Bacteria belonging to genus Chlamydia have a. Comparison of Individuals With and Without Specific IgA Antibodies to Chlamydia pneumoniae*

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1 Comparison of Individuals With and Without Specific IgA Antibodies to Chlamydia pneumoniae* Respiratory Morbidity and the Metabolic Syndrome Göran Falck, MD, PhD; Judy Gnarpe, PhD; Lars-Olof Hansson, MD, PhD; Kurt Svärdsudd, MD, PhD; and Håkan Gnarpe, MD, PhD Study objectives: To determine whether a correlation exists between markers for persistent Chlamydia pneumoniae infection, respiratory morbidity, and the metabolic syndrome. Design: Case-control study. A group of individuals with serologic markers (specific IgA > 1/128) suggestive of persistent C pneumoniae infection were compared with a group of control subjects without IgA antibodies (< 1/32). Setting: Apoteksgårdens Health Care Center, Kopparberg, Sweden. Participants: One hundred case subjects (61 men and 39 women) and 100 control subjects matched for age and gender (mean age, 55 years). Measurements and results: Individuals completed a questionnaire on respiratory symptoms and smoking habits. Body mass index (BMI) was calculated, BP, and peak expiratory flow (PEF) were determined. Blood specimens were drawn for determination of high-sensitivity C-reactive protein (hscrp), blood glucose level, serum lipids, and Chlamydia antibodies. No significant difference was found between case subjects and control subjects regarding myocardial infarctions, stroke, diabetes type II, BP, BMI, hscrp, blood glucose levels, and serum lipids. Symptoms of both asthma and chronic bronchitis were more common in case subjects, as were symptoms of chronic upper respiratory tract infections (p < 0.005). Case subjects with asthma or chronic bronchitis had more chronic upper respiratory tract disorders (p < 0.05). Symptoms of chronic respiratory tract diseases increased parallel to increasing specific C pneumoniae IgA antibody titers (p < ). PEF percentage of the predictive value was inversely correlated (p < ) to IgA antibody titers. Conclusion: The data show that persistent increased levels of C pneumoniae IgA antibodies were associated with pronounced respiratory dysfunction. These data provide additional evidence suggesting that IgA antibodies may be a marker for persistent C pneumoniae infection. (CHEST 2002; 122: ) Key words: asthma; cardiovascular diseases; Chlamydia pneumoniae; COPD; diabetes mellitus; IgA; lipids; persistent infection Abbreviations: AMI acute myocardial infarction; BMI body mass index; CVD cardiovascular disease; HDL highdensity lipoprotein; hscrp high-sensitivity C-reactive protein; PCR polymerase chain reaction; PEF peak expiratory flow; SOM secretory otitis media *From the Department of Public Health and Caring Sciences (Drs. Falck and Svärdsudd), Family Medicine Section, Uppsala University, Uppsala, Sweden; the Department of Medical Microbiology and Immunology (Dr. J. Gnarpe), University of Alberta, Edmonton, Canada; the Department of Clinical Chemistry (Dr. Hansson), Karolinska Laboratory, Karolinska Hospital, Stockholm, Sweden; and the Clinical Microbiology Section (Dr. H. Gnarpe), Institute of Bacteria belonging to genus Chlamydia have a tendency to cause chronic infections resulting in fibrosis and scarring. 1 Chlamydia pneumoniae may cause acute as well as chronic respiratory infections. 2 The bacterium has been associated with chronic rhinitis, 3 secretory otitis media (SOM), 4 chronic pharyngitis, 5 asthma, 6 and COPD. 7 In addition to these respiratory conditions, several seroepidemiologic investigations have shown C pneumoniae to be associated with cardiovascular disease (CVD), 8,9 hypertension, 10 stroke, 11,12 and atherogenic lipid pro- For editorial comment see page 1510 file. 13,14 An influence on the metabolic syndrome (elevated body mass index [BMI], blood glucose, Medical Sciences, University Hospital, Uppsala, Sweden. Funding received from the Swedish Society of Medicine. Manuscript received September 5, 2001; revision accepted April 16, Correspondence to: Göran Falck, MD, PhD, Apoteksgårdens Health Care Center, S Kopparberg, Sweden; g-falck@algonet.se CHEST / 122 / 5/ NOVEMBER,

2 systolic BP, and lowered high-density lipoprotein [HDL] cholesterol) has been reported. 15 The diagnostic criteria for C pneumoniae infection rely on determinations of specific antibodies. There are no generally accepted criteria for diagnosis of chronic C pneumoniae infection, but the presence of persistent levels of short-lived specific IgA antibodies to C pneumoniae has been associated with chronic C pneumoniae infection. 16 The objectives of this study were to determine whether specific C pneumoniae IgA antibodies were associated with respiratory morbidity, as suggested in previous studies, and with the metabolic syndrome. This was done by measuring peak expiratory flow (PEF), BMI, BP, high-sensitivity C-reactive protein (hscrp), blood glucose, serum lipids, and serum antibodies in a cohort of patients with increased C pneumoniae IgA antibody levels compared with a matched control group without C pneumoniae IgA antibodies. Materials and Methods This was a case-control study. A group of individuals with titers of specific C pneumoniae IgA antibodies suggestive of persistent C pneumoniae infections was compared with a control group without IgA but matched for age, gender, and locality. Seven hundred ninety-six individuals 20 years of age were investigated at the same health-care center for markers of acute or chronic C pneumoniae infection from 1994 through One hundred thirty consecutive patients had sought medical advice for upper or lower respiratory tract infections. One hundred sixty-five specimens were obtained from healthy family members investigated during a disease transmission study. 17 The remaining 501 specimens were obtained from patients seeking medical advice for longstanding upper or lower respiratory tract infections. Inclusion Criteria Case Subjects: All patients who had specific C pneumoniae IgA antibody titers 1/128 in repeated specimens over a period of at least 6 months were included. Control Subjects: Patients with specific C pneumoniae IgA antibody titers 1/32 during the last 6 months before the study were considered potential control subjects. From this group, subjects were matched to the case subjects by gender and age as closely as possible to form a control group. Other potential confounding variables were to be adjusted in the statistical analysis. Questionnaire All case and control subjects completed a questionnaire based on the British Medical Research Council questionnaire on respiratory symptoms 18 with additional questions regarding chronic upper respiratory tract infections, hypertension, hyperlipidemia, angina pectoris, previous myocardial infarction, stroke, asthma, chronic bronchitis/emphysema, earlier antibiotic treatment, and smoking habits. All responses regarding recent disease(s) were checked and corrected against the individual s medical case records. Diabetes was defined as verified and treated hyperglycemia, hyperlipidemia was defined as verified and treated hyperlipidemia, and hypertension was defined as verified and treated hypertension. Acute myocardial infarction (AMI) was defined as either a hospitalization with a final diagnosis of AMI or as status postcoronary artery surgery; stroke was defined as hospitalization with a final diagnosis of stroke or transient ischemic attack. Asthma was defined as a positive response to four of five asthma-related questions in the questionnaire and need for asthma treatment in the last year. Chronic bronchitis/emphysema was defined as positive responses to four of five chronic bronchitis/emphysema-related questions in the questionnaire. Chronic upper respiratory disorders were defined as positive responses to questions on symptoms and to the question on duration (Table 1). Individuals who had never smoked were classified as nonsmokers; those who currently smoked or had quit within the last 12 months were classified as current smokers. Individuals who had quit smoking 12 months before inclusion were classified as ex-smokers. Clinical Investigations BMI was calculated for all case and control subjects. BP was measured after resting for 10 min. PEF was measured in standing subjects using a Mini-Wright Peak Flow Meter (Clement Clarke International LTD; Essex, UK). The highest of three readings was recorded. The predicted PEF values were taken from Quanjer. 19 C pneumoniae antibodies were analyzed by microimmunofluorescence at an accredited clinical microbiology laboratory using previously standardized and optimized technique and reagents. 20,21 Sera were diluted 1:32 with phosphate-buffered Table 1 Questionnaire Asthma Do you have a family history of asthma? Have you ever had asthma? Have you ever had asthma symptoms (attacks of shortness of breath, with or without cough and wheeze)? Do you have asthma diagnosed by a physician? Do you usually have wheezing or whistling sounds in your chest? History and symptoms of chronic bronchitis Have you ever had chronic bronchitis? Do you have chronic bronchitis or emphysema diagnosed by a physician? Have you had any long-standing period of cough in the last 5 years? If yes, have you had such periods lasting 3 months during 2 consecutive years? Do you have phlegm when coughing, or do you have phlegm in the chest that you cannot cough up? Chronic upper respiratory tract infections Have you the last year for 2 months had: Nasal congestion? Plugged ears? Mucus in the throat? Swollen throat or lump in the throat? Sore throat? Have you had longstanding symptoms ( 2 years) from: The nose? The ears? The throat? 1588 Clinical Investigations

3 saline solution, ph 7.4, and tested for IgG, IgA, and IgM antibodies using 21-well antigen slides with elementary bodies of Chlamydia psittaci, Chlamydia trachomatis, and C pneumoniae in each test well (LabSystems Oy; Helsinki, Finland). Sera found to be positive in screening dilutions for IgG were rediluted and tested in doubling dilutions. Sera positive for IgA or IgM were first absorbed with GullSorb (Gull Laboratories; Salt Lake City, UT) to remove IgG and then tested in doubling dilutions. Serum dilutions were incubated with antigen for 14 to 16 h at 4 C. Slides were washed thoroughly in three changes of phosphate-buffered saline solution, ph 7.4, then incubated with fluorescein isothiocyanate-conjugated rabbit antihuman IgG, IgA, or IgM (Dakopatts; Glostrup, Denmark) at 37 C for 30 min. Control sera with specified high and low titers were used on each testing occasion, and tests were accepted only if the titers were within one dilution step of the predetermined mean titers for the respective quality control sera. All tests were read with a Zeiss UV microscope (Zeiss; Jena, Germany) with a 40 oil immersion lens and a 10 ocular lens (total magnification, 400) by either of two experienced microbiologists. All titers reported in the Tables are expressed as reciprocals. Blood from all case and control subjects was analyzed at an accredited clinical chemistry laboratory for hscrp, blood glucose, and serum lipids (total cholesterol, HDL, low-density lipoprotein, and triglycerides). All specimens were obtained in the evening; the individuals were not fasting. This study was approved by the Ethics Committee in Örebro County Council, Sweden. Informed consent was obtained from all participants. Statistical Analysis Data were analyzed with the JMP program (SAS Institute; Cary, NC). Standard methods were used for computing means and SDs. Analysis of variance or the Student t test was used to compare means between groups. Ordinal data were analyzed with the 2 test. Trend tests across groups were performed with ordinal logistic regression, the results were checked with linear regression using IgA and IgG titers as dependent variables. Measure results were multivariate, taking the possible confounding influence of age, gender, and smoking habits into account (Table 2). All tests were two tailed. Probability values 0.05 were generally regarded as statistically significant. Very small p values were denoted even when they were much smaller. Results The characteristics and results for the case and control groups from the questionnaire are shown in Table 2; the clinical and laboratory investigations are shown in Table 3. PEF could not be measured in one control subject. Asthma and chronic bronchitis were more common among the case subjects. A significant difference was found between case and control subjects regarding the occurrence of chronic upper respiratory tract disorders (p 0.005; Table 2). Considerable overlapping was seen between individuals with asthma and symptoms of chronic bronchitis; 5 of 17 patients with asthma had symptoms of chronic bronchitis (4 case subjects and 1 control subject). Twelve of 19 case subjects and 2 of 11 control subjects with asthma or chronic bronchitis had chronic upper respiratory tract disorders (p 0.05). Smoking (smokers and ex-smokers) was common among case Table 2 Characteristics of Individuals With and Without Specific IgA Antibodies to C pneumoniae* Control Subjects Case Patients p Values Variables IgA 32, Group A IgA , Group B IgA 512, Group C Group A Group B Group A Group C Trend Characteristics Patients, No Male/female gender, No. 61/39 34/27 27/12 NS NS NS Mean (SD) age, yr 55.2 (12.9) 55.0 (13.2) 56.5 (13.5) NS NS NS Age range, yr NS NS NS Questionnaire Nonsmokers 51 (51) 30 (49) 11 (28) NS NS NS Ex-smokers 26 (26) 16 (26) 13 (33) NS NS NS Current smokers 23 (23) 15 (25) 15 (38) NS NS NS Antibiotic treatment last year 24 (24) 22 (36) 26 (66) Treated diabetes 4 (4) 7 (11) 3 (8) NS NS NS Treated hypertension 19 (19) 7 (11) 8 (21) NS NS NS Treated hyperlipidemia 2 (2) 4 (7) 1 (3) NS NS NS Evidence of coronary disease 8 (8) 6 (10) 4 (10) NS NS NS Evidence of stroke 2 (2) 2 (3) 0 (0) NS NS NS Individuals with disease 25 (25) 16 (26) 11 (28) NS NS NS Treated asthma 7 (7) 3 (5) 7 (18) NS NS Chronic bronchitis/emphysema 4 (4) 3 (5) 6 (15) NS Chronic upper respiratory tract 11 (11) 13 (21) 16 (41) disorders Chronic respiratory disorders 20 (20) 15 (25) 21 (54) *Data are presented as No. (%) unless otherwise indicated. Antibody titers are inverted. NS not significant. CHEST / 122 / 5/ NOVEMBER,

4 Table 3 Characteristics of Individuals With and Without Specific IgA Antibodies to C pneumoniae* Control Subjects Case Patients p Values Variables IgA 32, Group A IgA , Group B IgA 512, Group C Group A Group B Group A Group C Trend Patients, No Physical measurements BMI 26.6 (4.3) 27.1 (3.6) 26.8 (5.7) NS NS NS BP, mm Hg Systolic 140 (22.5) 139 (20.9) 142 (24.2) NS NS NS Diastolic 83 (11.0) 82 (8.9) 83 (15.1) NS NS NS PEF, % of predictive value 111 (16.5) 107 (20.1) 99 (26.0) Blood chemistry hscrp, mg/l 3.49 (5.4) 4.70 (9.1) 6.48 (9.9) NS NS NS Glucose, mmol/l 5.52 (1.5) 5.98 (2.8) 6.16 (2.6) NS NS NS Total cholesterol, mmol/l 6.13 (1.3) 6.10 (1.5) 5.83 (1.0) NS NS NS HDL, mmol/l 1.46 (0.3) 1.46 (0.3) 1.46 (0.4) NS NS NS LDL, mmol/l 1.16 (0.9) 1.05 (0.3) 1.02 (0.3) NS NS NS Triglyceride, mmol/l 2.44 (2.6) 2.92 (5.5) 2.26 (1.3) NS NS NS C pneumoniae mean inverted antibody levels IgG ,887 IgA ,011 *Data are presented as mean (SD) unless otherwise indicated. Antibody titers are inverted. LDL low-density lipoprotein. See Table 2 for expansion of abbreviation. subjects with symptoms of asthma (12 of 17 subjects) and chronic bronchitis (12 of 13 subjects). Thirteen of the fourteen cases with an IgA titer of 1/1,024 had persistent symptoms from the respiratory tract compared with only three of the control subjects. The case subject without symptoms according to the questionnaire had a verified COPD with an FEV 1 of 45% of the predicted value. Symptoms of chronic respiratory tract diseases in case and control subjects increased parallel to increasing C pneumoniae-specific IgA antibody titers (Table 4). Case subjects with asthma had 85% of predictive PEF values vs 99% for control subjects. The same was found for case and control subjects with chronic bronchitis (75% vs 103%, respectively). An inverse correlation was found between increasing IgA Table 4 C pneumoniae IgA Antibody Levels Related to Chronic Symptoms From the Respiratory Tract* IgA, Inverted Titers Chronic Symptoms From the Respiratory Tract No. % of Total 32 20/ / / / ,024 7/8 88 2,048 3/ ,096 3/3 100 *Test for trend, p (p ) and IgG (p 0.05) antibody titers and PEF values independent of smoking (Table 5). The two case subjects with the highest specific IgA titers (1/4,096) had cancer of the respiratory tract. One case subject had cancer in situ of the larynx that had been removed surgically with postoperative ir- Table 5 PEF Percentage of Predictive Value Correlated to Specific C pneumoniae Antibodies* Inverted Titers No. PEF, % of Predictive Value IgA* , , , IgG , , , , *Test for trend, p Test for trend, p Clinical Investigations

5 radiation therapy. This case subject was repeatedly positive for C pneumoniae by culture and by polymerase chain reaction (PCR) from throat specimens. PCR performed on part of the removed tumor was positive for C pneumoniae. The second case subject had a chronic SOM and COPD. This patient had lung cancer with metastatic bone growth. It was not possible to obtain tissue samples of the tumor for C pneumoniae diagnostics. No significant difference was found between groups regarding myocardial infarction, stroke, and diabetes type II, but 10 case subjects had diabetes compared with 4 control subjects (Table 2). BMI and BP were similar in both groups. hscrp was slightly increased in case subjects. No difference between groups was found regarding blood glucose levels or serum lipids (Table 3). Correction for treatment with statins during the last year in 5 case subjects and 2 control subjects, and for antibiotic treatment during the last year in 47 case subjects and 24 control subjects did not change the results. Discussion All 796 patients in the cohort from which the case and control subjects were selected had been examined at the same health-care center and came from the same geographic area. There was no special selection of patients at the health-care center. The population investigated should be representative for patients seeking medical advice at primary care centers. Smokers and ex-smokers were more common in the case group than in the control group. C pneumoniae infection is known to be more common in smokers, and smoking is supposed to predispose for the development of a chronic C pneumoniae infection. von Hertzen 25 suggested that the synergistic negative effect of smoking and C pneumoniae may be one mechanism in the pathogenesis of airway obstruction. C pneumoniae has been associated with several chronic conditions, eg, chronic rhinitis, 3 SOM, 4 chronic pharyngitis, 5 asthma, 6 COPD, 25 lung cancer, 26 and CVD, 8,9 including stroke. 11,12 Because CVD is a significant health problem globally, and COPD is a common cause of death, it is important to find a good marker for persistent C pneumoniae infection. 27 There are no universally accepted criteria for the diagnosis of chronic C pneumoniae infection. Microimmunofluorescence serology remains the gold standard for clinical diagnosis. Persistent, usually short-lived 28 specific IgA antibodies to C pneumoniae have been studied as markers of persistent infection, 16 and have been used as criterion for the definition of chronic C pneumoniae infection in several studies. 7,29 34 In prospective studies, our group 35 and Ekman et al 36 have shown that specific IgA antibody levels reflect the course of disease in adults better than IgG antibodies. We have shown that high specific IgA antibody titers may remain elevated for several years. 37 Our group has also reported a significant correlation between the amount of specific IgA antibodies and disease duration. 38 In a study on chronic pharyngitis, we had the opportunity to follow the development of IgA antibodies. 5 Two patients were followed up with repeated blood specimens for antibody analysis as well as biopsy specimens obtained from the retropharyngeal mucous membrane. These patients initially had no specific C pneumoniae IgA antibodies and were negative for C pneumoniae antigen by immunohistochemistry. When repeat blood specimens and pharyngeal biopsy specimens were obtained because of persistent symptoms after 7 months and 9 months, respectively, both patients were positive for C pneumoniae by immunohistochemistry, and had specific C pneumoniae IgA antibodies in titers of 1/256 and 1/512, respectively. Six years later, one of the patients still has chronic pharyngitis and C pneumoniae IgA titers of 1/1,024. The aim of this study was to compare individuals with probable chronic C pneumoniae infection to individuals without serologic markers for persistent C pneumoniae infection. To do this, we chose a specific C pneumoniae IgA antibody level of 1/128 as a cutoff titer. However, the results of our investigation suggest that a better antibody cutoff would be 1/512 to 1/1,024. Thirty-nine percent of cases with specific C pneumoniae IgA antibodies 1/512 and 100% of those with C pneumoniae IgA 1/1024 had chronic respiratory tract symptoms. Our data suggest that persistent increased levels of C pneumoniae IgA antibodies can be interpreted as a marker for persistent C pneumoniae infection. Leinonen and Saikku 15 reported a correlation between chronic C pneumoniae infection and the metabolic syndrome, and Laurila et al 13 and Murray et al 14 reported a serum lipid profile known to be a risk factor for atherosclerosis with increased levels of triglycerides, total cholesterol, and decreased HDL. However, we found no differences between case and control subjects regarding BMI, BP, blood glucose, and HDL. Our results corroborate those of Nishimura et al 39 and do not support a connection between C pneumoniae and the metabolic syndrome. We found no association between increased levels of C pneumoniae antibodies and adverse cardiovascular events (AMI or stroke) in this cohort of individuals with respiratory tract infections, but 10 of CHEST / 122 / 5/ NOVEMBER,

6 our case subjects and 4 control subjects had type II diabetes. To our knowledge, there are no other reports of an association between type II diabetes and increased C pneumoniae antibodies. Diabetes is a well-known risk factor for CVD. C pneumoniae infection has been found, in most studies, to be a risk factor for CVD, and it is possible that this may explain the higher incidence of diabetes in the group with increased C pneumoniae antibody titers. However, we cannot rule out an association because it was not possible in the scope of this study to examine all case subjects and control subjects by measurement of the carotid intima media thickness or by angiography. hscrp was increased in case subjects with IgA titers 1/512. This may be a reflection of a longer duration of chronic infection resulting in both higher antibody levels and C-reactive protein levels. Determination of hscrp levels was not valuable as a marker for the clinical diagnosis of persistent C pneumoniae respiratory infections. Hahn et al 6 reported an association between C pneumoniae and adult-onset asthma. This observation has been corroborated in several other studies; Cook et al 40 found that patients with severe asthma more often had increased levels of specific C pneumoniae IgG and IgA. These findings are in agreement with our observation that four of the individuals with asthma also fulfilled the criteria for chronic bronchitis. Hahn et al 34 have shown that persistent elevated C pneumoniae IgA antibodies, in contrast to specific IgG antibodies, are good markers for infection-induced adult asthma. In this study, patients with symptoms of asthma and C pneumoniae IgA antibodies in titers of 1/128 had reduced predictive PEF compared with the control subjects without specific IgA. The predictive PEF was inversely correlated to increasing levels of specific IgA C pneumoniae antibodies but not to specific IgG antibodies. Our findings are in accordance with those of Black et al, 41 who also showed an inverse correlation between specific C pneumoniae IgG and IgA antibodies and FEV 1 in patients with asthma. These findings suggest that C pneumoniae infection may be associated with the etiology of or at least the severity of adult-onset asthma. A similar association between C pneumoniae infection and COPD has been reported by von Hertzen et al, 7 who showed that the highest specific IgA titers were found in patients with severe COPD. Wu et al 42 also report the finding of C pneumoniae by immunohistochemistry in patients with COPD. Conversely, Strachan et al 43 reported a negative association between chronic C pneumoniae infection and airflow obstruction in a population of 1,773 men, 45 to 59 years of age; however, the authors state: Our results for prevalent and incident chronic nonspecific lung disease are based on use by middle aged men of medications that are relatively specific for asthma, chronic bronchitis, emphysema or COPD rather than clinical diagnoses. They are more consistent with an association of COPD with IgA antibodies than with IgG titer, although neither association is significant. On the other hand, we cannot exclude a threefold increase in risk of chronic respiratory disease among the small proportion of men with high IgA titers ( 1/16). Future studies of C. pneumoniae serology in patients with airflow obstruction should assess both IgG and IgA antibodies. Only 20% of the men in this report had detectable IgA antibodies, which is a low percentage compared with the patients in our study. Patients with COPD are also usually 45 to 59 years old. In our study, men with symptoms of chronic bronchitis had a mean age of 66 years. Our results are in agreement with those of von Hertzen et al 7 : COPD patients with the highest specific IgA titers had the lowest predictive PEF values. This suggests that a chronic C pneumoniae infection in the lower respiratory tract may be associated with the development of obstructive respiratory tract disease. However, this particular study was not designed to investigate this relationship. The patients in this study are now being examined with spirometry in an attempt to verify these findings. It is interesting that two of the case subjects but none of the control subjects had cancer of the respiratory tract. Both case subjects had very high specific C pneumoniae IgA antibody levels. One of the case subjects was PCR positive for C pneumoniae in a larynx biopsy. This is in accordance with earlier observations by Laurila et al, 26 Koyi et al, 44 and Jackson et al, 45 who all reported an association between increased specific C pneumoniae IgA antibody levels and lung cancer. In conclusion, this study has shown a very strong association between high specific C pneumoniae IgA antibody levels and both upper and lower chronic respiratory tract conditions, often combined with obstructive disease in the lower respiratory tract. We suggest that increased specific C pneumoniae IgA antibodies are the most relevant and clinically significant marker for persistent C pneumoniae infection. References 1 Schachter J. Pathogenesis of chlamydial infections. Pathol Immunopathol Res 1989; 8: Hammerschlag MR, Chirgwin K, Roblin PM, et al. Persistent infection with Chlamydia pneumoniae following acute respiratory illness. Clin Infect Dis 1992; 14: Falck G, Engstrand I, Gnarpe J, et al. Chlamydia pneumoniae in chronic rhinitis. Presented at: 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, September 28 to October 1, Clinical Investigations

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