Lisa A. Jackson

Standardizing Chlamydia pneumoniae Assays: Recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada)

Chlamydia pneumoniae has been associated with atherosclerosis and several other chronic diseases, but reports from different laboratories are highly variable and gold standards are lacking, which has led to calls for more standardized approaches to diagnostic testing. Using leading researchers in the field, we reviewed the available approaches to serological testing, culture, DNA amplification, and tissue diagnostics to make specific recommendations. With regard to serological testing, only use of microimmunofluorescence is recommended, standardized definitions for acute infection and past exposure are proposed, and the use of single immunoglobulin (Ig) G titers for determining acute infection and IgA for determining chronic infection are discouraged. Confirmation of a positive culture result requires propagation of the isolate or confirmation by use of polymerase chain reaction (PCR). Four of 18 PCR assays described in published reports met the proposed validation criteria. More consistent use of control antibodies and tissues and improvement in skill at identifying staining artifacts are necessary to avoid false-positive results of immunohistochemical staining. These standards should be applied in future investigations and periodically modified as indicated.

The burden of community-acquired pneumonia in seniors: results of a population-based study.

Abstract Background. Pneumonia is recognized as a leading cause of morbidity in seniors. However, the overall burden of this disease—and, in particular, the contribution of ambulatory cases to that burden—is not well defined. To estimate rates of community-acquired pneumonia and to identify risk factors for this disease, we conducted a large, population-based cohort study of persons aged ⩾65 years that included both hospitalizations and outpatient visits for pneumonia. Methods. The study population consisted of 46,237 seniors enrolled at Group Health Cooperative who were observed over a 3-year period. Pneumonia episodes presumptively identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned to medical encounters were validated by medical record review. Characteristics of participants were defined by administrative data sources. Results. The overall rate of community-acquired pneumonia ranged from 18.2 cases per 1000 person-years among persons aged 65–69 years to 52.3 cases per 1000 person-years among those aged ⩾85 years. In this population, 59.3% of all pneumonia episodes were treated on an outpatient basis. In multivariate analysis, risk factors for community-acquired pneumonia included age, male sex, chronic obstructive pulmonary disease, asthma, diabetes mellitus, congestive heart failure, and smoking. Conclusions. On the basis of these data, we estimate that roughly 915,900 cases of community-acquired pneumonia occur annually among seniors in the United States and that ∼1 of every 20 persons aged ⩾85 years will have a new episode of community-acquired pneumonia each year.

Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study

BACKGROUNDnPneumonia is a common complication of influenza infection in elderly individuals and could therefore potentially be prevented by influenza vaccination. In studies with data from administrative sources, vaccinated elderly people had a reduced risk of admission for pneumonia compared with unvaccinated seniors; however, these findings could have been biased by underlying differences in health between the groups. Furthermore, since most individuals with pneumonia are not treated in hospital, such studies should include both outpatient and inpatient events. We therefore assessed whether influenza vaccination is associated with a reduced risk of community-acquired pneumonia in immunocompetent elderly people after controlling for health status indicators.nnnMETHODSnWe did a population-based, nested case-control study in immunocompetent elderly people aged 65-94 years (cases and controls) enrolled in Group Health (a health maintenance organisation) during the 2000, 2001, and 2002 preinfluenza periods and influenza seasons. Cases were individuals with an episode of outpatient or inpatient community-acquired pneumonia (validated by review of medical records or chest radiograph reports). We randomly selected two age-matched and sex-matched controls for each case. The exposure of interest was influenza vaccination. We reviewed medical records to define potential confounders, including smoking history, presence and severity of lung and heart disease, and frailty indicators.nnnFINDINGSn1173 cases and 2346 controls were included in the study. After we adjusted for the presence and severity of comorbidities, as defined by chart review, influenza vaccination was not associated with a reduced risk of community-acquired pneumonia (odds ratio 0.92, 95% CI 0.77-1.10) during the influenza season.nnnINTERPRETATIONnThe effect of influenza vaccination on the risk of pneumonia in elderly people during influenza seasons might be less than previously estimated.nnnFUNDINGnGroup Health Center for Health Studies internal funds and Group Health Community Foundation fellowship grant.

Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults.

Pneumococcal conjugate vaccine use among young children has led to significant declines in invasive pneumococcal disease in the United States, but the impact on community-acquired pneumonia is unknown. We conducted population-based pneumonia surveillance among 794,282 Group Health members before and after infant vaccine introduction in 2000. We presumptively identified pneumonia episodes using diagnosis codes assigned to medical encounters and confirmed 17,513 outpatient and 6318 hospitalized events by reviewing chest radiograph reports or hospitalization records. There was evidence for a decline in rates of both outpatient and hospitalized pneumonia in children less than 1 year of age following vaccine introduction but there were no consistent reductions in pneumonia rates among older children and adults.

Prior lung disease and risk of lung cancer in a large prospective study

AbstractObjectives: While 75-90% of people who develop lung cancer are smokers, only a small proportion of smokers develop lung cancer. Identifying factors that increase a smokers risk of developing lung cancer may help scientists to better understand the etiology of lung cancer and more effectively target high-risk groups for screening.nMethods: Information on physician-diagnosed non-malignant lung diseases [asbestosis, asthma, chronic bronchitis or emphysema (CB/E), pneumonia, and tuberculosis] was obtained at baseline from 17,698 men and women involved in CARET, a randomized lung cancer prevention trial of beta-carotene and vitamin A among heavy smokers and asbestos-exposed workers. Hazard ratios for lung cancer were estimated through Cox regression models, after controlling for potential confounding factors, included smoking. Analyses were restricted to former and current smokers.nResults: During a median follow up of 9.1 years, 1028 cases of lung cancer occurred. Those who developed lung cancer were more likely to report a history of CB/E than controls (adjusted HR = 1.29, 95% CI: 1.09-1.53). In subgroup analyses, the association between a history of CB/E and lung cancer was stronger for those who were younger at diagnosis/reference, men in the heavy smoker cohort, former smokers, and those with squamous cell carcinomas. There was little association between a history of other lung diseases and lung cancer.nConclusions: Smokers with a history of CB/E may be at higher risk of developing lung cancer, independent of their smoking history.

New strategies are needed to improve the accuracy of influenza vaccine effectiveness estimates among seniors.

OBJECTIVEnThe magnitude of the benefit of influenza vaccine among elderly individuals has been recently debated. Existing vaccine effectiveness estimates derive primarily from observational studies, which may be biased. In this paper, we provide a methodological examination of the potential sources of bias in observational studies of influenza vaccine effectiveness in seniors and propose design and analysis strategies to reduce bias in future studies.nnnSTUDY DESIGN AND SETTINGnWe draw parallels to bias documented in observational studies of therapies in other areas of medical research including pharmacoepidemiology, discuss reasons why existing adjustment methods in influenza studies may not adequately control for the bias, and evaluate statistical approaches that may yield more accurate estimation of influenza vaccine effectiveness.nnnRESULTSnThere is strong evidence for the presence of bias in existing observational estimates of influenza vaccine effectiveness in the elderly and the failure of current adjustment methods to reduce bias.nnnCONCLUSIONnPromising approaches for reducing bias include obtaining more accurate information on confounders, such as functional status, avoiding all-cause death in favor of outcomes, such as pneumonia or influenza-related pneumonia, and evaluating the extent to which bias is reduced by these and other methods using the control period before influenza season.

Frequency of Serological Evidence of Bordetella Infections and Mixed Infections with other Respiratory Pathogens in University Students with Cough Illnesses

Banked acute-phase and convalescent-phase serum samples from a previous study of respiratory illness in university students were examined for significant (>/=2-fold) increases in ELISA titers of IgA and IgG antibody to Bordetella pertussis filamentous hemagglutinin, pertactin, and fimbriae-2 and >/=4-fold titer increases to agglutinogens by agglutination. ELISA titers of antibody to pertussis toxin could not be determined because of technical problems. Chlamydia pneumoniae infections were diagnosed by culture or by a >/=4-fold increase in immunofluorescence assay titer or a single high titer (>/=512). Mycoplasma pneumoniae, influenza A and B, adenovirus, and respiratory syncytial virus infections were diagnosed by >/=4-fold increases in complement fixation titer or a single high titer (>/=64). There were 319 subjects with cough of >/=5 days duration, and of these, 47 (15%) had significant increases in antibody to B. pertussis antigens; 26 (8%) had significant increases to fimbriae-2 or agglutinogens, indicative of B. pertussis infection, and 2 (1%) had evidence of non-B. pertussis bordetella infections. Seventeen (36%) had evidence of mixed infections or cross-reacting antibodies (influenza B infections, 5; adenovirus infections, 4; influenza A infections, 3; C. pneumoniae infections, 3; and M. pneumoniae infections, 2). Our findings suggest that bordetella infections are common in young adults with cough illnesses (incidence, 9%), and a surprising number of these are mixed infections with other respiratory pathogens.

Prolonged Afebrile Nonproductive Cough Illnesses in American Soldiers in Korea: A Serological Search for Causation

A serological study was undertaken to investigate infections in active-duty United States soldiers with illnesses characterized by prolonged, afebrile, nonproductive coughs. Fifty-four soldiers were enrolled with such illness of >/=2 weeks duration (case patients) along with 55 well soldiers (control subjects). Serum samples were tested for IgG and IgA antibody to 3 Bordetella pertussis antigens, pertussis agglutinins, IgM antibodies to Mycoplasma pneumoniae, IgM and IgG antibodies to Chlamydia pneumoniae, and IgM antibody to adenoviruses. Forty-six case patients (85%) had evidence of recent infection with Bordetella species, M. pneumoniae, or C. pneumoniae, and many had evidence of mixed infections; there were 27 Bordetella species, 20 C. pneumoniae, and 33 M. pneumoniae recent infections. Fifteen case patients had high titers of IgG or IgA to B. pertussis filamentous hemagglutinin without high titers of antibodies to other B. pertussis antigens, which suggested the presence of cross-reacting antibodies to M. pneumoniae and perhaps C. pneumoniae or unidentified infectious agent or agents. Since illnesses due to Bordetella species, M. pneumoniae, and C. pneumoniae can all be treated with macrolide antibiotics and B. pertussis illness can be prevented by immunization, and since military readiness was affected in 63% of the cases, it seems important to conduct further studies in military populations.

Statin use and risk of community acquired pneumonia in older people: population based case-control study

Objective To test the hypothesis that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of community acquired pneumonia. Design Population based case-control study. Setting Group Health, a large integrated healthcare delivery system. Population Immunocompetent, community dwelling Group Health members aged 65 to 94; two matched controls for each case with pneumonia. Information on comorbid illnesses and functional and cognitive status, potential confounders of the association between statin use and risk of pneumonia, came from medical record review and computerised pharmacy data. Main outcome measure Adjusted estimates of risk of pneumonia in relation to current statin use. Results 1125 validated cases of pneumonia and 2235 matched controls were identified. Compared with controls, cases were more likely to have chronic lung and heart disease, especially severe disease, and functional or cognitive impairment. Current statin use was present in 16.1% (181/1125) of cases and 14.6% (327/2235) of controls (adjusted odds ratio 1.26, 95% confidence interval 1.01 to 1.56). Among cases admitted to hospital and matched controls, current statin use was present in 17.2% (68/395) of cases and 14.2% (112/788) of controls (adjusted odds ratio 1.61, 1.08 to 2.39, compared with non-use). In people in whom statins were indicated for secondary prevention, the adjusted odds ratio for risk of pneumonia in relation to current statin use was 1.25 (0.94 to 1.67); in those with no such indication, it was 0.81 (0.46 to 1.42). Conclusions Statin use was not associated with decreased risk of pneumonia among immunocompetent, community dwelling older people. Findings of previous studies may reflect “healthy user” bias.

Use of proton pump inhibitors and H2 blockers and risk of pneumonia in older adults: a population-based case-control study

To examine whether use of proton pump inhibitors (PPIs) and H2 blockers is associated with increased pneumonia risk.