PROBLEM/CONDITION: Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema but has been defined recently as the physiologic finding of nonreversible pulmonary function impairment This surveillance summary reports trends in different measures of COPD during 1971-2000 REPORTING PERIOD COVERED: This report presents national data regarding objectively determined COPD (1971-1994); COPD-associated activity and functional limitations (1980-1996); self-reported COPD prevalence, COPD physician office and hospital outpatient department visits, COPD hospitalizations, and COPD deaths (1980-2000); and COPD emergency department visits (1992-2000) DESCRIPTION OF SYSTEMS: The Centers for Disease Control's National Center for Health Statistics conducts the National Health Interview Survey annually, which includes questions concerning COPD and activity limitations The National Center for Health Statistics collects physician office-visit data in the National Ambulatory Medical Care Survey, emergency department and hospital outpatient department data in the National Hospital Ambulatory Medical Care Survey, hospitalization data in the National Hospital Discharge Survey, and death data in the Mortality Component of the National Vital Statistics System Data regarding pulmonary function were obtained from the National Health and Nutrition Examination Surveys (NHANES) I (1971-1975) and III (1988-1994), and data regarding functional limitation were obtained from NHANES III, Phase 2 (1991-1994) RESULTS: During 2000, an estimated 10 million US adults reported physician-diagnosed COPD However, data from NHANES III estimate that approximately 24 million United States adults have evidence of impaired lung function, indicating that COPD is underdiagnosed During 2000, COPD was responsible for 8 million physician office and hospital outpatient visits, 15 million emergency department visits, 726,000 hospitalizations, and 119,000 deaths During the period analyzed, the most substantial change was the increase in the COPD death rate for women, from 201/100,000 in 1980 to 567/100,000 in 2000, compared with the more modest increase in the death rate for men, from 730/100,000 in 1980 to 826/100,000 in 2000 In 2000, for the first time, the number of women dying from COPD surpassed the number of men dying from COPD (59,936 vs 59,118) Another substantial change observed is that the proportion of the population aged < 55 years with mild or moderate COPD, on the basis of pulmonary function testing, decreased from 1971-1975 to 1988-1994, possibly indicating that the upward trends in COPD hospitalizations and mortality might not continue INTERPRETATION: COPD is a major cause of morbidity, mortality, and disability in the US Despite its ease of diagnosis, COPD remains an underdiagnosed disease, chiefly in its milder and more treatable form

Chronic obstructive pulmonary disease surveillance--United States, 1971-2000.

We performed a longitudinal analysis of antibody titers specific for viral antigens (vaccinia, measles, mumps, rubella, varicella–zoster virus, and Epstein–Barr virus) and nonreplicating antigens (tetanus and diphtheria) in 45 subjects for a period of up to 26 years. In addition, we measured antigen-specific memory B cells by means of limiting-dilution analysis, and we compared memory B-cell frequencies to their corresponding serum antibody levels. Results Antiviral antibody responses were remarkably stable, with half-lives ranging from an estimated 50 years for varicella–zoster virus to more than 200 years for other viruses such as measles and mumps. Antibody responses against tetanus and diphtheria antigens waned more quickly, with estimated half-lives of 11 years and 19 years, respectively. B-cell memory was long-lived, but there was no significant correlation between peripheral memory B-cell numbers and antibody levels for five of the eight antigens tested. Conclusions These studies provide quantitative analysis of serologic memory for multiple antigens in subjects followed longitudinally over the course of more than one decade. In cases in which multiple exposures or repeated vaccinations were common, memory B-cell numbers did not correlate with antibody titers. This finding suggests that peripheral memory B cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of protective immunity.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa066092

Duration of humoral immunity to common viral and vaccine antigens.

The biological differences associated with the sex of an individual are a major source of variation, affecting immune responses to vaccination. Compelling clinical data illustrate that men and women differ in their innate, humoral, and cell-mediated responses to viral vaccines. Sex affects the frequency and severity of adverse effects of vaccination, including fever, pain, and inflammation. Pregnancy can also substantially alter immune responses to vaccines. Data from clinical trials and animal models of vaccine efficacy lay the groundwork for future studies aimed at identifying the biological mechanisms that underlie sex-specific responses to vaccines, including genetic and hormonal factors. An understanding and appreciation of the effect of sex and pregnancy on immune responses might change the strategies used by public health officials to start efficient vaccination programmes (optimising the timing and dose of the vaccine so that the maximum number of people are immunised), ensure sufficient levels of immune responses, minimise adverse effects, and allow for more efficient protection of populations that are high priority (eg, pregnant women and individuals with comorbid conditions).

/pdf/the-xs-and-y-of-immune-responses-to-viral-vaccines-2olfe786kn.pdf

The Xs and Y of immune responses to viral vaccines

There is substantial variation between individuals in the immune response to vaccination. In this review, we provide an overview of the plethora of studies that have investigated factors that influence humoral and cellular vaccine responses in humans. These include intrinsic host factors (such as age, sex, genetics, and comorbidities), perinatal factors (such as gestational age, birth weight, feeding method, and maternal factors), and extrinsic factors (such as preexisting immunity, microbiota, infections, and antibiotics). Further, environmental factors (such as geographic location, season, family size, and toxins), behavioral factors (such as smoking, alcohol consumption, exercise, and sleep), and nutritional factors (such as body mass index, micronutrients, and enteropathy) also influence how individuals respond to vaccines. Moreover, vaccine factors (such as vaccine type, product, adjuvant, and dose) and administration factors (schedule, site, route, time of vaccination, and coadministered vaccines and other drugs) are also important. An understanding of all these factors and their impacts in the design of vaccine studies and decisions on vaccination schedules offers ways to improve vaccine immunogenicity and efficacy.

Factors That Influence the Immune Response to Vaccination

Do men die young and sick, or do women live long and healthy? By trying to explain the sexual dimorphism in life expectancy, both biological and environmental aspects are presently being addressed. Besides age-related changes, both the immune and the endocrine system exhibit significant sex-specific differences. This review deals with the aging immune system and its interplay with sex steroid hormones. Together, they impact on the etiopathology of many infectious diseases, which are still the major causes of morbidity and mortality in people at old age. Among men, susceptibilities toward many infectious diseases and the corresponding mortality rates are higher. Responses to various types of vaccination are often higher among women thereby also mounting stronger humoral responses. Women appear immune-privileged. The major sex steroid hormones exhibit opposing effects on cells of both the adaptive and the innate immune system: estradiol being mainly enhancing, testosterone by and large suppressive. However, levels of sex hormones change with age. At menopause transition, dropping estradiol potentially enhances immunosenescence effects posing postmenopausal women at additional, yet specific risks. Conclusively during aging, interventions, which distinctively consider the changing level of individual hormones, shall provide potent options in maintaining optimal immune functions.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.12326

How sex and age affect immune responses, susceptibility to infections, and response to vaccination

ChimeriVax-JE is a live, attenuated vaccine against Japanese encephalitis, using yellow fever (YF) 17D vaccine as a vector. In a double-blind phase 2 trial, 99 adults received vaccine, placebo, or YF 17D vaccine (YF-VAX). ChimeriVax-JE was well tolerated, with no differences in adverse events between treatment groups. Viremias resulting from administration of ChimeriVax-JE and YF-VAX were of short duration and low titer; 82 (94%) of 87 subjects administered graded doses (1.8-5.8 log(10)) of ChimeriVax-JE developed neutralizing antibodies. A second dose, administered 30 days later, had no booster effect. Previous inoculation with YF did not interfere with ChimeriVax-JE, but there was a suggestion (not statistically significant) that ChimeriVax-JE interfered with YF-VAX administered 30 days later. A separate study explored immunological memory both in subjects who had received ChimeriVax-JE 9 months before and in ChimeriVax-JE-naive subjects challenged with inactivated mouse-brain vaccine (JE-VAX). Anamnestic responses were observed in preimmune individuals. ChimeriVax-JE appears to be a safe vaccine that provides protective levels of neutralizing antibody after a single dose.

Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen.

Safety and efficacy of E. coli enterotoxin adjuvant for urease-based rectal immunization against Helicobacter pylori

Yellow fever (YF) is a significant health problem in South America and Africa. Travelers to these areas require immunization. The United States, infested with Aedes aegypti mosquitoes, is at risk of introduction of this disease. There is only a single U.S. manufacturer of YF 17D vaccine, and supplies may be insufficient in an emergency. A randomized, double-blind outpatient study was conducted in 1,440 healthy individuals, half of whom received the U.S. vaccine (YF-VAX) and half the vaccine manufactured in the United Kingdom (ARILVAX). A randomly selected subset of approximately 310 individuals in each treatment group was tested for YF neutralizing antibodies 30 days after vaccination. The primary efficacy endpoint was the proportion of individuals who developed a log neutralization index (LNI) of 0.7 or higher. Seroconversion occurred in 98.6% of individuals in the ARILVAX group and 99.3% of those in the YF-VAX group. Statistically, ARILVAX was equivalent to YF-VAX (P = .001). Both vaccines elicited mean antibody responses well above the minimal level (LNI 0.7) protective against wild-type YF virus. The mean LNI in the YF-VAX group was higher (2.21) than in the ARILVAX group (2.06; P = .010) possibly because of the higher dose contained in YF-VAX. Male gender, Caucasian race, and smoking were associated with higher antibody responses. Both vaccines were well tolerated. Overall, the treatment groups were comparable with respect to safety except that individuals in the ARILVAX group experienced significantly less edema, inflammation, and pain at the injection site than those in the YF-VAX group. No serious adverse events were attributable to either vaccine. YF-VAX participants (71.9%) experienced one or more nonserious adverse events than ARILVAX individuals (65.3%; P = .008). The difference was due to a higher rate of injection site reactions in the YF-VAX group. Mild systemic reactions (headache, myalgia, malaise, asthenia) occurred in roughly 10% to 30% of participants during the first few days after vaccination, with no significant difference across treatment groups. Adverse events were less frequent in individuals with preexisting immunity to YF, indicating a relationship to virus replication.

Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial

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Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen.

Safety and efficacy of E. coli enterotoxin adjuvant for urease-based rectal immunization against Helicobacter pylori

Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX and YF-VAX) in a phase III multicenter, double-blind clinical trial