Global quality of life and mortality risk in patients with cancer: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to examine the impact of global quality of life (QOL) on mortality risk in patients with cancer, considering cancer type and timepoint of QOL assessment. METHODS: A systematic search was conducted using Cumulated Index to Nursing and Allied Health Literature, PubMed/MEDLINE, and Scopus databases from inception to December 2022. Observational studies that assessed QOL and examined mortality risk in patients with cancer were extracted. Subgroup analyses were performed for cancer types and timepoints of QOL assessment. RESULTS: Overall, global QOL was significantly associated with mortality risk (hazard ratio: 1.06, 95% confidence interval: 1.05-1.07; p < 0.00001). A subgroup analysis based on cancer type demonstrated that lung, head and neck, breast, esophagus, colon, prostate, hematologic, liver, gynecologic, stomach, brain, bladder, bone and soft tissue, and mixed type cancers were significantly associated with mortality risk; however, melanoma and pancreatic cancer were not significantly associated with mortality risk. Additionally, global QOL was associated with mortality risk at all timepoints (pretreatment, posttreatment, and palliative phase); pretreatment QOL had the largest impact, followed by posttreatment QOL. CONCLUSION: These findings provide evidence that QOL is associated with mortality risk in patients with cancer at any timepoint. These results indicate the importance of evaluating the QOL and supportive interventions to improve QOL in any phase.

Impact of quality of life on mortality risk in patients with esophageal cancer: a systematic review and meta-analysis.

This systematic review and meta-analysis investigated the impact of quality of life (QoL) on mortality risk in patients with esophageal cancer. A literature search was conducted using the CINAHL, PubMed/MEDLINE, and Scopus databases for articles published from inception to December 2022. Observational studies that examined the association between QoL and mortality risk in patients with esophageal cancer were included. Subgroup analyses were performed for time points of QoL assessment and for types of treatment. Seven studies were included in the final analysis. Overall, global QoL was significantly associated with mortality risk (hazard ratio 1.02, 95% confidence interval 1.01-1.04; p < 0.00004). Among the QoL subscales of QoL, physical, emotional, role, cognitive, and social QoL were significantly associated with mortality risk. A subgroup analysis by timepoints of QoL assessment demonstrated that pre- and posttreatment global and physical, pretreatment role, and posttreatment cognitive QoL were significantly associated with mortality risk. Moreover, another subgroup analysis by types of treatment demonstrated that the role QoL in patients with surgery, and the global, physical, role, and social QoL in those with other treatments were significantly associated with mortality risk. These findings indicate that the assessment of QoL in patients with esophageal cancer before and after treatment not only provides information on patients' condition at the time of treatment but may also serve as an outcome for predicting life expectancy. Therefore, it is important to conduct regular QoL assessments and take a proactive approach to improve QoL based on the results of these assessments.

Pretreatment quality of life and survival in patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: Although many studies have explored the correlation between quality of life and survival, none have reported this relationship for specific cancers assessed at distinct time points. This meta-analysis aimed to investigate the impact of pretreatment Global Quality of Life (QOL) and functioning QOL, including physical, social, role, emotional, and cognitive QOLs, on mortality risk in patients with lung cancer. METHODS: A literature search was conducted across the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PubMed databases for articles published between their inception and December 2022. Subsequently, 11 studies were selected based on predefined eligibility criteria to investigate the relationship between pretreatment QOLs and mortality risk in patients with lung cancer. RESULTS: Pretreatment global, physical, social, role, and emotional QOLs were significantly associated with mortality risk as follows: Global QOL (hazard ratio [HR] = 1.08 95% confidence interval [CI] = 1.03-1.13); Physical QOL (HR = 1.04 95% CI = 1.02-1.05); Social QOL (HR = 1.02 95% CI = 1.01-1.03; Role QOL (HR = 1.01 95% CI = 1.01-1.02); Emotional QOL (HR = 1.01 95% CI = 1.00-1.03). CONCLUSIONS: These findings underscore the importance of early QOL assessment after diagnosis as well as early provision of physical, social, and psychological support accommodating each patient's demands. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number CRD42023398206, Registered on February 20, 2023.

Association between quality of life and mortality risk in patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with breast cancer present with various problems that have an adverse effect on the quality of life (QOL). However, the association between the QOL and mortality among patients with breast cancer remains controversial. Therefore, this systematic review and meta-analysis aimed to determine whether QOL impacts prognosis in patients with breast cancer. METHODS: The databases of CINAHL, Scopus, and PubMed databases were searched to retrieve observational studies that assessed the QOL and mortality risk in patients with breast cancer published before December 2022. RESULTS: Among the 119,061 articles retrieved, six observational studies were included in the meta-analysis. Physical QOL (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01-1.07, p = 0.003), emotional QOL (HR: 1.01, 95% CI: 1.00-1.03, p = 0.05), and role QOL (HR: 1.01, 95% CI: 1.00-1.01, p = 0.007) showed significant associations with mortality risk. In contrast, global QOL, cognitive QOL, and social QOL showed no associations with mortality risk. Subgroup analysis performed according to treatment time points revealed that the post-treatment physical QOL was associated with mortality risk. CONCLUSIONS: Physical QOL, emotional QOL, and role QOL are associated with mortality risk in patients with breast cancer. Furthermore, post-treatment physical QOL showed a more significant association with prolonged survival than pre-treatment physical QOL.

Neurological Outcomes of Chemotherapy-Induced Peripheral Neuropathy in Patients With Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine whether chemotherapy-induced peripheral neuropathy (CIPN) affects the risk of falls and physical function in patients with cancer. METHODS: A literature search was conducted in the CINAHL, Scopus, and PubMed databases for articles published from January 1950 to April 2022. Seven review authors retrieved studies using predetermined eligibility criteria, extracted the data, and evaluated the quality. RESULTS: Nine studies were included in the analysis. Patients with CIPN had a significantly higher risk of falls than those without CIPN (risk ratio = 1.38, 95% confidence interval [CI] =1.18-1.62). Patients with CIPN had lower grip strength (standardized mean difference [SMD] =-0.42, 95% CIs = -0.70 to -0.14, P = .003), longer chair stand time (SMD = 0.56, 95% CIs = -0.01 to 1.17, P = .05), worse timed up and go test time (SMD = 0.79, 95% CIs = 0.41 to 1.17, P < .0001), and lower mean Fullerton Advanced Balance scale score (SMD = -0.81, 95% CIs = -1.27 to -0.36, P = .005) than patients without CIPN. There were no significant differences in gait speed (P = .38) or Activities-specific Balance Confidence Scale score (P = .09) between patients with and without CIPN. CONCLUSIONS: This systematic review and meta-analysis demonstrated that patients with CIPN are prone to falls and impaired balance function and muscle strength.

Recent Findings in Physical Exercise for Cancer Survivors.

In recent years, the number of cancer survivors has been increasing each year due to advances in the early diagnosis and treatment of cancer. Cancer survivors present a variety of physical and psychological complications due to cancer and its treatment. Physical exercise is an effective nonpharmacological treatment for complications in cancer survivors. Furthermore, recent evidence has shown that physical exercise improves the prognosis of cancer survivors. The benefits of physical exercise have been widely reported, and guidelines for physical exercise for cancer survivors have been published. These guidelines recommend that cancer survivors engage in moderate- or vigorous-intensity aerobic exercises and/or resistance training. However, many cancer survivors have a poor commitment to physical exercise. In the future, it is necessary to promote physical exercise among cancer survivors through outpatient rehabilitation and community support.

Impact of Physical Inactivity on the Risk of Disability and Hospitalization in Older Patients with Advanced Lung Cancer.

PURPOSE: This prospective observational study aimed to explore the influence of physical inactivity during initial chemotherapy on the risk of disability and hospitalization in later life among older patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged 70 or above who were scheduled to receive first-line chemotherapy for newly diagnosed advanced NSCLC were recruited for the study. An electronic pedometer was used to measure daily steps; based on the change rate (cutoff: -12.5%) from pretreatment to 12 ± 4 weeks after enrolment, patients were classified as active or inactive. The Barthel Index estimated activities of daily living. We compared disability-free survival time, mean cumulative functions of hospital stays, and medical costs, between the active and inactive groups. RESULTS: Among the 29 patients enrolled, 21 were evaluable. Compared with active patients (n = 11), inactive patients (n = 10) showed shorter disability-free survival (6.4 vs 19.9 months, p < 0.05) and tended to have longer hospital stays (23.7 vs 6.3 days/person) and higher inpatient care cost (¥1.6 vs ¥0.3 million/person [US$16,000 vs US$3000/person]) during the first year. CONCLUSION: Physical inactivity during initial chemotherapy may be a risk factor for developing disability and requiring hospitalization in later life for older patients with advanced NSCLC. Our findings may indicate the need for lifestyle interventions with multidisciplinary teams, which include physicians, nurses, and physiotherapists, for older patients with advanced lung cancer during an active cancer treatment. A large-sample-sized study is needed to validate our findings.

Days Spent at Home near the End of Life in Japanese Elderly Patients with Lung Cancer: Post hoc Analysis of A Prospective Study.

OBJECTIVE: Days spent at home (DASH) near the end of life is considered an important patient-centered goal and outcome because many patients want to stay at home toward the end of life. This study aimed to estimate the individual DASH near the end of life and identify its early predictors, including muscle mass and physical function, among elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We conducted a post hoc analysis of the prospective observational study (UMIN000009768) that recruited patients aged ≥ 70 years who were scheduled to undergo first-line chemotherapy because of advanced NSCLC. We measured the muscle mass by bioelectrical impedance analysis at baseline. DASH was calculated as 30 days minus the number of days spent in hospitals, palliative care facilities, or nursing homes during the last 30 days of life. We performed linear regression analyses to evaluate the predictors of DASH. RESULTS: Altogether, 16 women and 28 men with a median overall survival of 15.5 months (range: 2.9-58.9) were included. The median DASH in the last 30 days of life was 8 days (range: 0-30, interquartile range: 0-23). Men had longer DASH than women by 7.3 days. Patients who had good trunk muscle mass index and hand-grip strength had significantly longer DASH than those who did not (4.7 days per kg/m2 increase [P = 0.017] and 0.4 days per kg increase [P = 0.032], respectively). CONCLUSIONS: Most elderly patients with advanced NSCLC had a limited DASH near the end of life. The risk factors for reduced DASH were women, reduced muscle mass, and poor physical function at the time of diagnosis of advanced NSCLC. Our findings would encourage early discussions about end-of-life care for patients with advanced cancers with risk factors for short DASH at the time of diagnosis, and thus, improve the quality of end-of-life care.

Clinical impact of walking capacity on the risk of disability and hospitalizations among elderly patients with advanced lung cancer.

PURPOSE: Little is known about the impact of decreased walking capacity on clinical outcomes in elderly patients with cancer. This prospective observational study aimed to investigate the impact of walking capacity on the risk of disability and hospitalization in elderly patients with advanced lung cancer. METHOD: This study prospectively enrolled 60 patients aged ≥ 70 years with advanced non-small-cell lung cancer (NSCLC) scheduled to receive first-line chemotherapy or radical radiotherapy between January 2013 and December 2014 (trial registration number: UMIN000009768). Patients were classified into the mobile or less mobile group based on the median incremental shuttle walking distance (ISWD) before initial treatment. Assessments included the Barthel index, disability-free survival time, mean cumulative lengths of hospital stay, and inpatient medical costs. RESULTS: The median ISWD was 290 m (interquartile range, 245-357.5 m). The mobile group (ISWD ≥ 290 m) had a longer disability-free survival time than the less mobile group (ISWD < 290 m, 24.6 months vs. 8.4 months, p < 0.05). During the first year from study entry, the mobile group had shorter cumulative lengths of hospital stay (41.3 vs. 72.9 days/person, p < 0.05) and lower inpatient medical costs (¥1.9 vs. ¥2.9 million/person, p < 0.05) than the less mobile group. CONCLUSION: Elderly NSCLC patients with adequate walking capacity showed lower risks of disability, shorter hospitalizations, and lower inpatient medical costs than patients with reduced walking capacity. Further prospective research is needed to validate these findings. The trial was registered with the University Hospital Medical Information Network as trial number UMIN000009768 on January 13, 2013. TRIAL REGISTRATION: UMIN000009768.

A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol.

BACKGROUND: Most advanced elderly cancer patients experience fatigue, anorexia, and declining physical function due to cancer cachexia, for which effective interventions have not been established. We performed a phase I study of a new nonpharmacological multimodal intervention called the nutritional and exercise treatment for advanced cancer (NEXTAC) program and reported the excellent feasibility of and compliance with this program in elderly patients with advanced cancer who were at risk for cancer cachexia. We report here the background, hypothesis, and design of the next-step multicenter, randomized phase II study to evaluate the efficacy of the program, the NEXTAC-TWO study. METHODS: Patients with chemo-naïve advanced non-small cell lung cancer or pancreatic cancer, age ≥ 70 years, performance status ≤2, with adequate organ function and without disability according to the modified Katz index will be eligible. In total, 130 participants will be recruited from 15 Japanese institutions and will be randomized into either the intervention group or a control group. Computer-generated random numbers are allocated to each participant. Stratification factors include performance status (0 to 1 vs. 2), site of primary cancer (lung vs. pancreas), stage (III vs. IV), and type of chemotherapy (cytotoxic vs. others). Interventions and assessment will be performed 4 times every 4 ± 2 weeks from the date of randomization. Interventions will consist of nutritional counseling, nutritional supplements (rich in branched-chain amino acids), and a home-based exercise program. The exercise program will include low-intensity daily muscle training and lifestyle education to promote physical activity. The primary endpoint is disability-free survival. It is defined as the period from the date of randomization to the date of developing disability or death due to any cause. This trial also plans to evaluate the improvements in nutritional status, physical condition, quality of life, activities of daily living, overall survival, and safety as secondary endpoints. Enrollment began in August 2017. The study results will demonstrate the efficacy of multimodal interventions for elderly cancer patients and their application for the maintenance of physical and nutritional conditions in patients with cancer cachexia. This work is supported by a grant-in-aid from the Japan Agency for Medical Research and Development. DISCUSSION: This is the first randomized trial to evaluate the efficacy and safety of a multimodal intervention specific for elderly patients with advanced cancer. TRIAL REGISTRATION: Registered at August 23, 2017. Registry number: UMIN000028801 .

Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer.

BACKGROUND: Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme. METHODS: This was a multicentre prospective single-arm study. We recruited 30 of 46 screened patients aged ≥70 years scheduled to receive first-line chemotherapy for newly diagnosed, advanced pancreatic, or non-small-cell lung cancer. Physical activity was measured using pedometers/accelerometer (Lifecorder® , Suzuken Co., Ltd., Japan). An 8 week educational intervention comprised three exercise and three nutritional sessions. The exercise interventions combined home-based low-intensity resistance training and counselling to promote physical activity. Nutritional interventions included standard nutritional counselling and instruction on how to manage symptoms that interfere with patient's appetite and oral intake. Supplements rich in branched-chain amino acids (Inner Power® , Otsuka Pharmaceutical Co., Ltd., Japan) were provided. The primary endpoint of the study was feasibility, which was defined as the proportion of patients attending ≥4 of six sessions. Secondary endpoints included compliance and safety. RESULTS: The median patient age was 75 years (range, 70-84). Twelve patients (40%) were cachectic at baseline. Twenty-nine patients attended ≥4 of the six planned sessions (96.7%, 95% confidence interval, 83.3 to 99.4). One patient dropped out due to deteriorating health status. The median proportion of days of compliance with supplement consumption and exercise performance were 99% and 91%, respectively. Adverse events possibly related to the NEXTAC programme were observed in five patients and included muscle pain (Grade 1 in two patients), arthralgia (Grade 1 in one patient), dyspnoea on exertion (Grade 1 in one patient), and plantar aponeurositis (Grade 1 in one patient). CONCLUSIONS: The early induction of multimodal interventions showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non-small-cell lung cancer receiving concurrent chemotherapy. We are now conducting a randomized phase II study to measure the impact of these interventions on functional prognosis.

Promotion of Behavioral Change and the Impact on Quality of Life in Elderly Patients with Advanced Cancer: A Physical Activity Intervention of the Multimodal Nutrition and Exercise Treatment for Advanced Cancer Program.

OBJECTIVE: Physical activity (PA) may improve the quality of life (QOL) of cancer survivors. However, the impact on patients with advanced cancer with high cachectic potential is unknown. We analyzed the feasibility of PA intervention using the multimodal program Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) and the impact on QOL in elderly patients with advanced cancer. METHODS: We recruited 30 patients aged ≥70 years who were scheduled to receive the first-line chemotherapy for newly diagnosed advanced pancreatic or non-small-cell lung cancer. The QOL was assessed using the European Organization for Research and Treatment of Cancer QOL Questionnaire version 3.0, while the PA was measured using a pedometer/accelerometer. Instructors counseled patients to increase daily activity in an 8-week educational intervention. We assessed patient attendance, compliance, and intervention efficacy. RESULTS: The median patients' age was 75 years (range, 70-84 years). Twelve patients (40%) were cachectic at baseline. Twenty-eight (93%) patients attended all sessions. Six (21%) and 15 (52%) patients increased their indoor and outdoor activity, respectively. There were significant differences in measured PA, global QOL, and role and emotional functioning between the patients who increased outdoor activity and those who did not. CONCLUSIONS: The PA intervention of the NEXTAC program was feasible as the elderly patients with advanced cancer in this study were highly compliant. The majority of patients demonstrated behavioral changes that were associated with the improvement in global QOL. We conduct a randomized phase II study to measure the impact of the NEXTAC program on QOL and functional prognosis.

Impact of Cancer Cachexia on Hospitalization-associated Physical Inactivity in Elderly Patients with Advanced Non-small-cell Lung Cancer.

OBJECTIVE: New or worsening disability can develop in elderly patients in just 1 week of hospitalization for acute illness. Elderly patients with cancer, particularly those with cancer cachexia, are vulnerable to disability. This study aimed to explore the impact of hospitalization and cachexia on physical activity (PA) in elderly patients during chemotherapy. METHODS: We prospectively enrolled 18 patients aged ≥70 years with newly-diagnosed, advanced non-small-cell lung cancer scheduled to initiate first-line chemotherapy. PA was measured using an accelerometer (Lifecorder®, Suzuken Co., Ltd., Japan). Mean daily steps at baseline, during hospitalization, and subsequent weeks (1st, 2nd, and 3rd week after discharge) were compared. RESULTS: A total of 30 hospitalizations for chemotherapy were evaluated in 18 patients with a median age of 74.5 years. The median number of baseline daily steps was 3756. Fifteen cases (50%) showed fewer daily steps during hospitalization and no recovery to baseline level during the 1st week after discharge. Long hospitalizations (≥8 days) and the presence of cachexia were associated with persistent physical inactivity. One patient developed disability within 30 days after hospitalization. CONCLUSIONS: Physical inactivity was frequently seen after hospitalization for chemotherapy in elderly patients with advanced lung cancer. Longer in-hospital days and the presence of cancer cachexia caused slow recovery from physical inactivity. Individualized hospitalization planning based on careful consideration of patient age and the presence of cancer cachexia may be needed to prevent physical inactivity and disability.

Unfavorable impact of cancer cachexia on activity of daily living and need for inpatient care in elderly patients with advanced non-small-cell lung cancer in Japan: a prospective longitudinal observational study.

BACKGROUND: Cancer cachexia in elderly patients may substantially impact physical function and medical dependency. The aim of this study was to estimate the impact of cachexia on activity of daily living (ADL), length of hospital stay, and inpatient medical costs among elderly patients with advanced non-small-cell lung cancer (NSCLC) receiving chemotherapy. METHODS: Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to receive first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. ADL was assessed using the Barthel index. The disability-free survival time (DFS) was calculated as the time between the date of study entry and the date of onset of a disabling event, which was defined as a 10-point decrease in the Barthel index from that at baseline. The mean cumulative function of the length of hospital stay and inpatient medical costs (¥, Japanese yen) was calculated. RESULTS: The study patients comprised 11 women and 19 men, with a median age of 74 (range, 70-82) years. Cachexia was diagnosed in 19 (63%) patients. Cachectic patients had a shorter DFS (7.5 vs. 17.1 months, p < 0.05). During the first year from study entry, cachectic patients had longer cumulative lengths of hospital stay (80.7 vs. 38.5 days/person, p < 0.05), more frequent unplanned hospital visits or hospitalizations (4.2 vs. 1.7 times/person, p < 0.05), and higher inpatient medical costs (¥3.5 vs. ¥2.1 million/person, p < 0.05) than non-cachectic patients. CONCLUSIONS: Elderly NSCLC patients with cachexia showed higher risks for disability, prolonged hospitalizations, and higher inpatient medical costs while receiving chemotherapy than patients without cachexia. Our results might indicate that there is a potential need for an early intervention to minimize progression to or development of cachexia, improve functional prognosis, and reduce healthcare resource burden in this population. TRIAL REGISTRATION: Trial registration number: UMIN000009768 . Name of registry: UMIN (University hospital Medical Information Network). Date of registration: 14 January 2013. Date of enrolment of the first participant to the trial: 23 January 2013.

Skeletal muscle depletion during chemotherapy has a large impact on physical function in elderly Japanese patients with advanced non-small-cell lung cancer.

BACKGROUND: Elderly patient with advanced cancer is one of the most vulnerable populations. Skeletal muscle depletion during chemotherapy may have substantial impact on their physical function. However, there is little information about a direct relationship between quantity of muscle and physical function. We sought to explore the quantitative association between skeletal muscle depletion, and muscle strength and walking capacity in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to initiate first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. Lumbar skeletal muscle index (LSMI, cm2/m2), incremental shuttle walking distance (ISWD, m), and hand-grip strength (HGS, kg) were assessed at baseline, and 6 ± 2 weeks (T2) and 12 ± 4 weeks (T3) after study enrollment. Associations were analyzed using linear regression. RESULTS: Altogether, 11 women and 19 men with a median age of 74 (range, 70-82) years were included in the study; 24 received cytotoxic chemotherapy and 6, gefitinib. Mean ± standard deviation of LSMI, ISWD and HGS were 41.2 ± 7.8 cm2/m2, 326.0 ± 127.9 m, and 29.3 ± 8.5 kg, respectively. LSMI and ISWD significantly declined from baseline to T2 and T3. HGS significantly declined from baseline to T2 and T3 only in men. Change in LSMI was significantly associated with change in HGS (ß = 0.3 ± 0.1, p = 0.0127) and ISWD (ß = 8.8 ± 2.4, p = 0.0005). CONCLUSIONS: Skeletal muscle depletion accompanied with physical functional decline started in the early phase of the chemotherapy in elderly patients with advanced NSCLC. Our results suggest that there may be a need for early supportive care in these patients to prevent functional decline during chemotherapy. TRIAL REGISTRATION: Trial registration number: UMIN000009768 Name of registry: UMIN (University hospital Medical Information Network). URL of registry: Date of registration: 14 January 2013. Date of enrolment of the first participant to the trial: 23 January 2013.

Food allergens inducing a lymphocyte-mediated immunological reaction in canine atopic-like dermatitis.

Canine atopic-like dermatitis (ALD) is suspected to be associated with food allergies, particularly those mediated by lymphocytes. In this study, 54 cases were included as ALD dogs, based on the negative IgE test results. In the dogs, the percentage of activated cells in helper-T lymphocytes was measured by flow cytometry using cultured peripheral lymphocytes under food allergen stimulation. We observed that 49 of the 54 ALD dogs (90.7%) had positive lymphocyte reactions against one or more food allergens. The most common food allergen was soybean, showing positive results in 21 dogs (42.9%), while the allergen to cause the lowest number of reactions was catfish (only 5 dogs, 10.2%). These results may be useful in considering elimination diets for ALD dogs.

Flow cytometric analysis of lymphocyte proliferative responses to food allergens in dogs with food allergy.

Two different allergy tests, antigen-specific immunoglobulin E quantification (IgE test) and flow cytometric analysis of antigen-specific proliferation of peripheral lymphocytes (lymphocyte proliferation test), were performed to examine differences in allergic reactions to food allergens in dogs with food allergy (FA). Thirteen dogs were diagnosed as FA based on clinical findings and elimination diet trials. Seven dogs clinically diagnosed with canine atopic dermatitis (CAD) were used as a disease control group, and 5 healthy dogs were used as a negative control group. In the FA group, 19 and 33 allergen reactions were identified using the serum IgE test and the lymphocyte proliferation test, respectively. Likewise, in the CAD group, 12 and 6 allergen reactions and in the healthy dogs 3 and 0 allergen reactions were identified by each test, respectively. A significant difference was found between FA and healthy dogs in terms of positive allergen detection by the lymphocyte proliferation test, suggesting that the test can be useful to differentiate FA from healthy dogs but not from CAD. Both tests were repeated in 6 of the dogs with FA after a 1.5- to 5-month elimination diet trial. The IgE concentrations in 9 of 11 of the positive reactions decreased by 20-80%, whereas all the positive reactions in the lymphocyte proliferation test decreased to nearly zero (P<0.05), suggesting that lymphocytes against food allergens may be involved in the pathogenesis of canine FA.

Establishment of a quantitative ELISA for the measurement of allergen-specific IgE in dogs using anti-IgE antibody cross-reactive to mouse and dog IgE.

As IgE plays a pivotal role in type I hypersensitivity-mediated allergic diseases, it is valuable to measure absolute quantity of serum antigen-specific IgE for clinical and research purposes. Here we describe a novel ELISA system that enables quantification of antigen-specific IgE in ng/ml in dogs. A newly developed monoclonal antibody (CRE-DM) was shown to recognize canine and mouse IgE equally in a dose dependent manner, but it did not recognize canine IgG. The reactivity of CRE-DM to canine IgE was also confirmed by an inhibition ELISA using canine IgE as an inhibitor and the maximum inhibition rate was 91.3%. In order to know whether canine IgE specific to an allergen could be quantitatively measured with an ELISA using CRE-DM, we established a quantitative ELISA that could measure canine IgE recognizing Cry j 1, one of the major allergens of Japanese cedar pollen. In this ELISA, a standard curve was created by using concentration-predetermined Cry j 1-specific monoclonal mouse IgE. According to the standard curve, the concentration of Cry j 1-specific IgE in dogs that were experimentally sensitized to Japanese cedar pollen could be calculated and determined in ng/ml. The specificity of the Cry j 1-specific IgE ELISA using CRE-DM was also confirmed by inhibition ELISA using canine IgE as an inhibitor and the inhibition rate was 97.0%. Reproducibility of the ELISA in three independent assays was determined using groups of pooled canine sera whose Cry j 1-IgE titers ranged from 155.9 to 888.2 ng/ml. Intra- and inter-assay reproducibility was determined with coefficient of variation ranging between 3.1-5.2% and 2.2-8.0%, respectively. These results demonstrated that the ELISA utilizing CRE-DM was a specific, reliable and robust new laboratory test that could quantify absolute amount of antigen-specific IgE in canine serum. The ELISA will serve as a useful tool in the clinics to evaluate the change of serum IgE titers during anti-allergic treatments as well as during seasonal fluctuation of allergen exposure.