Efficacy of high-dose intra-dermal hepatitis B virus vaccine in previous vaccination non-responders with chronic liver disease.

BACKGROUND: Hepatitis B virus (HBV) vaccination is essential in chronic liver disease (CLD), because it can help prevent acute-on-chronic disease, which has potentially fatal complications. Unfortunately, this group has a significant proportion of HBV vaccination non-responders. A variety of intra-muscular (IM) vaccination methods have been used in an attempt to remedy this poor-response, but with limited success. AIMS: Herein is reported the safety and efficacy of high-dose intra-dermal (ID) HBV vaccination in CLD individuals who had failed previous IM standard and boost-dosing regimens. METHODS: Forty-eight CLD individuals, known HBcAb negative, who had failed both a three-dose schedule of 40 µg IM vaccination, and boost dosing of either 40 or 80 µg IM, were identified, of which 42 completed the vaccination course. Each received a 40 µg ID total dose (20 µg per arm) during their clinic visits until a response was documented or a maximum of three doses had been administered. HBsAb titer ≥ 10 mIU/ml was regarded as an immunologic response; the intention was to achieve an optimum response of ≥ 100 mIU/ml. RESULTS: Twenty-nine of forty-two (69%) individuals had an immunologic response, with 15 (51%) of the responders having the optimum response. No changes in serologic data occurred. No serious dermatologic reactions were observed. No differences between those who responded and those who did not were observed with regard to the presence of cirrhosis, diabetes mellitus, or chronic kidney disease. CONCLUSIONS: High-dose ID HBV vaccination of previous CLD non-responders to the standard IM regimen with boost dosing is both safe and efficacious, and should be considered for all such groups.

Asthma control test and peak expiratory flow rate: independent pediatric asthma management tools.

BACKGROUND: Management of asthma reflects the complexity of the pathogenesis. According to current National Heart Lung Blood Institute (NHLBI) guidelines, asthma control can be assessed using the validated asthma control test, measures of airway function, and overall assessment of risk and quality of life. We hypothesized that the asthma control test and measures of airway function are independent tools in asthma management. We also studied whether the presence of nasal symptoms is correlated to these measures. METHODS: Serial visits (n = 45) to a pediatric respiratory clinic in an underserved area of San Diego County with a predominantly Hispanic population were reviewed. Patients were included if they were able to perform airway function tests and had more than one provider visit. Patients with other major diseases were excluded. We determined whether uncontrolled asthmatics, defined as an Asthma Control test (ACT) score of 19 or less, had lower % predicted peak expiratory flow Measurements as a group compared to those with higher scores. In addition, the individual ACT and airway function results were analyzed. Patients with and without nasal symptoms at the time of presentation were sub-analyzed to determine differences in ACT and peak flow measurements. RESULTS: Based on n = 45 physician visits, the mean ACT score was 21 +/- 3.3 (range 12-25) and the mean peak expiratory flow rate (PEFR) was 87.4% +/- 11 (range 65-109%). Patients with ACT scores < or = to 19 or lower (< or = 90%) PEFRs were determined not to have more nasal symptoms. The measures of ACT and peak expiratory flow were independent and not correlated. CONCLUSIONS: Our study indicates that ACT and PEFR are distinct parameters used to manage patients in a pediatric outreach asthma clinic.

Pirfenidone: a novel potential therapeutic agent in the management of chronic allograft rejection.

Chronic allograft dysfunction is a leading cause of allograft failure, morbidity, and mortality after solid organ transplantation. The pathogenesis of chronic allograft failure has a final common pathway leading to organ fibrosis. Pirfenidone is an effective and novel antifibrotic agent with anti-inflammatory properties. Clinical use of the agent has been tested in a number of nontransplant recipients and has a favorable safety profile based on available clinical data. Building on these observations and findings, and considering the role of fibrosis in chronic allograft rejection, pirfenidone was initially investigated as adjunct therapy in a rat heterotopic tracheal transplantation model. This led to several studies confirming that pirfenidone may well be worth considering for further investigation. This paper reviews the possibility of using pirfenidone in clinical transplantation management.

The bronchoalveolar lavage fluid of cystic fibrosis lung transplant recipients demonstrates increased interleukin-8 and elastase and decreased IL-10.

Cystic fibrosis (CF) patients continue to have reservoirs of Pseudomonas aeruginosa infection in their sinuses and trachea after transplantation, and studies indicate that nontransplanted CF patients have high bronchoalveolar lavage (BAL) levels of proinflammatory factors, interleukin-8 (IL-8), and elastase and decreased airway lavage levels of IL-10. The aims of our study were to measure the IL-8 and IL-10 levels and elastase activity in the BAL of lung transplant patients, with correlation to microbiologic and pathologic findings, and to identify any differences in the findings between CF and non-CF patients. Fifty serial BAL samples were collected from 38 lung transplant recipients over 8 months. The BAL supernatant fluid was cultured for bacterial, viral, and fungal organisms. Histologic tissue analysis was performed as indicated. The fluid IL-10 and IL-8 levels were measured in duplicate using ELISA techniques. Elastase activity was measured using a colorimetric assay system. The mean IL-8, IL-10, and elastase levels for the group studied were 1894 pg/ml, 394 pg/ml, and 4.2 U/ml, respectively. The CF patients had significantly higher levels of IL-8, with a mean value of 4093 pg/ml (p < 0.02), and lower IL-10, mean 217 pg/ml (n = 9). Elastase activity correlated strongly with IL-8 level (p < 0.04). Pseudomonas growth was associated with higher elastase and IL-8 concentrations (p < 0.02). There was no association between allograft rejection and the markers studied. CF transplanted patients have higher airway lavage concentrations of IL-8 and elastase correlated to the presence of Pseudomonas in the lower airway. They also have lower BAL levels of anti-inflammatory cytokine IL-10.

Activation of eosinophils in the airways of lung transplantation patients.

UNLABELLED: Eosinophils are important inflammatory cells involved in liver and renal allograft rejection. The role of these cells is less well defined in lung allograft rejection. Eosinophils may be activated in lung rejection and release cytotoxic eosinophil cationic protein (ECP). Other states of disease in lung transplant recipients, such as cytomegalovirus (CMV) and bacterial infection, may also be associated with activated eosinophils. We postulated that ECP may be detectable and elevated in the airway lavage samples obtained from lung transplant patients and may contribute to disease pathogenesis. METHODS: Fifty BAL samples were collected from 38 lung transplant patients. Their most recent pulmonary function test results within 1 week of collection were noted. The samples were analyzed for the concentration of ECP, WBC count and differential cell count, and total protein level. The results were analyzed to identify the presence of disease or abnormal lung function associated with a positive ECP test. Student's t test was used and a p value of <0.05 was considered significant. RESULTS: We found that ECP levels were elevated in 36% (n=14) of the patients. Those patients with a positive test result were more likely to have acute rejection, CMV disease, or the presence of a cultured pathogen in BAL compared to patients with a negative test result (p<0.01). CONCLUSIONS: The presence of BAL ECP is associated with disease in lung transplant patients. Since ECP is directly cytotoxic, it may contribute to disease pathogenesis.

Liquid ventilation provides uniform distribution of perfluorocarbon in the setting of respiratory failure.

BACKGROUND: We evaluated the effect of perfluorocarbon liquid ventilation (LV) on gas exchange and pulmonary function in the setting of respiratory failure and the distribution of the ventilating medium during LV when compared to gas ventilation (GV). METHODS: Ten sheep, 17.3 +/- 4.2 kg in weight, underwent oleic acid induction of lung injury followed by either GV (n = 5) or perfluorocarbon LV (n = 5). After 1 hour animals were killed, and chest computed tomographic (CT) imaging was performed. Average CT attenuation number was assessed as an indicator of the distribution of gas or perfluorocarbon in the dependent (posterior) and nondependent (anterior) zones of the lung (air = -1000; soft tissue = 0; perfluorocarbon = +2300 Hounsfield units [H]). RESULTS: Significant increases in PaO2 (LV = 298 +/- 76 mm Hg, GV = 43 +/- 18 mm Hg, p < 0.001), SvO2 (LV = 74% +/- 6%, GV = 32% +/- 18%, p < 0.01), and lung compliance (LV = 1.65 +/- 0.50 ml/cm H2O/kg, GV = 0.58 +/- 0.06 ml/cm H2O/kg, p < 0.01) were observed. Significant decreases in physiologic shunt (LV = 24% +/- 6%, GV = 62% +/- 14%, p < 0.01) were noted. CT attenuation data showed the presence of minimal gas ventilation in the dependent regions during GV although the nondependent regions remained well aerated (CT attention number during GV: ND = -654 +/- 160 H; D = -92 +/- 160 H, p < 0.0001). During LV, there was a fairly homogenous distribution of perfluorocarbon in the lungs (CT attenuation number during LV: D = 1071 +/- 330 Hounsfield units; ND = 1112 +/- 287 Hounsfield units; p = 0.240). Lung biopsy analysis in the LV animals was consistent with a reduction in intraalveolar hemorrhage, intraalveolar edema, and the inflammatory infiltrate. CONCLUSIONS: On the basis of the data, we conclude that in this lung injury model, (1) the distribution of the ventilating medium is uniform during LV when compared to GV, (2) LV improves gas exchange and pulmonary function, and (3) histologic evidence of lung injury is reduced after LV when compared to GV.

Bronchioalveolar carcinoma in a 15-year-old girl.

This report describes a 15-year-old female from Venezuela who has bronchioalveolar carcinoma. She is one of the youngest patients with this particular diagnosis reported in the literature. The postulated age of onset in this case was 13 years, when the first lesion was noted. Bronchioalveolar carcinoma is an extremely rare diagnosis in the pediatric population. The paucity of symptoms in this disease can lead to a delay in diagnosis. Malignancy should be considered in all cases of pediatric pulmonary lesions. Bronchoscopy and transbronchial biopsy in cases of alveolar carcinoma are not particularly useful because of the peripheral location of the lesions.

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.

Chronic pediatric pulmonary disease and primary humoral antibody based immune disease.

Chronic inflammation of the larger airways is a common occurrence in children. A number of factors such as younger age, premature birth, male gender, exposure to environmental smoke or pollution, and crowded housing can increase a child's susceptibility to chronic lung disease. Chronic bronchitis may be caused by an underlying humoral immunodeficiency if the clinical course is recurrent or prolonged. Primary humoral immunodeficiency accounts for approximately 70% of all immunodeficiencies. The differential of chronic bronchitis also includes Cystic Fibrosis, ciliary defects and immune cellular and phagocytic defects. This review will summarize the most common humoral antibody based immune based deficiencies associated with chronic pulmonary disease.

Successful management of recurrent coccygeal hernia with the de-epithelialised rectus abdominis musculocutaneous flap.

OBJECTIVE: Little data exist about the optimal management of the rare coccygeal hernia. A novel method of repair is reported. METHODS: A 46-year-old woman presented with a symptomatic coccygeal hernia after resection of the coccyx for a tumour. She had previously been reconstructed with an on-lay polytetrafluorethylene (PTFE) mesh but subsequently developed a hernia. A de-epithelialised vertical rectus abdominis musculocutaneous flap was elevated and passed through the hernia defect. The de-epithelialised dermis was secured to the levator ani and to the periosteum of the sacrum via access through a posterior approach. The gluteal skin was closed primarily over the inset flap. RESULTS: The de-epithelialised rectus abdominis musculocutaneous flap is a viable option for the treatment of coccygeal hernia. RELEVANCE: The de-epithelialised rectus abdominis flap has several advantages over other techniques including mesh repair and anterior or posterior flap repairs of the coccygeal hernia. The transposed muscle blocks herniation through the pelvic floor and does not create the dead space that is associated with posterior flap repairs such as the bilateral gluteal advancements. It also has the advantages of the posterior approach mesh repair, as the de-epithelialised dermis provides significant strength when secured like mesh to healthy local tissue.

A review of nutritional problems and the cystic fibrosis lung transplant patient.

Lung transplantation is an option for some cystic fibrosis (CF) patients. CF is associated with a variety of non-pulmonary problems, which should be managed before and after transplantation. This commentary discusses some of the nutritional issues affecting CF patients. Theses issues include: the need for nutritional supplements; gastrostomy tube placement; osteoporosis and diabetes.

Immunolocalization of G(alpha)i-3 in foetal lung fibroblasts.

Guanosine triphosphate (GTP)-binding proteins or G proteins are involved in a wide variety of well-recognized signalling activities between cell surface receptors and effectors. The heterotrimeric G proteins have alpha,beta and gamma subunits organized in a trimeric structure. The aim of this study was to localize G(alpha)i-3, an important heterotrimeric G protein, in foetal lung cells. Using a foetal lung fibroblast cell line (RFL-6), the localization of G(alpha)i-3 was determined by immunofluorescence using a specific antibody to G(alpha)i-3, colocalization with a lectin known to bind the Golgi complex and Western blotting of RFL-6 cellular membrane proteins. This study identified G(alpha)i-3 on the Golgi membranes in rat foetal lung cells. Treatment with cycloheximide, to block protein synthesis, diminished the cytosolic distribution of the protein, but intense Golgi staining remained. G(alpha)i-3, therefore, appears to be part of the Golgi complex and not present transiently during protein synthesis. In the nonpolar foetal lung fibroblasts studied, the intracellular concentration of G(alpha)i-3 suggests a role for this protein in the intracellular trafficking and regulation of proteins needed for normal lung development.

Endothelin-1 (ET-1) decreases human bronchial epithelial cell migration and proliferation: implications for airway remodeling in asthma.

The respiratory epithelium is a protective barrier that also functions as an interactive metabolically active component of the lung. The healing and repair of the epithelium involves initial migration of epithelial cells, and subsequent proliferation. The purpose of our study was to assess the effect of inflammatory mediators, in particular endothelin-1 (ET-1), on bronchial epithelial cell proliferation and migration. Under the conditions studied, ET-1 slows proliferation of human bronchial epithelial cells, compared to control (p < 0.01). The presence of ET-1 results in slower migration of epithelial cells compared to control (p < 0.04). Based on these in vitro findings, ET-1 could potentially lead to inhibition of repair of the lung epithelium and enhanced remodeling.

Respiratory syncytial virus augments production of fibroblast growth factor basic in vitro: implications for a possible mechanism of prolonged wheezing after infection.

Respiratory syncytial virus (RSV) has been linked to the development of clinical asthma. Cellular mechanisms of this observation are not yet clearly elucidated. In chronic asthma, production of growth factors and remodeling are associated with prolonged wheezing. It was hypothesized that cells infected with RSV may produce excessive levels of fibroblast growth factor basic (FGFb), and epidermal growth factor (EGF). Airway epithelial cells were incubated with either: (i) virus, (ii) inactivated virus, or (iii) media only. The levels of FGFb and EGF were measured in the cellular supernatant fluid. The study demonstrated that by 24 h after RSV inoculation, or exposure to RSV-killed virus, cells are stimulated to produce significantly more FGFb, compared with non-infected/non-exposed control cells. FGFb is an important factor in remodeling and fibroblast activation in the airway. Using treatment with actinomycin D and cylcohexamide the effect of inhibiting translation or transcription in the infected cells, on FGFb production was demonstrated. There were no alterations in EGF production detectable. Based on the findings, the mechanism of FGFb secretion after RSV inoculation, appears to be regulated at the levels of both transcription and translation. The increased FGFb release potentially could contribute to fibroblast activation and remodeling in the airway, and thus provide another possible mechanism for prolonged wheezing after infection.