Effect of annual influenza immunization on antibody response in lung transplant patients.

BACKGROUND: Influenza viral infections cause significant morbidity and mortality each season. Lung transplant patients may be at higher risk because of their underlying pathophysiology. Although annual immunization is the standard of care, its efficacy remains largely unproven. Previous studies showed poor antibody response to influenza vaccine in lung transplant patients, but no data on the antibody response in consecutive seasons have been published. METHODS: We studied antibody responses to influenza vaccine in 122 subjects: 66 lung transplant recipients, 28 control subjects, and 28 patients awaiting lung transplantation. We compared antibody response rates to individual viruses contained in influenza vaccines in consecutive years within the 3 groups. Serum antibody concentrations were measured at baseline and 2 to 4 weeks after vaccination by using the hemagglutination inhibition assay. Log-transformed antibody concentrations and incidence of serconversion and seroprotection were calculated. RESULTS: Median log-transformed antibody responses were similar in consecutive seasons in lung transplant subjects. Incidences of seroprotection and seroconversion did not differ between consecutive seasons in lung transplant recipients. CONCLUSIONS: Antibody responses were similar in consecutively measured years in lung transplant subjects. Annual influenza vaccination in lung transplant subjects produces similar immune responses in 2 consecutive years, indicating that these patients are not at significantly increased risk of vaccine failure.

Humoral immune responses to influenza vaccination in patients with obstructive sleep apnea.

STUDY OBJECTIVE: To compare humoral immune responses to influenza vaccination in subjects with obstructive sleep apnea (OSA) and in healthy volunteers (control subjects). DESIGN: Prospective, controlled, parallel-design study. SETTING: Sleep disorders center at a university hospital. SUBJECTS: Fourteen untreated subjects with moderate-to-severe OSA (apnea hypopnea index > 15 events/hr) and 17 healthy volunteers (control subjects). INTERVENTION: All subjects were given the influenza vaccine for the years 2004-2005 or 2005-2006. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained before and 2-4 weeks after vaccination to measure serum antibody titers for the A/New Caledonia/20/99 (H1N1)-like and B/Shanghai/361/2002-like viral strains by using the hemagglutination inhibition assay. Seroconversion was defined as an increase in the antibody titer by more than 4-fold, whereas seroprotection was defined as an antibody titer greater than 40 hemagglutination units. The mean +/- standard error of the mean apnea hypopnea index, calculated as the number of abnormal respiratory events divided by the number of hours of total sleep time, was 56 +/- 12 events/hour in the OSA group and 1.0 +/- 0.4 oxygen desaturations/hour in the control group (p<0.05). However, no significant differences were observed in changes in antibody concentration, frequencies of seroconversion, or rates of seroprotection between subjects with OSA and control subjects. Polysomnographic measures of OSA were not correlated with immune responses. CONCLUSION: Although pathophysiologic characteristics of OSA may influence immune responses, moderate-to-severe OSA did not impair humoral responses to the influenza vaccine in these subjects.

T-cell responses to hepatitis B surface antigen in lung transplant recipients.

STUDY OBJECTIVE: To determine whether lung transplant recipients would have a less vigorous T-cell response to hepatitis B surface antigen (HBsAg) than that of patients awaiting lung transplantation and healthy subjects, we sought to measure and compare T-cell responses among these three groups. DESIGN: Prospective study. SETTING: Lung transplant clinic at a university hospital. SUBJECTS: Twelve lung transplant recipients, 12 patients awaiting lung transplantation, and 15 healthy subjects. All participants had received the hepatitis B vaccine series and had a documented antibody response to it. INTERVENTION: Blood samples were obtained from each participant. MEASUREMENTS AND MAIN RESULTS: Participants' sex, age, time since lung transplantation (if applicable), and time since hepatitis B immunization were recorded. Peripheral blood mononuclear cells were isolated from the participants' blood samples for the trans vivo delayed-type hypersensitivity (DTH) assay. These cells were mixed with saline, tetanus toxoid, or HBsAg and injected into the footpads of immunodeficient mice. Resultant swelling of the footpad was used as an index of human T-cell response. The healthy subjects were younger than the patients in both transplant groups. However, we found no significant difference in DTH response elicited by HBsAg among the healthy subjects, patients awaiting lung transplantation, and lung transplant recipients (mean +/- standard error [SE] 34.7 +/- 4.3, 32.1 +/- 3.1, and 33.5 +/- 4.0 x 10(-4) in., respectively, p>0.8) or when tetanus toxoid was used as a positive control (15.7 +/- 2.8, 22.8 +/- 6.5, and 21.7 +/- 3.9 x 10(-4) in., respectively, p>0.3). No correlation between age or time since immunization and DTH response was noted. CONCLUSION: Lung transplant recipients maintained a T-cell response to HBsAg that was similar in vigor to that of both patients awaiting transplantation and healthy subjects even though their antibody concentrations waned rapidly after transplantation. The role of these T cells as a correlate of protection from infection remains to be investigated.

Tachycardia-induced heart failure does not alter myocardial P-glycoprotein expression.

STUDY OBJECTIVE: To determine the effects of tachycardia-induced heart failure on myocardial P-glycoprotein (P-gp) expression. DESIGN: Nonblinded, parallel, sham-controlled, animal model study. SETTING: University laboratory. ANIMALS: Thirty mongrel dogs. INTERVENTION: Heart failure was induced by rapid ventricular pacing over 4 weeks; sham procedures were performed for the control group. MEASUREMENTS AND MAIN RESULTS: Myocardial biopsies were taken from the left ventricular lateral wall and prepared for P-gp quantification by laser-induced fluorescence. The relative amount of P-gp messenger RNA (mRNA) was assessed by reverse transcriptase polymerase chain reaction. Rapid ventricular pacing produced heart failure and reduced the area ejection fraction from 48% +/- 6% to 21% +/- 6% (p<0.05 vs baseline). However, heart failure did not alter the quantity of myocardial P-gp (0.20 +/- 0.02 microg/ml for the control group vs 0.23 +/- 0.02 microg/ml for the intervention group, p=0.4). Furthermore, heart failure did not alter P-gp expression significantly. CONCLUSION: Myocardial P-gp does not change in response to tachycardia-induced heart failure. Thus, there is a low likelihood for P-gp-related drug resistance during a syndrome similar to tachycardia-induced heart failure.

Influence of intermittent hypoxia on myocardial and hepatic P-glycoprotein expression in a rodent model.

STUDY OBJECTIVE: Patients with obstructive sleep apnea who receive drug therapy for cardiovascular disease may experience resistant hypertension, arrhythmias, or more severe heart failure, and many of the drugs used to treat these conditions are substrates for P-glycoprotein (P-gp) transporters. Therefore, we sought to determine if intermittent hypoxia, which mimics obstructive sleep apnea, would upregulate myocardial and hepatic P-gp expression and Abcb1a and Abcb1b messenger RNA (mRNA) expression (genes that encode for P-gp) in an animal model. DESIGN: Prospective, randomized, blinded, parallel-design animal study. SETTING: University research laboratory. ANIMALS: Thirty adult, male Sprague-Dawley rats. INTERVENTION: Rats were assigned to either 2 weeks of intermittent hypoxia exposure similar to sleep apnea (12 rats) or no hypoxia exposure (controls, 18 rats). MEASUREMENTS AND MAIN RESULTS: After intermittent hypoxia or normoxia exposure, the rats were anesthetized. Heart and liver were harvested, and small samples were taken from the left ventricle (heart) and the liver for analysis. Expression of P-gp was measured by Western blotting, whereas Abcb1a and Abcb1b mRNA expression was assessed by real-time polymerase chain reaction. Band density of myocardial (but not hepatic) P-gp expression (standardized by beta-actin) was significantly higher in hypoxic rats than in control rats (p=0.03). Quantitative polymerase chain reaction revealed that myocardial and hepatic Abcb1a and myocardial Abcb1b mRNA expression were significantly increased in hypoxic rats compared with controls (p<0.05). CONCLUSION: Myocardial P-gp expression and myocardial and hepatic Abcb1a mRNA expression were significantly increased after 2 weeks of intermittent hypoxia. Hypoxia-induced increases in P-gp expression may partially explain drug-resistant cardiovascular disease in patients with obstructive sleep apnea.

Lung transplant patients' T cell responses to influenza vaccine viruses between seasons.

We hypothesized that T cell responses to influenza viruses by lung transplant and healthy individuals would be similar. Twelve lung transplant patients and 12 healthy individuals received influenza vaccines during two seasons. Lymphocytes were isolated for the trans-vivo delayed-type hypersensitivity assay from blood samples following immunization. T cell responses to all three inactivated influenza antigens from each were similar between the groups. However, the response to the A/New Caledonia (H1N1) virus by transplant patients was greater than the healthy controls' response, but only in the first season. The magnitude of the T cell responses in lung transplant patients is similar to those of healthy control individuals. These responses may be important in T cell memory.

Regional gap junction inhibition increases defibrillation thresholds.

It is clear that ischemia inhibits successful defibrillation by altering regional electro-physiology. However, the exact mechanisms are unclear. This study investigated whether regional gap junction inhibition increases biphasic shock defibrillation thresholds (DFT). Sixteen swine were instrumented with a mid-left anterior descending (LAD) perfusion catheter for regional infusion of 0.5 mM/h heptanol (n = 8) or saline (n = 8). DFT values and effective refractory periods (ERP) at five myocardial sites were determined. Regional conduction velocity (CV) was determined in an LAD drug-perfused and nondrug-perfused region in an additional seven swine. Regional heptanol infusion increased 50% DFT values by 33% (P = 0.01) and slowed CV by 42-59% (P < 0.01) but did not affect ERP. Regional heptanol also increased CV dispersion by approximately 270% (P < 0.05) but did not change ERP dispersion. Regional placebo did not alter any of these parameters. Furthermore, regional heptanol infusion induced spontaneous ventricular fibrillation in eight of eight animals. Increasing spatial conduction velocity dispersion by impairing regional gap junction conductance increased DFT values. Dispersion in conduction velocity slowing during regional ischemia may be an important determinant of defibrillation efficacy.