Chlamydia pneumoniae infection and inflammation in adults with asthma

BACKGROUND: Chlamydia pneumoniae infection and immune response to the C. pneumoniae heat shock protein 60 (CpHsp60) have been suggested to be associated with asthma. OBJECTIVES: To study whether a slightly elevated C-reactive protein (CRP) level as a marker of low-grade systemic inflammation has a role in this association, we collected serum and sputum samples from 103 asthma patients with disease severity ranging from mild to moderate and from 30 healthy volunteers. METHODS: IgA and IgG antibodies to C. pneumoniae elementary bodies (CpEB) and CpHsp60 were measured by enzyme immunoassay. Serum CRP levels were measured with a rapid two-site ultra-sensitive assay based on time-resolved immunofluorometry. RESULTS: The asthma patients, especially those with moderate asthma, had higher serum IgA antibody levels to CpHsp60 than the healthy controls (test for trend, p = 0.05), whereas antibody levels to CpEB antigen did not differ between the study groups. CRP levels were higher in both asthma groups compared to the control group and moreover, the patients with moderate asthma had higher CRP levels than those with mild asthma (test for trend, p < 0.01). The subjects with a slightly elevated CRP level, defined as > or =1.8 mg/l, had higher CpEB IgA (p = 0.001), CpEB IgG (p = 0.008) and CpHsp60 IgA (p = 0.023) antibody levels in serum compared to the subjects with lower CRP levels. CONCLUSIONS: Slightly elevated CRP levels as a marker of low-grade systemic inflammation may be associated with C. pneumoniae infection in asthma patients.     

Acute pancreatitis and serological evidence of infection with Mycoplasma pneumoniae

Paired acute and convalescent serum samples from 27 consecutive patients with acute pancreatitis were examined for evidence of infection with several viral agents. Evidence of infection with Coxsackie viruses group B was found in three patients, and of infection with Mycoplasma pneumoniae in nine patients (33%). This latter finding confirms recent reports from Scandinavia linking pancreatitis and serological evidence of infection with Mycoplasma pneumoniae. The possibility that a true association exists between the two conditions is considered, together with alternative explanations, and further work is envisaged to elucidate these findings.     

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

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.     

The development of asthma in wheezing infants with Chlamydia pneumoniae infection.

Chlamydia pneumoniae infection might play a role in the pathology of asthma, but its role in infantile asthma remains obscure. The presence of Chlamydia pneumoniae was serologically determined in wheezing infants who were then re-examined 1-year later to determine whether or not asthma is associated with this type of infection. Wheezing infants progressed to asthma more frequently after infection with Chlamydia pneumoniae than those who were not infected. These findings suggested that Chlamydia pneumoniae infection triggers asthma in wheezy infants.     

Role of Chlamydia pneumoniae infection in asthma in Northeast of Iran

The role of Chlamydia pneumoniae in asthma has drawn much attention in recent years. In this study we assessed the prevalence of C. pneumoniae infections in patients with chronic stable and acute exacerbation of asthma and compared it with normal population. Twenty adult patients with chronic stable asthma and 21 patients with acute exacerbations of asthma and 41 matched control subjects were studied for presence of C. pneumoniae using cell culture. This study suggests that positive results of C. pneumoniae culture are associated with both chronic stable and acute exacerbation of asthma. It could be concluded that C. pneumoniae is a risk factor for either development or exacerbation of asthma.     

Chlamydia pneumoniae and severity of asthma

A substantial increase in the prevalence of asthma in the Western world during the last few decades has led to a continuous search for novel factors that might be involved in the development of the disease. We carried out a study to clarify whether there is a relationship between severity of asthma and Chlamydia pneumoniae-specific titres at the group level and whether antibodies to the 60 kDa chlamydial heat shock protein (chsp60) are associated with asthma. A total of 116 (31 men, 85 women) consecutive asthma patients from a chest clinic were recruited and divided into 3 groups according to the severity of the disease: there were 13 asthmatics with severe, 54 with moderate and 49 with mild asthma. In addition, 50 (31 men, 19 women) consecutive blood donors were enrolled to serve as a control group. Sera for the measurements of specific IgG, IgA and IgM antibodies using a microimmunofluorescence test and of chsp60 using an enzyme immunoassay were obtained upon enrolment and also 3-4 months later from the asthma patients. Severe and moderate asthma were found to be strongly associated with elevated IgA antibody levels to C. pneumoniae [odds ratio (OR) 5.58, 95% confidence interval (CI) 1.31-23.72 for severe and OR 5.65, 95% CI 2.05-15.53 for moderate asthma] in a logistic regression model. Furthermore, in women, the occurrence of elevated IgA antibody levels and the age-adjusted geometric mean titres of IgA antibodies were significantly higher among the asthmatics than the controls (p = 0.003 and 0.04, respectively). Antibodies to chsp60 occurred more frequently and in higher concentrations among the asthmatics than the controls, although the differences did not reach significance. In conclusion, severe and moderate asthma were significantly associated with elevated IgA antibody levels to C. pneumoniae suggestive of chronic infection. Antibodies to chsp60 did not prove to be a useful marker of such an infection among the asthmatics studied here.     

Chlamydia pneumoniae infection and Mycoplasma pneumoniae infection in pediatric patients

We evaluated a total of 1104 pediatric patients with acute lower respiratory tract infection for C. pneumoniae infection and M. pneumoniae infection by serology during July 1995 to December 1998. A microimmunofluorescence test was used for diagnosis of C. pneumoniae infection and a high density particle agglutination test for that of M. pneumoniae infection. Acute C. pneumoniae infection was found in 149 patients (13.5%), acute M. pneumoniae infection in 118 patients (10.7%), and dual infection in 27 patients (2.4%). Among 305 patients with pneumonia, M. pneumoniae infection (83 patients, 27.2%) was more common than C. pneumoniae infection (47 patients, 15.4%). However among 799 patients with bronchitis. C. pneumoniae infection (102 patients, 12.8%) was more common than M. pneumoniae infection (35 patients, 4.4%). Patients with C. pneumoniae infection were more younger and more frequently wheezing than patients with M. pneumoniae infection. These findings demonstrate that C. pneumoniae infection in very common pathogen of pediatric lower respiratory tract infection as M. pneumoniae infection in Japan.     

Chlamydia pneumoniae in otorhinolaryngological infection

I detail clinical observation, examination, and treatment of regional otorhinolaryngological infection 3-cases of acute sinusitis and 1 of acute pharyngitis-due to Chlamydia pneumoniae, occurring between January 2002 and December 2004. Special clinical features by infection with C. pneumoniae were not recognized in the 4 cases, while ordinary clinical features by conventional bacterial infection were recognized, such as pharyngalgia and pyrexia for acute pharyngitis and purulent discharge and headache for acute sinusitis. I diagnosed an infection for C. pneumoniae for 1 case with acute sinusitis by detecting a causative factor gene of C. pneumoniae by PCR. I diagnosed C. pneumoniae for the 2 other cases of acute sinusitis and the case of acute pharyngitis by confirming antibody titer of C. pneumoniae ascending by serological verification. The 1 adult acute sinusitis case and the acute pharyngitis case were treated using a new quinolone antimicrobial agent. I administered macrolides antimicrobial agent to the 2 acute pediatric sinusitis cases and attained good outcomes without recurrence. We wish to emphasize that C. pneumoniae infectionin in the otorhinolaryngological setting has not been adequately reported and has not received the attention it deserved. If a good outcome cannot be attained using the beta-lactam antimicrobial agent for otorhinolaryngological infection, it should be sought using a macrolides antimicrobial agent or the new quinolone antimicrobial agent for adults and with the macrolides antimicrobial agent for pediatric cases.     

肺炎衣原体感染与呼吸系统疾病的血清学相关性研究

目的　探讨肺炎衣原体 (Chlamydia Pneumoniae,CPn)感染与呼吸系统常见疾病的相关性。方法　采用间接免疫荧光法检测 CPn特异性抗体 Ig A、Ig G、Ig M。结果　肺癌组、慢性阻塞性肺疾病 (COPD)组和支气管哮喘组的既往感染率与慢性感染率明显高于自发性气胸组和健康献血员对照组 (P<0 .0 5 ) ;而肺癌组、COPD组和支气管哮喘组之间以及自发性气胸组和健康献血员对照组之间的感染率则无统计学意义 (P>0 .0 5 )。结论　 CPn血清特异性抗体 Ig A、Ig G的升高与肺癌、COPD和支气管哮喘相关 ,CPn感染可能参与了其发病机制。     

Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin

STUDY OBJECTIVES: To determine the effect of clarithromycin therapy in patients with asthma. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: A tertiary referral center. PATIENTS OR PARTICIPANTS: Fifty-five subjects with chronic, stable asthma recruited from the general Denver, CO, community. INTERVENTIONS: Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by treatment with clarithromycin, 500 bid, or placebo for 6 weeks. MEASUREMENTS AND RESULTS: Outcome variables were lung function, sinusitis as measured by CT, and the inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics. Treatment resulted in a significant improvement in the FEV(1), but only in the PCR-positive subjects (2.50 +/- 0.16 to 2.69 +/- 0.19 L, mean +/- SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 +/- 0.24 to 2.54 +/- 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects who received placebo. Sinus CTs revealed no change in sinusitis with clarithromycin treatment. In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects. However, the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-alpha (p = 0.006), IL-5 (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-alpha (p = 0.01) and IL-12 (p = 0.002) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.004). There were no significant differences in cytokine expression in those subjects who received placebo. CONCLUSIONS: These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae.     

Chlamydia pneumoniae infection and its role in asthma and chronic obstructive pulmonary disease.

Chlamydia pneumoniae (CP) is a common cause of respiratory tract infections, and several studies have asked whether it may play a pathogenic role in connection with bronchial asthma and chronic obstructive pulmonary disease (COPD). Evidence that CP infection is associated with these diseases is a cardinal item. However, evaluation of CP infection is hampered by difficulties in obtaining agreement on the definition of a gold standard. In the literature, serology is based on different cutoff points of antibody titres, which complicates the definition of CP seropositive findings and the classification of acute infection, chronic and past infection. In connection with acute and chronic infection, it is important to demonstrate the presence of CP by culture or polymerase chain reaction (PCR) in the respiratory tract, especially in the lower airways. Often, the results of serology is not associated with the findings by culture or PCR testing, which may involve the risk of inconclusive evidence. Evaluation of a possible presence of CP by clinical improvement after treatment with antibiotics is difficult since uncontrolled studies have been used and other microorganisms are also affected by antibiotics. Furthermore, many patients improve without antibiotics, and improvement has also been observed in patients remaining culture positive after treatment with antibiotics. It should also be noted that the antiinflammatory effects of antibiotics may improve the clinical status of patients. Despite these obstacles, studies point to the possibility that in some patients acute CP infections may lead to acute exacerbations of bronchial asthma. Whether a persistent CP infection contributes to chronic asthma or severe COPD, or whether it incites the diseases in previously healthy individuals is a question for further studies. Whether a causal relationship exists between CP infection and obstructive pulmonary disease or whether these patients are more susceptible to CP infection is unknown. Nevertheless, a cooperative role of CP in the proinflammatory mechanisms involved in these diseases remains to be examined since cellular studies show that CP stimulates the production and expression of cytokines, chemokines and adhesion molecules, actions that may amplify and prolong the inflammation.     

Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma

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.     

Chlamydia pneumoniae infection in asthmatic patients

This study was conducted on 30 asthmatic patients and 10 healthy controls. They were subjected to complete history talking, thorough clinical examination, and assessment of their ventilatory functions before and after bronchodilator. Two specimens were obtained from each patients, bronchoalveolar lavage and serum samples. Chlamydia pneumoniae antigens and antibodies (IgG and IgM) were detected using microimmunoflourescence technique. Samples giving positive results for C. pneumoniae antigen were examined for apoptosis. A significant correlation between asthma and C. pnumoniae was found especially in moderate and severe, long standing, steroid dependent asthma. In addition there was a significant difference between cases and controls regarding specific IgG and IgM. An association of C. pneumoniae with forced expiratory volume 1 (FEVI) was found. In addition C. pneumoniae was found to induce inhibition of programmed cell death. On conclusion, C. pneumoniae infection is associated with severe long standing asthma, and may be an important factor in acute exacerbation of asthma.     

Association of Chlamydia pneumoniae infection with diabetic nephropathy

We evaluated the association of Chlamydia pneumoniae (CP) infection with progression of diabetic nephropathy. Type 2 diabetic patients (60) were divided into two groups, those with incipient nephropathy and those with advanced nephropathy, based on the severity of diffuse glomerular lesions using Gellman's criteria. Type 2 (34) diabetic patients without nephropathy (normoalbuminuria) and 59 nondiabetics served as control groups. Serum IgG-antibody against CP was measured using ELISA. CP antibody was detected in 45.8% of nondiabetic controls, in 47.1% of diabetic patients without nephropathy, in 52.6% of diabetic patients with incipient nephropathy, and 78% of diabetic patients with advanced nephropathy. There was 4.22-fold increase in the risk of advanced nephropathy associated with the presence of CP antibody. Our findings indicate an association between chronic CP infection and advanced diabetic nephropathy.     

Placental infection with Chlamydia pneumoniae and intrauterine growth restriction

BACKGROUND: The concept that low birth weight infants are more predisposed to coronary artery disease (CAD) in adulthood has been studied extensively. Although many infectious agents have been associated with intrauterine growth restriction (IUGR), Chlamydia pneumoniae an organism implicated in CAD has not been investigated. It was our aim to assess whether C. pneumoniae DNA is present in placental tissue and whether its detection is associated with IUGR. METHODS: Fifty-nine pregnant women were studied: 32 women had an uncomplicated pregnancy with no antenatal or post-natal evidence of IUGR. Twenty-seven women had pregnancies with ultrasonographically demonstrated IUGR, defined as foetal abdominal circumference measuring less than 2 S.D.s from the mean for gestational age. At the time of delivery, maternal blood and placental tissue samples were obtained. Placental samples were taken from four sites centrally and peripherally on the maternal and foetal side of the placentas and tested by nested polymerase chain reaction for C. pneumoniae DNA. IgG antibodies to C. pneumoniae were measured using microimmunfluorescence. RESULTS: C. pneumoniae DNA was detected in 44% of the placental tissue but there was no difference in the prevalence of bacterial DNA between the control and the low birth weight group (P=0.58). Additionally C. pneumoniae seropositivity did not differ between the index and control groups (78 vs. 70%, P=0.44). CONCLUSIONS: C. pneumoniae is present in placental tissue. Its presence however does not correlate with IUGR. Similarly, maternal C. pneumoniae seropositivity is not related to low birth weight. Thus C. pneumoniae infection is unlikely to play a role in the pathogenesis of IUGR.     

Chlamydia pneumoniae infections in asthma: clinical implications

Chlamydia pneumoniae is an intracellular pathogen that has been suggested to play a role in the pathology of asthma. However, so far none of the studies have provided clear evidence for a causative role of C. pneumoniae infections in asthma, although there is little doubt that chronic C. pneumoniae infection does aggravate asthma and should be treated. The diagnosis of C. pneumoniae infection is still a matter of concern for it is dependent on trained skilled personnel and can vary significantly between different diagnostic laboratories. This fact is also one of the major problems encountered when comparing epidemiological studies investigating the possible role of C. pneumoniae infections and their impact on the pathogenesis of other diseases. With regard to therapy, long-term treatment with macrolides is the best available method to eradicate C. pneumoniae. Successful therapy for C. pneumoniae, however, can also be complicated by the high possibility of de novo infection as epidemiological studies have shown that the prevalence of antibodies to C. pneumoniae increases with age in all populations studied. In the northern hemisphere the prevalence of C. pneumoniae is also affected by seasonal conditions. It is too early to draw any conclusions from the equatorial belt countries. The available data on C. pneumoniae in tropical countries indicate a much faster infection rate during early adulthood with 100% serological prevalence at an age greater than 25 years. This data, if confirmed, would argue against C. pneumoniae causing asthma since the asthma prevalence in those countries does not increase in a parallel pattern. An alternative interpretation of most studies could be that the increased rate of C. pneumoniae infections in patients with asthma results from a modified susceptibility towards the microorganism, due to yet unknown changes of the host cell's physiology. It should be kept in mind that increased prevalence of C. pneumoniae infection is not restricted to asthma. Further studies are needed to understand the role of C. pneumoniae, especially of chronic infection, in the pathogenesis of inflammatory diseases with a specific focus on the effect that the microorganism triggers in the infected host cell. Only when we understand what C. pneumoniae does to its host cell will we be able to judge its impact on the overall status of an affected patient, and this knowledge will help us to develop a successful therapy.