Amrita Dosanjh

Coccidioidomycosis and lung transplantation.

Coccidioidomycosis, an endemic fungal infection in the desert southwestern United States, causes substantial morbidity and mortality in immunocompromised hosts. Because lungs are the primary site of coccidioidal infection, lung transplant recipients in endemic areas remain particularly vulnerable. Moreover, direct airway communication to the environment, diminished cough reflex, impaired mucociliary clearance, altered alveolar macrophage function, and ischemic lung injury further enhances the risk of pulmonary infection after lung transplantation. Herein, we review available data on coccidioidomycosis in solid organ transplant recipients and candidates seeking transplantation, and propose strategies for screening, treatment, and prevention of coccidioidal infection in the lung transplant candidate.

Expression of ΔF508 Cystic Fibrosis Transmembrane Regulator (CFTR) Decreases Membrane Sialylation

Chronic colonization and infection of the lung with Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Imundo, et al. determined that CF cells had a higher concentration of an asialoganglioside (asialo-GM1), to which both P. aeruginosa and S. aureus bound preferentially. We sought to determine if the expression of mutant CFTR is associated with altered sialylation. Our study of epithelial cells transfected with normal and mutant ΔF508 CFTR, the defect in the majority of CF patients in the United States, were analyzed by ELISA and FACS analysis of cell membranes labeled with lectins which bind to Neu5Ac. We determined that ΔF508 CFTR is associated with decreased membrane sialic acid residues in the α2, 3 position and increased concentrations of asialo- GM1. Quantitation of sialic acids released from the cellular membranes demonstrated that the presence of the ΔF508 CFTR is associated with markedly decreased membrane sialylation, but similar cytoplasmic sialylation. Thus, ΔF508 defect is correlated with decreased expression of GM1 and with decreased sialylation of all cell surface structures, and this change occurs during post-translational modification of glycoproteins and glycolipids. This may be one factor involved in the chronic bacterial colonization seen in these patients.

A comparison of CF and non-CF school-age children undergoing lung transplantation

Cystic fibrosis (CF) is a genetic disorder resulting in a chloride channel (CFTR) defect characterized by multi‐organ damage. The primary cause of morbidity and mortality is end‐stage obstructive lung disease. Lung transplantation is a treatment option, but is complicated by the risks of acute rejection, Bronchiolitis Obliterans syndrome (BOS) (graft dysfunction), and serious infection. This study sought to assess survival free from three major complications, namely BOS, acute rejection, and serious infection and also to compare overall survival among school‐age CF transplantation recipients to non‐CF recipients. We limited consideration to school‐age children because they comprise a unique cohort in terms of linear and graft growth, immunity, pharmacokinetics and infection exposure as compared with infants, adolescents and adults. The OPTN national database was searched for period between January 1997 and August 2006 for children between 6 and 10 years of age undergoing lung transplantation. Children with CF were compared with non‐CF recipients with regard to occurrence of BOS, infection‐related hospitalizations, and acute rejections. Kaplan–Meier analyses were used for statistical comparisons of the two cohorts. There were 50 CF patients and 37 non‐CF patients available for analysis from the OPTN database. Up to 5 years post‐transplant, there were no statistically significant differences between CF and non‐CF patients in overall survival, and survival free from BOS, acute rejections, or serious infections defined as those requiring hospitalization. Despite having an underlying systemic disease based on defective CFTR, CF school‐age children receiving a lung transplant do not demonstrate more major complications or lower survival than non‐CF children.

Infant anaphylaxis: the importance of early recognition.

Anaphylaxis is an acute severe reaction involving multiple systems that results from a rapid release of inflammatory mediators. Patients with asthma and prior allergic reactions are at risk for anaphylaxis. Infants can present a special challenge, as the hallmark symptoms and signs of anaphylaxis may be mistaken as normal findings. These include drooling, vomiting or diarrhea, scratching, and drowsiness. The clinical manifestations of anaphylaxis are broad, as a result of it being a systemic response to an external agent. Among infants and children, there are often respiratory and cutaneous findings. There also can be subtle signs and symptoms, which can often be missed or the findings misinterpreted as normal for developmental age. The incidence of anaphylaxis has increased globally among children presenting with allergic reactions. Early recognition of the signs and symptoms is crucial to effective diagnosis and treatment. This is particularly true among infants 13 months of age or younger who are nonverbal and may have subtle signs and symptoms of a life-threatening reaction to allergens. The purpose of this article is to highlight the differential clinical presentations of young children with anaphylaxis.

Childhood asthma and anthropogenic CO 2 emissions

Trends in the incidence of childhood asthma worldwide have paralleled the sharp increase in carbon dioxide (CO2) emissions, over at least the last two decades. The prevalence of asthma in the United States has quadrupled over the last 20 years in part due to climate-related factors. In a report released by Harvard Medical School and the Center for Health and the Global Environment, it was noted that there was an increase in asthma incidence of 160% from 1980–1994 among preschool children. This observation was linked to the global rise in CO2 emissions, which in turn affects respiratory exposure to a variety of atmospheric pollens, mold, and fungi.1,2 While asthma is associated with genetic predisposition, the changing environment and air pollution are major contributory factors in the pathogenesis of the disease, and may help explain the rapid change in the incidence of asthma over the last few decades.3 Even though the actual amount of CO2 in the atmosphere is minute, greenhouse gases are very effective in forming a blanket that prevents heat from escaping the earth’s atmosphere.4 Dr Charles Keeling’s research laboratory at Mauna Loa on the Big Island of Hawaii records the amount of CO2 in the atmosphere, adjusted annually for seasonal variations. Analysis of ancient air bubbles trapped by glaciers reveals that the amount of CO2 consistently varied between 200 to 300 parts per million (ppm) for over 80,000 years.4 Since 1960, for the first time in the known history of the earth, CO2 emissions exceeded 300 ppm. In 1980, the levels approached 350 ppm, and have been increasing relatively rapidly ever since, according to the Keeling curve. In turn, global temperatures fluctuate in a pattern that is closely associated with the amount of CO2 in the atmosphere.4

Pediatric anaphylaxis and hyper IgE syndrome

Patients with autosomal-dominant (AD) hyper immunoglobulin E (IgE) syndrome (HIES) or Job syndrome develop frequent dermatologic and pulmonary infections. As patients have an extreme elevation of IgE levels, this database analysis study sought to study the association between AD HIES, Job syndrome, and anaphylaxis. HIES is a heterogeneous group of immune disorders characterized by extremely elevated levels of serum IgE. Although the molecular defects and clinical phenotypes found in association with Job syndrome are well characterized, the association with severe allergic reactions and anaphylaxis is a subject of ongoing investigation.

Neonatal, atopic and infectious disease outcomes among children born to mothers with latent tuberculosis infection

Exposure to microbes may result in maternal immune responses that can affect fetal immune development. Several lines of evidence have shown that mycobacterial antigens can change the onset of atopic disease. We hypothesized that infants born to mothers with a positive tuberculosis (TB) test and a negative chest radiograph, may exhibit differential development of atopic disease during early childhood. The study was designed as a case control study. Birth records for infants born to untreated mothers with a positive TB skin test (TST), as defined by ≥10 mm induration were reviewed (n = 145 cases) and compared to a randomly selected unmatched control cohort of 46 women with a negative TST who delivered during the same time period at Scripps Hospital in San Diego, CA, USA. Childhood outcome parameters reviewed were: (1) the onset of physician diagnosed asthma; (2) lower respiratory tract infection (LRTI) with wheezing, latent tuberculosis infection/wheezing diagnosed on physical examination; (3) nonsurgical hospitalization; (4) atopic disease (eye/skin/nasal-sinus disease); (5) infections: ear, LRTI, sinus. LRTI was defined as an infection of the lower airways, eg, pneumonia. Outcomes at the end of years 1, 2, and 3–5 years combined were analyzed. Fisher exact test, Chi-square analysis or Poisson regression analysis were used as appropriate and a P-value of <0.05 was defined as significant. The cases and controls had similar birth weights, gestational ages, maternal ages: 3.34 versus 3.35 kg; 38.3 versus 39.2 weeks, 27.4 versus 26 years (P = non-significant). The childhood outcome parameters of the new onset of asthma was significantly higher than controls by age 2 years, but not at other ages studied, based on available clinic follow up data (P = 0.02). There was a difference in the risk for lung infection at age 2 and 3–5 years (P < 0.0001). There were no differences in the other outcome parameters studied (P = ns). There were no cases of infants with a positive TST, maternal Bacille Calmette-Guerin vaccination or active maternal TB, based on our study findings. There was a higher occurrence of asthma and lung infections at age 2 years among controls (P = 0.02). Our study defines for the first time a possible influence of maternal latent TB infection on fetal and childhood illness.

Egg introduction: differential allergic responses

The use of egg protein preparations in clinical trials to reduce the incidence of egg allergy among infants includes a number of preparations of egg. These include whole egg, egg white protein, and egg yolk preparations. The study of the differential immune responses to these allergenic proteins in comparison is suggested as a future research area of investigation.

Allergic Rhinitis and Childhood Sleep Disordered Breathing

tions for cases with high risk of food allergy after solid organ transplantation involve dietary manipulations — elimination diet and replacement of tacrolimus by cyclosporine5. In this particular case we suggested cyclosporine therapy and a rigorous elimination diet with avoidance of all poultry meat and Leguminosae. The patient had no complications and has been asymptomatic during one year of follow-up. We describe a rare case of an adult with allergic rhinitis who had serious allergic reactions to various beans and poultry (chicken and turkey). The complexity was increased due to the need for immune suppression for liver transplantation.

Infection and Bronchiolitis Obliterans among Native American Lung Transplant Recipients

Background: Alaska Native and Native American populations (AN/NA) are prone to respiratory tract infections, due to genetic predisposition and environmental factors. Since community acquired respiratory tract infections are associated with higher rates of bronchiolitis obliterans syndrome (BOS), it was hypothesized that AN/NA lung transplant recipients may experience a higher rate of BOS. Methods: The UNOS database was searched from 1995-2005 to identify adult AN/NA patients undergoing lung transplantation in the U.S. Among 11,103 patients, 33 AN/NA (13M/20F) patients were identified for further analysis. Among this population rates of: i) initial hospital stay, ii) first year hospitalizations, iii) hospitalization for infection, iv) subsequent BOS in years 1-5, were compared. Statistical analysis was performed using the fisher exact test, and a p value of <0.05 was considered significant. Results: AN/NA recipients did not have a higher incidence of BOS in years 1-5 following lung transplantation. They did have a higher rate of first year complications, reflected by higher hospitalization rates. AN/NA patients had a higher rate of first year hospitalizations for nonCMV infection (p < 0.03). Conclusions: AN/NA patients despite being at risk for community acquired respiratory infections did not have a higher rate of transplantation BOS in subsequent years.