erythromycin or clarithromycin, a new macrolide antibiotic approved for use in adults; all eventually had a negative culture.  Nine (75%) of these children demonstrated clinical and laboratory improvement of the reactive airway disease after the eradication of chlamydial infection. 

CONCLUSIONS: Infection with C pneumoniae can trigger acute episodes of wheezing in children with asthma.  Treatment of C pneumoniae infection may improve the course of reactive airway disease in these patients.

Comment in: Arch Pediatr Adolesc Med 1995 Feb;149(2):219-21
Comment in: Arch Pediatr Adolesc Med 1995 Mar;149(3):341-2

Serologic markers for Chlamydia pneumoniae in asthma.

Hahn DL,      Peeling RW,      Dillon E,      McDonald R,      Saikku P     

Asthma
Biological Markers
Chlamydia pneumoniae
Chlamydia Infections
Adult
Antibodies, Anti-Idiotypic
Antibodies, Bacterial
Bronchitis

Chaperonin 60
Female
Human
Male
Middle Age
Serologic Tests
Support, Non-U.S. Gov't

Abstract
BACKGROUND: Chlamydia pneumoniae infection has been reported as a possible etiologic agent in asthma, which in primary care settings often appears to be initiated by acute respiratory infections. 

OBJECTIVE: To determine if serologic markers for C. pneumoniae are associated with adult asthma that first became symptomatic after an acute respiratory illness (asthma associated with infection:

AAWI).

METHODS: Serum samples from 164 primary care outpatients, mean age 44 years, (68 with AAWI; 36 with atopic, occupational or exercise- induced asthma (non-AAWI); 16 nonasthmatic patients with acute bronchitis; and 44 asymptomatic nonasthmatic controls) were tested for the presence of C. pneumoniae-specific IgG and IgA antibodies.  Levels of chlamydial heat shock protein 60 (CHSP60) antibody were also measured.  Those positive for CHSP60 were tested for C. pneumoniae-specific IgE antibodies by immunoblotting.     

RESULTS: Statistically significant differences in IgG and IgA seroreactivity were noted between groups: acute bronchitis and AAWI had the highest levels (93% to 94% IgG seroreactivity, 69% to 75% IgA seroreactivity) whereas non-AAWI and asymptomatic controls had the lowest levels (61% to 84% IgG seroreactivity, 31% to 43% IgA seroreactivity, P < .02 after adjustment for age, sex and smoking).  CHSP60 antibodies were significantly more prevalent in AAWI than in non-AAWI (19% versus 3%, P = .02).  IgE antibodies against C. pneumoniae 60, 62, and/or 70 kD antigens were detected in 5 of 13 CHSP60 positive AAWI patients.  Persistent IgG, IgA, and CHSP60 seroreactivities were noted in all seropositive asthma patients with serial serum samples. 

CONCLUSIONS: Serologic markers of C. pneumoniae infection were associated with acute bronchitis and with asthma that first became symptomatic following respiratory illness.  Serologic responses to C. pneumoniae may be useful in the classification and diagnosis of asthma.

Dean Medical Center
Madison
Wisconsin
USA.

Chlamydia pneumoniae, asthma, and COPD: what is the evidence?

Hahn DL     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Lung Diseases, Obstructive
Respiratory Tract Infections
Acute Disease
Adolescence
Adult
Animal
Antibodies, Bacterial
Biological Markers
Case-Control Studies
Cell Movement
Child

Chronic Disease
Comorbidity
Disease Progression
DNA, Bacterial
Human
Macrophages, Alveolar
Mice
Pneumonia, Bacterial
Serologic Tests
Support, Non-U.S. Gov't
Virus Diseases
Review
Review Of Reported Cases
Review, Tutorial

Abstract

LEARNING OBJECTIVES: Reading this article will familiarize the reader with (1) the unique chlamydial intracellular life cycle and the propensity for human chlamydial infections to become persistent and to result in immunopathologic (inflammatory) damage in target organs and (2) current evidence linking Chlamydia pneumoniae (Cpn) infection to obstructive lung diseases (asthma and chronic obstructive pulmonary disease, COPD).  Potential therapeutic implications of the Cpn-asthma association are also discussed. 

DATA SOURCES: All Medline articles (January 1985 to March 1999) that cross-referenced the exploded MESH headings "lung diseases, obstructive" and "Chlamydia pneumoniae" (N = 76).  Additional referenced articles, published abstracts, book chapters, and conference proceedings were also utilized.  STUDY SELECTION: (1) Case reports and case series that identified Cpn infection in asthma and/or COPD and (2) epidemiologic studies of markers for Cpn infection in asthma and/or COPD that included one or more control groups. 

RESULTS: Of 18 controlled epidemiologic studies (over 4000 cases/controls), 15 found significant associations between Cpn infection and asthma using organism detection (polymerase chain reaction (PCR) testing (n = 2 studies) or fluorescent antigen testing (n = 1)), Cpn-specific secretory IgA (sIgA) antibody testing (n = 1), and/or specific serum IgE (n = 2), IgA (n = 4), IgG (n = 3) or other antibody criteria (n = 7).  Eight case reports and 13 case series of Cpn infection in asthma (over 100 patients) also include descriptions of improvement or complete disappearance of asthma symptoms after prolonged antibiotic therapy directed against Cpn.  Significant associations with COPD (over 1000 cases/controls) were reported in 5 of 6 studies.  Results of treating chronic chlamydial infections in COPD patients have not been reported. 

CONCLUSIONS: Although the full clinical significance of these Cpn-obstructive lung disease associations remains to be established, reports of asthma improvement after treatment of Cpn infection deserve further investigation.  Clinicians who manage asthma should be aware of this information since it may help to manage difficult cases.  The hypothesis that Cpn infection in COPD can amplify smoking-associated inflammation and worsen fixed obstruction also deserves further study.

Dean Medical Center
Madison
Wisconsin 53704
USA.

Comparison of two serological methods and a polymerase chain reaction- enzyme immunoassay for the diagnosis of acute respiratory infections with Chlamydia pneumoniae in adults.

Petitjean J,      Vincent F,      Fretigny M,      Vabret A,      Poveda JD,      Brun J,      Freymuth F     

Chlamydia pneumoniae
Chlamydia Infections
Respiratory Tract Infections
Acute Disease
Adult
Aged
Aged, 80 and over
Antibodies, Bacterial
Asthma
Bronchi
Bronchoalveolar Lavage Fluid
Community-Acquired Infections
Comparative Study

DNA, Bacterial
Enzyme-Linked Immunosorbent Assay
Female
Fluorescent Antibody Technique, Direct
Human
Immunoenzyme Techniques
Male
Middle Age
Nasopharynx
Pneumonia, Bacterial
Polymerase Chain Reaction
Prospective Studies
Sensitivity and Specificity

Abstract
Chlamydia pneumoniae is a common respiratory tract pathogen.  Serological methods currently used for the diagnosis of C. pneumoniae infection lack specificity, give ambiguous results from a single serum sample and often provide only a retrospective diagnosis.  A prospective study was undertaken to assess whether PCR could be a useful addition to the serological techniques routinely practised for diagnosis.  This study investigated 68 adult patients with a diagnosis of acute respiratory infection.  Acute and convalescent serological determination of antibodies to C. pneumoniae were performed by means of an rELISA test and a micro-immunofluorescence (MIF) test.  Nasopharyngeal aspirates or bronchoalveolar lavage specimens and bronchial aspirates obtained from the 68 patients were evaluated by PCR-enzyme immunoassay (PCR-EIA) for the presence of C. pneumoniae and by immunofluorescence assay and cell culture for virus identification.  Mycoplasma pneumoniae serology was also performed.  Eight patients (11.8%) were positive by either rELISA or PCR-EIA, or both, with an infection rate of 5 (18.5%) of 27 in patients with community-acquired pneumonia, 2 (9%) of 22 in asthmatic patients and 1 (5%) of 19 in patients with an exacerbation of chronic obstructive pulmonary disease.  Serological evidence of acute infection was found in four of these patients with the rELISA test and in three others with the MIF test.  PCR-EIA detected C. pneumoniae DNA in four specimens, but there were concordant results with both rELISA and PCR- EIA in only one patient A positive PCR-EIA was also obtained in a patient who did not show an antibody response in acute serum.  The discrepancy between serological and PCR-EIA results reflects the difficulties in routine laboratory diagnosis of C. pneumoniae infection and the necessity for further studies with optimised techniques.

Laboratory of Human and Molecular Virology
CHRU Caen
France.

Chlamydia pneumoniae and exacerbations of asthma in adults.

Miyashita N,      Kubota Y,      Nakajima M,      Niki Y,      Kawane H,      Matsushima T     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Acute Disease
Adolescence

Adult
Aged
Aged, 80 and over
Antibodies, Bacterial
Female

Human
Male
Middle Age

Abstract
BACKGROUND: Chlamydia pneumoniae is a frequent causative agent of acute respiratory disease and has been recently reported as a possible cause of asthma. 

OBJECTIVE: We assessed the prevalence of C. pneumoniae infections in adult patients with acute exacerbations of asthma. 

METHODS: One hundred sixty-eight adult patients with acute exacerbations of asthma and 108 control subjects matched for age, sex, and smoking status were studied.  Nasopharyngeal swab specimens were obtained from all subjects and analyzed by isolation in cell culture and polymerase chain reaction (PCR) test for C. pneumoniae.  Serum samples were also obtained and tested for C. pneumoniae- specific antibodies by the microimmunofluorescence test. 

RESULTS: C. pneumoniae was isolated from two (1.2%) asthma patients and none from controls and detected by PCR from nine (5.4%) cases and one (0.9%) control.  Both culture positive specimens were also positive in PCR.  Further, serologic evidence of acute C. pneumoniae infection was present in 15 (8.9%) of asthma patients and in three (2.8%) of controls (P = .048).  The prevalence of C. pneumoniae-specific IgG and IgA was significantly higher in asthma cases than in controls (IgG > or = 1:16: 85.1% versus 67.6%, P = .001; IgA > or = 1:16: 47.6% versus 16.7%, P < .001).  Mean titer of IgG and IgA was also significantly greater in asthma cases than in controls (IgG: 38.8 versus 18.1, P = .0001; IgA: 17.2 versus 6.1, P = .0001). 

CONCLUSIONS: Our data suggest that C. pneumoniae infection may trigger acute exacerbations of adult asthma.

Department of Medicine
Kawasaki Medical School
Kurashiki City
Okayama
Japan.

Association of Chlamydia pneumoniae IgA antibodies with recently symptomatic asthma.

Hahn DL,      Anttila T,      Saikku P     

Antibodies, Viral
Asthma
Chlamydia pneumoniae
Chlamydia Infections
Adult
Aged
Aged, 80 and over
Case-Control Studies

Female
Human
IgA
Male
Middle Age
Support, Non-U.S. Gov't
Medline Database
Healthstar Database

Abstract
To determine whether recently diagnosed adult-onset asthma is associated with serologic evidence of chronic Chlamydia pneumoniae infection, we performed a case-control study in a primary care clinic of cases with asthma (25 adults reporting first symptoms of asthma within 2 years of enrollment) and 45 concurrently enrolled sex and age (+/- 10 years) matched non-asthmatic controls with normal pulmonary function.  C. pneumoniae-specific IgA, IgG and IgG4 antibodies, and circulating immune complexes (CIC) were measured by microimmunofluorescence testing.  Results showed that frequencies of IgG titres > or = 16 (92%), IgG4 titres > or = 16 (20%) and CIC > or = 4 (60%) in asthma patients were not significantly different from those of controls.  However, asthmatics had a significantly higher prevalence of C. pneumoniae-specific IgA titres > or = 10 (72% of cases vs 44% of controls, P < 0.05).  After adjustment for the effects of age, sex and smoking, the odds ratio for an association of IgA and asthma was 3.7 (95% confidence interval 1.2-11.5).  We conclude that recently symptomatic reversible airway obstruction in adults is associated with the presence of C. pneumoniae-specific IgA antibodies, a proposed indicator of chronic respiratory C. pneumoniae infection.

Dean Medical Center
Madison
Wisconsin
USA.

Host immune response to Chlamydia pneumoniae heat shock protein 60 is associated with asthma.

Huittinen T,      Hahn D,      Anttila T,      Wahlstrom E,      Saikku P,      Leinonen M     

Abstract
Chlamydia pneumoniae infection has been associated with asthma.  It has also been suggested that heat shock protein 60 (Hsp60) belonging to a class of highly conserved proteins may play a role in the pathogenesis of chlamydial infections.  The purpose was to study whether the host immune response to C. pneumoniae Hsp60 is associated with asthma and decreased pulmonary function.  An enzyme immunoassay was used to measure immunoglobulin-(Ig)A and IgG antibodies against recombinant C. pneumoniae Hsp60 and human Hsp60 in a study group consisting of 24 cases of recently symptomatic asthma and 62 nonasthmatic controls.  A strong (r=0.50) and significant (p<0.001) correlation was observed between C.pneumoniae and human Hsp60 IgA antibodies, but only C. pneumoniae Hsp60 IgA antibodies were significantly associated with asthma (p = 0.02).  Pulmonary function, as measured by forced expiratory volume in one second, also inversely correlated (r = -0.23, p = 0.04) with the quantity of C. pneumoniae Hsp60 IgA antibodies, suggesting an association with the severity of pulmonary obstruction.  By showing an association of Chlamydia pneumoniae heat shock protein 60 immunoglobulin A antibodies with asthma, the results support the hypothesis of an association between Chlamydia pneumoniae infection and asthma and support the need for further investigations on the role of heat shock protein 60 in the pathogenesis of asthma.

National Public Health Institute
Oulu
Finland.

Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing.

Esposito S,      Blasi F,      Arosio C,      Fioravanti L,      Fagetti L,      Droghetti R      Tarsia P,      Allegra L,      Principi N     

Abstract
In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae in reactive airway disease, 71 children aged 2-14 yrs with an acute episode of wheezing and 80 age-matched healthy children were studied.  Sera for the determination of specific antibody levels and nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae deoxyribonucleic acid were obtained on admission and after 4-6 weeks.  All children with wheezing received a standard therapy with inhaled corticosteroids and bronchodilators for 5-7 days; when antibiotic was added on the basis of the judgement of the paediatrician in charge, clarithromycin 15 mg.kg body weight(-1).day(- 1) for 10 days was used.  Acute M. pneumoniae and C. pneumoniae infections were detected significantly more often in children with wheezing than in controls.  In patients infected with one of the two pathogens, a history of recurrent wheezing was significantly more frequent than in those without either infection.  During a 3-month follow-up period, among nonantibiotic-treated children, those with acute M. pneumoniae and/or C. pneumoniae infection showed a significantly higher recurrence of wheezing than those without acute M. pneumoniae and/or C. pneumoniae infection (p=0.03).  These results highlight the apparently significant relationship of Mycoplasma pneumoniae and Chlamydia pneumoniae with wheezing in children, particularly in subjects with a history of recurrent episodes, and the possible improvement in the course of reactive airway disease within paediatric patients with acute Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection.

Paediatric Dept I
University of Milan
Italy.

[Chronic Chlamydia pneumoniae infection in patients with asthma] Przewlekle zakazenie Chlamydia pneumoniae u chorych na astme oskrzelowa.

Niedzwiadek J,      Mazur E,      Chmielewska-Badora J,      Gryglicka B      Wegrzyn-Szkutnik I,      Chabros B,      Koziol-Montewka M,      Milanowski J     

Asthma
Chlamydia Infections
Chlamydophila pneumoniae
Adult
Aged
Case-Control Studies
Chronic Disease

Comorbidity
Human
IgA
IgG
IgM
Middle Age
Serologic Tests

Published in Polish

Abstract
The aim of our study was to evaluate the frequency of Chlamydia pneumoniae infection (especially chronic infection) in 41 asthma patients.  They have been assigned to 3 groups, according to disease severity.  Control group consisted of 35 age matched healthy volunteers (without cardiac and pulmonary diseases).  The levels of specific IgG, IgA and IgM in patients' serum have been estimated using indirect microimmunofluorescence.  According to serologic criteria, 23(56.1%) asthma patients and 4(11.4%) healthy controls have appeared to be chronically infected with Chlamydia pneumoniae (p < 0.001).  Acute Chlamydia pneumoniae infection was present in 3(7.3%) asthma patients and in 2(5.7%) healthy controls.  Taking in account asthma severity, persistent Chlamydia pneumoniae infection has occurred more frequently in patients with moderate and severe asthma than in ones with mild asthma.  Acute Chlamydia pneumoniae infection was present in 9.1% and 12.5% of patients with mild and severe asthma respectively.

Katedra i Zaklad Mikrobiologii Lekarskiej AM w Lublinie.

[Impact of Chlamydia pneumoniae infections on asthma] Impact des infections a Chlamydia pneumoniae sur la maladie asthmatique.

Asthma
Chlamydophila Infections
Chlamydophila pneumoniae
Adult
Age Factors
Antibiotics
Child

Comparative Study
Human
Microbiological Techniques
Middle Age
Time Factors
Review
Review, Tutorial

Published in French

Abstract
VIRUSES AND BACTERIA: The fact that the airways are exposed to a large number of infectious agents could explain the frequency of respiratory infections and their causal effect in bronchial inflammation.  Viruses are most often the causal agent, but the frequency of bacterial infections make them potential candidates in certain respiratory diseases.  Chlamydia are particularly important due to their capacity to provoke immune dysfunction and chronic inflammation. 

EFFECT ON ASTHMA: It is not surprising to find biological evidence of Chlamydia pneumoniae infection in a large number of subjects who experience major degradation of their asthma because asthmatic subjects are particularly susceptible to respiratory infections and Chlamydia pneumoniae is a frequent cause of such infections. 

PATHOGENIC EFFECT: Finding Chlamydia pneumoniae as the causal agent in asthma is however much more surprising, with a much different consequence.  There are however many epidemiological and clinical findings and case observations (Chlamydia pneumoniae asthma associations, prolonged favorable course in certain obstructive bronchial diseases after a short antibiotic regimen) as well as provocative pathophysiological data favoring this particular form of "infectious asthma". 

Service de Pneumologie et de Reanimation respiratoire (Pr Fournier)
Hopital Beaujon
Clichy.

Chlamydia pneumoniae infection in patients with acute bronchitis and bronchial asthma

Abstract
In this study, a total of 60 patients with acute bronchitis, 71 patients with bronchial asthma and 20 healthy volunteers were serologically and bacteriologically analyzed to investigate whether Chlamydia pneumoniae infection is associated with the onset and the exacerbation with acute bronchitis and bronchial asthma.  Antibody titers to Chlamydia pneumoniae were also measured and compared by ELISA method.  The antibody-positive rate in the patients with acute bronchitis (88.4%) was significantly higher than that in the patients with bronchial asthma (73.3%) or that in the healthy volunteers (60%).  And the levels of the IgA antibody in the patients with acute bronchitis were significantly higher than those in the patients with bronchial asthma or those in the healthy volunteers.  The rate of acute C. pneumoniae infection in the patients with acute bronchitis (20%) did not show significantly differences compared with that in the patients with bronchial asthma (15.5%) or that in the healthy volunteers (10%).  The cases of acute C. pneumoniae infection had both as a single etiologic agent and as a mixed infection, most often with Streptococcus pneumoniae.  Therefore, we demonstrated that the acute C. pneumoniae infection may be associated with the onset and the exacerbation in acute bronchitis and bronchial asthma.

Department of Pulmonary Medicine
Hiroshima Prefectural Hospital.

Chlamydia pneumoniae serological status is not associated with asthma in children or young adults.

Mills GD,      Lindeman JA,      Fawcett JP,      Herbison GP,      Sears MR     

Antibodies, Bacterial
Asthma
Chlamydia pneumoniae
Chlamydia Infections
Adolescence
Adult
Bronchial Provocation Tests
Case-Control Studies
Child
Child, Preschool
Comparative Study
Diagnosis, Differential

Female
Fluorescent Antibody Technique
Human
IgA
IgG
Male
Prevalence
Prospective Studies
Risk Factors
Support, Non-U.S. Gov't
Medline Database
Healthstar Database

Abstract
BACKGROUND: The factors that cause the allergic sensitization and inflammation in asthma still remain to be clarified.  A role for Chlamydia pneumoniae has been suggested although serological studies have produced conflicting findings.  This study aims to clarify the relationship between asthmatic variables and C. pneumoniae serological status. 

METHODS: A case-control study was undertaken on an asthma-enriched subset from a longitudinal birth cohort.  In all, 198 subjects (96 with self-reported asthma) had C. pneumoniae serology (microimmunofluorescence [MIF] IgG, IgA) undertaken at age 11 and age 21 and assessment made in relation to a number of asthma variables. 

RESULTS: The only statistically significant finding was in subjects self-reporting asthma at age 21 who had evidence of lower IgG titres (P = 0.046), a finding in the opposite direction to that expected from the hypothesis.  Subjects with high IgG titres (> or =128) were less likely to have reported ever having asthma; odds ratio (OR) = 0.29, (95% CI: 0.10-0.87).  No association existed between symptoms suggestive of asthma in the previous 12 months and either IgG (P = 0.127) or IgA (P = 0.189) antibody titres at age 21.  Likewise, no association was found between symptoms suggestive of asthma in the previous two years and C. pneumoniae IgG antibody titre (P = 0.81) at age 11.  There was no evidence of an association with any of the other variables examined at either age 11 or age 21.  These included use of inhaled steroids, serum IgE levels, airway responsiveness, skin test evidence of atopy, or smoking status. 

CONCLUSION: The results of this study suggest that C. pneumoniae infection when diagnosed by MIF serology is not a major risk factor for the development of asthma in children and young adults.  The study has not, however, addressed the role this organism may play in specific asthmatic subsets or asthma exacerbations.

Waikato Academic Division
School of Medicine
University of Auckland
Hamilton
New Zealand. millsg@hwl.co.nz

Production of basic fibroblast growth factor and interleukin 6 by human smooth muscle cells following infection with Chlamydia pneumoniae.

Rodel J,      Woytas M,      Groh A,      Schmidt KH,      Hartmann M,      Lehmann M,      Straube E     

Chlamydia pneumoniae
Fibroblast Growth Factor, Basic
Interleukin-6
Muscle, Smooth
Asthma
Atherosclerosis
Bronchi
Chlamydia trachomatis

Comparative Study
Immunoassay
Platelet-Derived Growth Factor
Species Specificity
Support, Non-U.S. Gov't
Medline Database
Cancerlit Database

Abstract
Chlamydia pneumoniae infection has been associated with asthma and atherosclerosis.  Smooth muscle cells represent host cells for chlamydiae during chronic infection.  In this study we demonstrated that C. pneumoniae infection of human smooth muscle cells in vitro increased production of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) as shown by reverse transcription-PCR, immunoblotting, and enzyme-linked immunosorbent assay.  In contrast, levels of platelet-derived growth factor A-chain mRNA were not affected after infection.  The stimulation of bFGF and IL-6 production was most effective when viable chlamydiae were used as inoculum.  Furthermore, inhibition of bacterial protein synthesis with chloramphenicol prevented up-regulation of IL-6 and bFGF in infected cells.  Addition of IL-6 antibody to infected cultures diminished bFGF expression, indicating involvement of produced IL-6.  These findings suggest that chlamydial infection of smooth muscle cells elicits a cytokine response that may contribute to structural remodeling of the airway wall in chronic asthma and to fibrous plaque formation in atherosclerosis.

Institute of Medical Microbiology
Friedrich Schiller University of Jena
D-07740 Jena
Germany. Roedel@bach.med.uni-jena.de

The role of atypical organisms in asthma.

Daian CM,      Wolff AH,      Bielory L     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Mycoplasma pneumoniae
Opportunistic Infections
Pneumonia, Mycoplasma
Adolescence
Adult
Aged
Aged, 80 and over
Child
Child, Preschool

Female
Human
Male
Middle Age
Prognosis
Randomized Controlled Trials
Risk Assessment
Review
Review, Tutorial
Medline Database
Healthstar Database

Abstract
Atypical organisms (Chlamydia pneumoniae, Mycoplasma pneumoniae) have been recently linked to asthma in various ways: an infection with these organisms may precede asthma onset, exacerbate asthma, or make asthma control more difficult.  Their ability to elicit a TH2 response and promote airway inflammation may be the common pathway in the development of an atopic inflammatory response.  This article presents a summary of the evidence that infection with Chlamydia pneumoniae or Mycoplasma pneumoniae may play a significance role in asthma.

UMDNJ-New Jersey Medical School
Newark
USA.

Serological evidence of infection with Chlamydia pneumoniae is related to the severity of asthma.

Black PN,      Scicchitano R,      Jenkins CR,      Blasi F,      Allegra L,      Wlodarczyk J      Cooper BC     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Administration, Inhalation
Adult
Beclomethasone
Double-Blind Method
Female
Glucocorticoids, Synthetic
Human
IgA

IgG
Logistic Models
Male
Severity of Illness Index
Support, Non-U.S. Gov't
Clinical Trial
Multicenter Study
Randomized Controlled Trial
Medline Database
Healthstar Database

Abstract
There is evidence that infection with Chlamydia pneumoniae is associated with asthma of recent onset and that it can influence the severity of asthma.  This has led to the suggestion that macrolide antibiotics may be useful in the treatment of asthma in subjects infected with C. pneumoniae.  This study examined the association between immunoglobulin (Ig)G and IgA titres to C. pneumoniae and the severity of asthma.  IgG and IgA antibodies to C. pneumoniae were measured in 619 subjects with asthma (18-60 yrs), using the microimmunofluoresence method.  Subjects were asked about their use of asthma medicines, symptoms, previous hospitalization for asthma, smoking status and age of onset of asthma.  In subjects with IgG titres of > or =1:64 and/or IgA titres > or =1:16 (n=212), spirometry was performed and peak expiratory flow rate (PEFR) and symptoms were recorded twice daily for 4 weeks on a diary card.  The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids.  There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04).  In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04).  Higher titres of antibodies to Chlamydia pneumoniae appears to be associated with markers of asthma severity.  This raises the possibility that chronic infection with Chlamydia pneumoniae leads to an increase in the severity of asthma.  Studies aimed at eradicating chronic infection with Chlamydia pneumoniae are necessary to determine whether or not this is the case.

Dept of Medicine
University of Auckland
New Zealand.

[Acute respiratory Chlamydia pneumoniae infections in adults. Value of direct gene amplification diagnosis] Infections respiratoires aigues de l'adulte a Chlamydia pneumoniae. Interet du diagnostic direct par amplification genique.

Chlamydia pneumoniae
Chlamydia Infections
Polymerase Chain Reaction
Respiratory Tract Infections
Acute Disease
Adult
Aged
Aged, 80 and over
Antibodies, Bacterial
Asthma
Community-Acquired Infections
Comparative Study

DNA, Bacterial
English Abstract
Enzyme-Linked Immunosorbent Assay
Female
Human
Lung Diseases
Lung Diseases, Obstructive
Male
Middle Age
Medline Database
Healthstar Database

Abstract
Chlamydia pneumoniae has been established recently as an important human respiratory pathogen.  The aim of this study was to define the incidence of Chlamydia pneumoniae in acute respiratory infections by evaluating its presence in posterior nasopharyngeal aspirates or broncho-alveolar lavage specimens by polymerase chain reaction- hybridization (PCR-EIA) as well as the titres of specific antibodies in serum by a rELISA test and a micro-immunofluorescence (MIF) test. 68 adults patients were investigated.  Eight patients (11.8%) were positive by either rELISA or PCR-EIA or both, with an infection rate of 5 patients with community-acquired pneumonia, 2 asthmatic patients and 1 patients with an exacerbation of chronic obstructive pulmonary disease.  Serological evidence of acute infection was found in four of these patients with rELISA test and in three others with MIF test.  PCR-EIA detected Chlamydia pneumoniae DNA in four patients, but there were concordant results with rELISA and PCR-EIA in only one patient.  In conclusion, Chlamydia pneumoniae appears to be a common etiologic agent of acute respiratory infections in adults.  The discrepancy between serological test and PCR-EIA results reflects the difficulties in routine laboratory diagnosis of Chlamydia pneumoniae.  The ambiguous results of serological tests from a single serum sample assess the utility of PCR for prompt diagnosis.  When PCR is negative or no feasible, a second serology to 15/21 days of interval is necessary.  Further studies with optimised techniques must be developed.

Service de Pneumologie
Hopital Cote de Nacre
CHRU de Caen. bellini@club-internet.fr

Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children.

Freymuth F,      Vabret A,      Brouard J,      Toutain F,      Verdon R,      Petitjean J,      Gouarin S      Duhamel JF,      Guillois B     

Asthma
Chlamydia Infections
Pneumonia, Mycoplasma
Respiratory Tract Infections
Virus Diseases
Viruses
Adolescence
Child
Child, Preschool

Chlamydia pneumoniae
Fluorescent Antibody Technique
Human
Infant
Mycoplasma pneumoniae
Picornaviridae Infections
Polymerase Chain Reaction
Support, Non-U.S. Gov't

Abstract
BACKGROUND: A high frequency of virus infections has been recently pointed out in the exacerbations of asthma in children. 

OBJECTIVES: To confirm this, using conventional and molecular detection methods, and expanding the study to younger children. 

STUDY DESIGN: One hundred and thirty-two nasal aspirates from 75 children hospitalized for a severe attack of asthma were studied (32 infants, mean age 9.1 months; and 43 children, mean age 5.6 years).  According to the virus, a viral isolation technique, immunofluorescence assays (IFA) or both were used for the detection of rhinovirus, enterovirus, respiratory syncytial (RS) virus, adenovirus, coronavirus 229E, influenza and parainfluenza virus.  Polymerase chain reaction (PCR) assays were used for the detection of rhinovirus, enterovirus, RS virus, adenovirus, coronavirus 229E and OC43, Chlamydia pneumoniae and Mycoplasma pneumoniae. 

RESULTS: Using IFA and viral isolation techniques, viruses were detected in 33.3% of cases, and by PCR techniques, nucleic acid sequences of virus, Chlamydia pneumoniae and Mycoplasma pneumoniae were obtained in 71.9% of cases.  The combination of conventional and molecular techniques detects 81.8% of positive samples.  Two organisms were identified in the same nasal sample in 20.4% of the cases.  The percentage of detections was higher (85.9%) in the younger group than in the other (77%).  The most frequently detected agents were rhinovirus (46.9%) and RS virus (21.2%).  Using PCR rather than conventional techniques, the detection rates were increased 5.8- and 1.6-fold in rhinovirus and RS virus infections, respectively.  The detection levels of the other organisms are as follows: 9.8, 5.1, 4.5, 4.5, 4.5, 3.7, and 2.2% for enterovirus, influenza virus, Chlamydia pneumoniae, adenovirus, coronavirus, parainfluenza virus, and Mycoplasma pneumoniae, respectively. 

CONCLUSION: These results confirm the previously reported high frequency of rhinovirus detection in asthmatic exacerbations in children.  They also point out the frequency of RS virus detection, and emphasize the fact that PCR assays may be necessary to diagnose respiratory infections in asthma.

Laboratory of Human and Molecular Virology
University Hospital
Caen
France. freymuth-f@chu-caen.fr

Asthma, atopy and Chlamydia pneumoniae antibodies in adults.

Von Hertzen L,      Toyryla M,      Gimishanov A,      Bloigu A,      Leinonen M,      Saikku P      Haahtela T     

Adult
Female
Human
IgG
Male

Middle Age
Sex Factors
Support, Non-U.S. Gov't
Medline Database
Healthstar Database

Abstract
BACKGROUND: Factors involved in the development of inflammation and asthma in nonatopic subjects have remained largely obscure, although there is some evidence to suggest that certain infections may play a role. 

OBJECTIVE: We investigated the association between serological evidence of Chlamydia pneumoniae infection and asthma in adults, and the possible modifying effect of the patients' atopic status on this association. 

METHODS: Four hundred and thirty consecutive patients who attended the hospital between 1992 and 1993 with symptoms suggestive of asthma, rhinitis or allergy were enrolled.  Diagnostic procedures including lung function measurements and skin-prick tests were performed in all patients.  The patients with established asthma (n = 332) were divided into those with recent asthma (n = 224, onset 1985 onward) and longstanding asthma (n = 108, onset before 1985).  The controls (n = 98) comprised all subjects who did not meet the criteria of asthma.  Serum immunoglobulin (Ig)G, IgA and IgM antibodies to C. pneumoniae were measured by the microimmunofluorescence test. 

RESULTS: In women, the prevalences of elevated IgG (a titre of >/= 128) and IgA (>/= 32) antibody levels and the age-adjusted geometric mean titres (GMT) of IgG and IgA antibodies were invariably highest among subjects with nonatopic longstanding asthma.  Elevated IgG titres in women occurred in 11% of controls, in 28% of nonatopic recent onset asthmatics, and in 43% of asthmatics with nonatopic longstanding disease; for men the respective figures were 33, 50 and 64%.  Logistic regression analysis controlling for age, sex and smoking showed that asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae (odds ratio 3.3, 1.6-6.8 for longstanding asthma, 2.3, 1. 2-4.4 for recent asthma, and among women only 4.2, 1.6-10.9 for longstanding asthma, and 3.0, 1.3-7.2 for recent asthma).  When the atopics and nonatopics were analysed separately, an even stronger relationship in the nonatopics was obtained for longstanding asthma (6.0,2.1-17.1).  In contrast, the relationship between atopic asthma, either recent or longstanding, and elevated IgG titres was not significant, indicating that asthma per se does not predispose to C. pneumoniae infection. 

CONCLUSIONS: Asthma was significantly associated with elevated IgG antibody levels to C. pneumoniae, and this association was strongest for nonatopic longstanding asthma.

Finnish Lung Health Association
Helsinki
Finland.

The role of viral and atypical bacterial pathogens in asthma pathogenesis.

Johnston SL     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Picornaviridae Infections

Rhinovirus
Child
Human
Infant

Review
Review Literature

Abstract
The recent development of PCR for the diagnosis of respiratory viral infections has permitted studies revealing the importance of virus infections in acute exacerbations of asthma.  Several studies implicate rhinovirus as the major virus type in mild and severe wheezing illness in children of all age groups, but particularly over 1 year of age.  Rhinoviruses have been shown to replicate in the lower airway, suggesting that virus induced asthma exacerbations result from direct inoculation, spread of the virus from the upper to the lower airway.  The importance of RS virus infection in bronchiolitis and wheezing in infants has been reaffirmed.  Recent studies using PCR to detect C pneumoniae, suggests a high prevalence of chronic infection in asthmatic children, and that the immune response to this organism may play a pathological role in asthma.  These studies now require confirmation with larger carefully controlled studies.

Southampton General Hospital
UK.

Chlamydia pneumoniae and possible relationship to asthma. Serum immunoglobulins and histamine release in patients and controls.

Larsen FO,      Norn S,      Mordhorst CH,      Skov PS,      Milman N,      Clementsen P     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Histamine Release
Immunoglobulins
Adolescence
Adult

Antibodies, Bacterial
Female
Human
Male
Middle Age
Support, Non-U.S. Gov't

Abstract
Chlamydia pneumoniae (C.pn.) is claimed to be of importance for the development of bronchial asthma in previously healthy individuals.  This is a new and speculative theory.  Earlier studies have mainly focused on C.pn. and exacerbation of asthma.  If this new theory were true, one would expect titres of C.pn.-specific IgG to be higher or more common in patients compared with controls.  It would also seem probable that pathobiological mechanisms as found in connection with other microorganisms could be demonstrated, i.e. presence of C.pn.- specific IgE and the capability of C.pn. to induce or enhance histamine release from basophil leukocytes.  We therefore examined C.pn.-specific IgE, IgG and IgM in sera from 22 adults with bronchial asthma and 25 healthy controls.  IgE was verified by passive sensitization of basophils from umbilical cord blood.  The prevalence of IgE was approx. 69% and IgG approx. 23% in both groups.  IgG-titres were between 1:16 and 1:64 in both groups.  No IgM was found.  Further, C.pn. could neither induce nor enhance histamine release from basophil leukocytes of patients or controls.  We conclude that patients with bronchial asthma and healthy controls do not differ in relation to 1) C.pn.-specific IgE in sera, 2) the capability of C.pn. to induce or enhance histamine release from basophil leukocytes, since no such effect was found, or 3) previous C.pn. infection judged by the presence of specific IgG antibodies.  Our results cannot support the theory that C.pn. is a cause of adult-onset asthma.

Department of Pharmacology
University of Copenhagen
Panum Institute
Denmark.

[Chlamydia pneumoniae infection in children with asthma exacerbation]

Kamesaki S,      Suehiro Y,      Shinomiya K,      Matsushima H,      Ouchi K     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Adolescence

Antibodies, Bacterial
Child
Child, Preschool
English Abstract

Female
Human
Infant
Male

Published in Japanese

Abstract
Little is known about the significance of C. pneumoniae in wheezing state in children.  In this study, a total of 33 children with exacerbation of bronchial asthma were serologically and bacteriologically analyzed to investigate whether C. pneumoniae infection is associated with wheezing in children with bronchial asthma. 1) Of the 33 patients 12 (39%) had an acute antibody rise against C. pneumoniae.  C. pneumoniae was isolated from 8 patients (24%) by culture.  Based on these findings, 15 cases (45%) were diagnosed as C. pneumoniae infection. 2) There were no significant difference in clinical signs, symptoms and laboratory studies between with and without C. pneumoniae infection.  The high incidence of C. pneumoniae infection in children with exacerbation of bronchial asthma suggests its significance as a cause of wheezing.  Although there was no specific symptom in C. pneumoniae infection, this infection should be suspected in wheezing children for diagnosis and proper treatment.

Center of Allergy and Clinical Immunology
Saiseikei Nakatsu Hospital.

Chlamydia pneumoniae and asthma [see comments]

Cook PJ,      Davies P,      Tunnicliffe W,      Ayres JG,      Honeybourne D,      Wise R     

Asthma
Chlamydia Infections
Chlamydia pneumoniae
Acute Disease
Adolescence
Adult
Aged
Aged, 80 and over
Antibodies, Bacterial
Chronic Disease

Female
Hospitalization
Human
IgG
Male
Middle Age
Prospective Studies
Support, Non-U.S. Gov't
Medline Database
Healthstar Database

Abstract

BACKGROUND: This study was designed to test the association of Chlamydia pneumoniae infection with asthma in a multi-racial population, after adjustments for several potential confounding variables. 

METHODS: Antibodies to C pneumoniae were measured by microimmunofluorescence in 123 patients with acute asthma, 1518 control subjects admitted to the same hospital with various non- cardiovascular, non-pulmonary disorders, and 46 patients with severe chronic asthma, including some with "brittle" asthma.  Acute infection or reinfection was defined by titres of IgG of > or = 512 or IgM > or = 8 or a fourfold rise in IgG, and previous infection by IgG 64-256 or IgA > or = 8.  Logistic regression was used to control for likely confounders, including ethnic origin, age, sex, smoking habit, steroid medication, diabetes mellitus and social deprivation, on antibody levels. 

RESULTS: Antibody titres consistent with acute C pneumoniae infection were found in 5.7% of patients with acute asthma and 5.7% of control patients, while 14.6% of patients with acute asthma and 12.7% of control patients had titres suggesting previous infection.  These two groups did not differ significantly.  However, titres suggesting previous infection were found in 34.8% of patients with severe chronic asthma: the difference between this group and the control group was statistically significant with an adjusted odds ratio of 3.99 (95% confidence interval 1.60 to 9.97). 

CONCLUSIONS: These data raise important questions about the previously demonstrated association of C pneumoniae infection with asthma, and suggest that future studies of this association should give particular attention to the presence or absence of a history of severe chronic asthma.

Comment in: Thorax 1998 Dec;53(12):1095

Department of Respiratory Medicine
City Hospital
Birmingham
UK.

Construction of an internal control for the detection of Chlamydia pneumoniae by PCR.

Ursi D,      Ieven M,      Van Bever HP,      Goossens H     

Chlamydia pneumoniae
Polymerase Chain Reaction
Asthma
Bronchiolitis
Child
Child, Preschool

Chlamydia Infections
DNA Primers
DNA, Bacterial
Human
Reference Standards
Retrospective Studies

Abstract
For the detection of Chlamydia pneumoniae by polymerase chain reaction (PCR) in respiratory samples, an internal control was constructed to monitor the efficiency of amplification in each reaction.  The internal control was designed in a way that the same primer pair can be used to amplify the internal control and target DNA.  Nasopharyngeal aspirates of children suffering from asthma(> 2 years of age; 24 patients) or bronchiolitis (< 2 years of age; 47 patients) were analysed for the presence of C. pneumoniae, using the internal control in each amplification reaction.  Two specimens from asthma patients, both children of 8 years old, were positive for C. pneumoniae.  The number of cases studied is too small to draw conclusions regarding the incidence of C. pneumoniae in different age categories in children.

Department of Microbiology
University Hospital Antwerp
Edegem
Belgium.

Clinical aspects of chlamydia respiratory tract infections and their role in the pathogenesis of asthma Kliniczne aspekty chlamydiowych zaka~zen ukladu oddechowego i ich rola w patogenezie astmy.

Szulakowski P,      Pierzchala W     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Adult
Animal
Bronchoalveolar Lavage Fluid

Child
English Abstract
Human
Serologic Tests
Review
Review, Tutorial

Published in Polish

Abstract
Recent world-wide publications were reviewed in order to determine the clinical characteristics and therapeutic relevance of the chlamydial respiratory tract infections in humans.  It was emphasized that Chlamydia pneumoniae could initiate asthma and may be associated with acute asthma exacerbation.  Laboratory procedures for identifying chlamydia and difficulties concerned with the diagnostics of this intracellular pathogen were also presented.  In patients with evidence of chlamydial infection the casual treatment (macrolides, tetracyclines, fluoroquinolones) may induce major improvement or complete resolution of asthma.

Katedry i Kliniki Pneumonologii Slaskiej Akademii Medycznej
Katowicach.

Chronic Chlamydia pneumoniae infection and asthma exacerbations in children.

Cunningham AF,      Johnston SL,      Julious SA,      Lampe FC,      Ward ME     

Asthma
Chlamydia pneumoniae
Chlamydia Infections
Antibodies, Fungal
Child
Chronic Disease

DNA, Fungal
Human
Mycoplasma pneumoniae
Nasal Mucosa
Polymerase Chain Reaction
Support, Non-U.S. Gov't

Abstract
 This study was undertaken to investigate the reported association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and the expression of asthma-related symptoms.  One hundred and eight children with asthma symptoms, aged 9-11 yrs, completed a 13 month longitudinal study.  The children maintained a daily diary of respiratory symptoms and peak flow rates.  When respiratory symptoms were reported an investigator was called and a nasal aspirate obtained.  In total 292 episodes were reported.  After the study 65 children provided samples when asymptomatic.  The presence of infection was investigated by the polymerase chain reaction for C. pneumoniae and M. pneumoniae and C. pneumoniae secretory immunoglobulin A (IgA) was detected by amplified enzyme immunoassay.  C. pneumoniae detections were similar between the symptomatic and asymptomatic episodes (23 versus 28%, respectively).  Children who reported multiple episodes also tended to remain PCR positive for C. pneumoniae suggesting chronic infection (p< 0.02).  C. pneumoniae- specific secretory-IgA antibodies were more than seven times greater in subjects who reported four or more exacerbations in the study compared to those who reported just one (p<0.02).  M. pneumoniae was found in two of 292 reports and in two of 65 asymptomatic samples.  In conclusion, chronic Chlamydia pneumoniae infection is common in schoolage children and immune responses to C. pneumoniae are positively associated with frequency of asthma exacerbations.  We suggest that the immune response to chronic C. pneumoniae infection may interact with allergic inflammation to increase asthma symptoms.  In contrast Mycoplasma pneumoniae was not found to be important in this study.

Molecular Microbiology
Southampton University Medical School
Southampton General Hospital
UK.

[Asthma and Chlamydia pneumoniae. A future prospect for macrolides in general and roxithromycin in particular?] Asthme et Chlamydia pneumoniae. Une perspective d'avenir pour les macrolides en general et pour la roxithromycine en particulier?

Antibiotics, Macrolide
Asthma
Chlamydia pneumoniae

Roxithromycin
Forecasting
Human

Review
Review, Tutorial

Published in French

Abstract
A LOGICAL HYPOTHESIS: Recent publications raise the question of an association between Chlamydia pneumoniae and asthma.  There has been no formal proof justifying routine search for C.pneumoniae in patients with uncontrolled asthma nor for systematic treatment with an antibiotic. 

OPEN QUESTIONS: Can Chlamydia pneumoniae infection initiate or aggravate asthma? Are acute manifestations of asthma associated with an overly high frequency of recent C.pneumoniae infection? Is a past history of C.pneumoniae infection abnormally frequent in patients with chronic asthma? PERSPECTIVES: Rigorously controlled clinical trials evaluating the efficacy of antibiotics such as macrolides which are active against C.pneumoniae are warranted to further elucidate these questions.

Centre de Pneumologie et de Reanimation respiratoire
Hopital Tenon
Paris.

Chlamydiae as pathogens: new species and new issues.

Peeling RW,      Brunham RC     

Chlamydia pneumoniae
Chlamydia psittaci
Chlamydia trachomatis
Chlamydia Infections
Ornithosis
Antibiotics, Macrolide
Antibiotics, Tetracycline
Asthma
Atherosclerosis
Azithromycin

Bacterial Outer Membrane Proteins
Clarithromycin
Host-Parasite Relations
Human
Polymorphism (Genetics)
Tetracycline
Review
Review, Tutorial
Medline Database
Healthstar Database

Abstract
The recognition of genital chlamydial infection as an important public health problem was made first by the recognition of its role in acute clinical syndromes, as well as in serious reproductive and ocular complications, and secondly by our awareness of its prevalence when diagnostic tests became widely accessible.  The recent availability of effective single dose oral antimicrobial therapy and sensitive molecular amplification tests that allow the use of noninvasive specimens for diagnosis and screening is expected to have a major impact in reducing the prevalence of disease in the next decade.  Clinical manifestations associated with Chlamydia pneumoniae infection continue to emerge beyond respiratory illness.  In particular, its association with atherosclerosis deserves further investigation.  Chlamydia pecorum, a pathogen of ruminants, was recently recognized as a new species.  The continued application of molecular techniques will likely elucidate an expanding role for chlamydiae in human and animal diseases, delineate the phylogenetic relationships among chlamydial species and within the eubacteria domain, and provide tools for detection and control of chlamydial infections.

Laboratory Centre for Disease Control Health
Winnipeg
Manitoba
Canada. rosanna_peeling@isdtcp3.hwc.ca

Serology of chlamydia in relation to asthma and bronchial hyperresponsiveness.

Bjornsson E,      Hjelm E,      Janson C,      Fridell E,      Boman G     

Abstract
Antibodies to the 3 strains of chlamydia were measured in the sera of 197 subjects; 122 with asthma-related symptoms and 75 from the general population.  The subjects underwent a structured interview, spirometry, a methacholine provocation test and skin-prick tests.  For chlamydia antibodies, IgG titer values of > or = 1:512 and/or IgM > or = 1:16 were regarded as evidence of a current or recent infection while IgG levels < 1:512 and > 1:32 were regarded as indicative of a previous infection.  For Chlamydia pneumoniae, a relationship was found between current or recent infection and wheezing odds ratio (OR) 6.0, confidence intervals (CI) 1.3-28) and also between IgA antibodies and bronchial hyperresponsiveness (BHR) (OR 3.3, CI 1.3- 8.3).  For Chlamydia trachomatis, serological signs of a previous infection were found significantly more often in subjects who reported having had asthma at some time: (OR 3.2, CI 1.4-7.1), asthma during the last year (OR 3.2, CI 1.4-7.1), wheezing during the last year (OR 4.2, CI 1.6-6.6) and in those who had BHR (OR 2.7, CI 1.2- 6.1).  We conclude that a relationship may exist between Chlamydia pneumoniae