Background Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. Procedure We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls. Results Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4+ T cells were decreased (P = 0.022), while CD8+ T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8+ T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA. Conclusions Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development.

A number of studies have documented subjective improvement in somatic and psychological symptoms following breast reduction surgery. Objective data demonstrating improved postoperative function have been more difficult to assess, and particularly with respect to pulmonary function, the results have been contradictory. In this prospective study, patients completed a comprehensive preoperative questionnaire modified from the American Thoracic Society Division of Lung Diseases Epidemiology Standardization Project (1978). This questionnaire noted subjective pulmonary symptoms and pulmonary medical history. In addition, subjective symptoms related to breast size, including back and neck pain and shoulder pain and grooving, and a subjective evaluation of body image, were evaluated. All subjects received preoperative pulmonary function testing, including spirometry, lung volume measurements, and measurement of peak inspiratory and expiratory flow rates and pressures. Eight weeks after breast reduction, a repeat questionnaire and pulmonary function testing were administered. Preoperative and postoperative pulmonary function values were compared using Cochran-Mantel-Haenszel tests, and correlations were tested between changes in pulmonary function test values and subjective symptom improvement. Forty-four patients underwent an average of 2228-g bilateral reduction. All of these patients had their surgical procedures preauthorized as medically necessary by their insurance carriers. All subjective parameters examined were statistically significantly improved following breast reduction (p < 0.001). Of the 17 patients with preoperative complaints of shortness of breath, all noted significant improvement following breast reduction surgery (p < 0.001). Of the objective pulmonary criteria evaluated, inspiratory capacity, peak expiratory flow rate, and maximal voluntary ventilation showed a statistically significant improvement following surgery (p < 0.05). These changes correlated with body mass index; the greater the index, the greater the change in maximal voluntary ventilation and peak expiratory flow rate. Smokers in this group had the largest change in maximal voluntary ventilation (p < 0.008). No correlation could be found between preoperative pulmonary symptoms, a single subjective symptom, or grams of breast weight reduction and changes in pulmonary function tests. The results show that pulmonary parameters, related primarily to work of breathing (inspiratory capacity, maximal voluntary ventilation, peak expiratory flow rate), were statistically improved following breast reduction surgery, and these changes correlated with body mass index.

Background Fanconi Anemia (FA) is a rare genetic disorder resulting in a loss of function of the FA-related DNA repair pathway. Individuals with FA are predisposed to some cancers including oropharyngeal and gynecological cancers with known associations with human papillomavirus (HPV) in the general population. Since individuals with FA respond poorly to chemotherapy and radiation, prevention of cancer is critical. Methods To determine if individuals with FA are particularly susceptible to oral HPV infection, we analyzed survey-based risk factor data and tested DNA isolated from oral rinses from 126 individuals with FA and 162 unaffected first-degree family members for 37 HPV types. Results Fourteen individuals (11.1%) with FA tested positive, significantly more (p=0.003) than family members (2.5%). While HPV prevalence was even higher for sexually active individuals with FA (17.7% vs. 2.4% in family; p=0.003), HPV positivity also tended to be higher in the sexually inactive (8.7% in FA vs. 2.9% in siblings). Indeed, having FA increased HPV positivity 4.9 fold (95%CI: 1.6–15.4) considering age and sexual experience, but did not differ by other potential risk factors. Conclusion Our studies suggest that oral HPV is more common in individuals with FA. It will be essential to continue to explore associations between risk factors and immune dysfunction on HPV incidence and persistence over time. Impact HPV vaccination should be emphasized in those with FA as a first step to prevent oropharyngeal cancers, although additional studies are needed to determine if the level of protection it offers in this population is adequate.

BACKGROUND: Allergic disorders, including asthma, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis, and food allergy, are a major global health burden. The study and management of allergic disorders is complicated by the considerable heterogeneity in both the presentation and natural history of these disorders. Biorepositories serve as an excellent source of data and biospecimens for delineating subphenotypes of allergic disorders, but such resources are lacking. METHODS: In order to define subphenotypes of allergic disease accurately, we established an infrastructure to link and efficiently utilize clinical and epidemiologic data with biospecimens into a single biorepository called the Greater Cincinnati Pediatric Clinic Repository (GCPCR). Children with allergic disorders as well as healthy controls are followed longitudinally at hospital clinic, emergency department, and inpatient visits. Subjects' asthma, allergy, and skin symptoms; past medical, family, social, diet, and environmental histories; physical activity; medication adherence; perceived quality of life; and demographics are ascertained. DNA is collected from all participants, and other biospecimens such as blood, hair, and nasal epithelial cells are collected on a subset. RESULTS: To date, the GCPCR has 6,317 predominantly Caucasian and African American participants, and 93% have banked DNA. This large sample size supports adequately powered genetic, epidemiologic, environmental, and health disparities studies of childhood allergic diseases. CONCLUSIONS: The GCPCR is a unique biorepository that is continuously evaluated and refined to achieve and maintain rigorous clinical phenotype and biological data. Development of similar disease-specific repositories using common data elements is necessary to enable studies across multiple populations of comprehensively phenotyped patients.