World J Gastroenterol 2006 May 28; 12(20): 3155-61 (Read article online)

Roberts KE, Duffy AJ, Bell RL

The immense success of laparoscopic surgery as an effective treatment of gastroesophageal reflux disease (GERD) and achalasia has established minimal invasive surgery as the gold standard for these two conditions with lower morbidity and mortality, shorter hospital stay, faster convalescence, and less postoperative pain. One controversy in the treatment of GERD evolves around laparoscopic antireflux surgery (LARS) as the preferred treatment for Barrett's esophagus and the procedure's potential to reduce the risk of adenocarcinoma of the esophagus. GERD has also been associated with respiratory symptoms, asthma and laryngeal injury, and a second controversy prompts discussions about whether total or partial fundoplication is the more appropriate treatment for GERD. A new and promising alternative in the treatment of GERD is endoluminal therapy. Three types of this new treatment option will be discussed: radiofrequency energy delivered to the lower esophageal sphincter, the creation of a mechanical barrier at the gastroesophageal junction, and the direct endoscopic tightening of the lower esophageal sphincter. Laparoscopic surgery is discussed not only as a very effective treatment for GERD but also as permanent cure for achalasia. This review analyzes the three most important treatment options for achalasia: medications, pneumatic dilatation, and surgical therapy. Medications as the only true non-invasive option in the treatment of achalasia are not as effective as LARS because of their short half-life and variable absorption due to the poor esophageal emptying. The second treatment option, pneumatic dilatation, involves the stretching of the lower esophagus and is still considered the most effective non-surgical treatment for achalasia. Finally, surgical therapy for achalasia and the two major controversies concerning this laparoscopic treatment are discussed. The first involves the extent to which the myotomy is extended onto the stomach, and the second concerns the necessity and type of antireflux procedure to prevent GERD after myotomy. LARS and laparoscopic Heller myotomy are the agreed upon as the gold standards for surgical treatment of GERD and achalasia, respectively. In the hands of an experienced laparoscopic surgeon both are safe and effective treatments for patients with excellent subjective and objective long-term results with at least 90% patient satisfaction.

Inhal Toxicol 2006 Jul; 18(8): 523-39 (Read article online)

Reed MD, Campen MJ, Gigliotti AP, Harrod KS, McDonald JD, Seagrave JC, Mauderly JL, Seilkop SK

Hardwood smoke is a contributor to both ambient and indoor air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center, a series of health assays was conducted on rodents exposed to environmentally relevant levels of hardwood smoke. This article summarizes the study design and exposures, and reports findings on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential. Hardwood smoke was generated from an uncertified wood stove, burning wood of mixed oak species. Animals were exposed to clean air (control) or dilutions of whole emissions based on particulate (30, 100, 300, and 1000 mum g/m(3)). F344 rats, SHR rats, strain A/J mice, and C57BL/6 mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Effects of exposure on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential were mild. Exposure-related effects included increases in platelets and decreases in blood urea nitrogen and serum alanine aminotransferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Pulmonary histopathology revealed very little accumulation of hardwood smoke particulate matter. Parallel studies demonstrated mild exposure effects on bronchoalveolar lavage parameters and in a mouse model of asthma. In summary, the results reported here show few and only modest health hazards from short-term to subchronic exposures to realistic concentrations of hardwood smoke.

Eur J Pediatr 2006 May 23; (Read article online)

Xirasagar S, Lin HC, Liu TC

BACKGROUND: Population-based data from Taiwan are used to examine seasonality in pediatric asthma admissions (proxy for asthma exacerbations) and associations with air pollutants and climatic factors. Monthly admission rates per 100,000 population, classified into three age groups, 0~2, 2~5, and 6~14 years (calculated from a total of 27,275 hospitalizations during 1998-2001) were subjected to autoregressive integrated moving average (ARIMA) modeling to examine seasonality. Spearman rank correlations were used to examine associations with criterion air pollutants (PM(10), SO(2), CO, O(3), NO(2)) and meteorological factors (ambient temperature, relative humidity, atmospheric pressure, rainfall, and sunshine hours). RESULTS: Both seasonality and associations with air pollutants and climate factors vary by age group. Among under-twos, the rates are lowest in January-February and highest in November, with a trough in June-July. Among preschoolers, the rates are lowest in June-July and highest in November, with two upsurges in August and March. Among school-goers, admission rates are lowest during June-August, with upsurges in March and September. The number of weather and pollutant predictors increases with age. Among under-twos, only two factors, PM(10) and rainfall, significantly predict admissions. For preschoolers, five factors (PM(10), CO, O(3), temperature, and pressure), and for school-goers, all air pollutants except NO(2,) and all climatic factors except rainfall are significant. CONCLUSION: Seasonality in pediatric asthma admissions vary by age in a subtropical island setting.

Inhal Toxicol 2006 Jul; 18(8): 569-73 (Read article online)

Alipour S, Deschamps F, Lesage FX

The aim of this study was to examine the effects of environmental tobacco smoke (ETS) on pulmonary function and respiratory symptoms. During periodic medical examination, 392 French nonsmokers responded to an interviewer-administered questionnaire. Then spirometry was performed to assess pulmonary function. All of the subjects were carefully examined by two occupational physicians. ETS exposure at the workplace was more common than this exposure at home (20% vs. 5%). ETS exposure was significantly associated with forced vital capacity (FVC; -3.16%; 95% CI: -5.67 to -0.64) and forced expiratory volume in 1s (FEV1; -2.90%; 95% CI: -5.59 to -0.23). Abnormal FVC results were significantly increased in exposed subgroup [odds ratio = 2.71 (95% CI: 1.09 to 6.75)]. We did not find any significant dose-response relationship between ETS exposure and lung function results. The effects of ETS exposure on respiratory symptoms and diseases (asthma, wheezing, chronic bronchitis, and dyspnea) were not significant. Thus, this study showed that there was a significant inverse association between exposure to ETS and pulmonary function. Even pulmonary function results inferior to the lower limit of normal may be possible. A stricter legislation against ETS is proposed.

Inhal Toxicol 2006 Jul; 18(8): 549-54 (Read article online)

Tsai SS, Cheng MH, Chiu HF, Wu TN, Yang CY

This study was undertaken to determine whether there is an association between air pollutants levels and hospital admissions for asthma in Kaohsiung, Taiwan. Hospital admissions for asthma and ambient air pollution data for Kaohsiung were obtained for the period from 1996 through 2003. The relative risk of hospital admission was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days (>/= 25 degrees C) statistically significant positive associations were found in all pollutants except sulfur dioxide (SO(2)). On cool days (

Phytomedicine 2006 Jun; 13(6): 452-6 (Read article online)

Wube AA, Bucar F, Asres K, Gibbons S, Adams M, Streit B, Bodensieck A, Bauer R

Inhibition of leukotriene formation is one of the approaches to the treatment of asthma and other inflammatory diseases. We have investigated knipholone, isolated from the roots of Kniphofia foliosa, Hochst (Asphodelaceae), for inhibition of leukotriene biosynthesis in an ex vivo bioassay using activated human neutrophile granulocytes. Moreover, activities on 12-lipoxygenase from human platelets and cycloxygenase (COX)-1 and -2 from sheep cotyledons and seminal vesicles, respectively, have been evaluated. Knipholone was found to be a selective inhibitor of leukotriene metabolism in a human blood assay with an IC(50) value of 4.2muM. However, at a concentration of 10mug/ml, the compound showed weak inhibition of 12(S)-HETE production in human platelets and at a concentration of 50muM it produced no inhibition of COX-1 and -2. In our attempt to explain the mechanism of inhibition, we examined the antioxidant activity of knipholone using various in vitro assay systems including free radical scavenging, non-enzymatic lipid peroxidation, and metal chelation. Knipholone was found to be a weak dose-independent free radical scavenger and lipid peroxidation inhibitor, but not a metal chelator. Therefore, the leukotriene biosynthesis inhibitory effect of knipholone was evident by its ability either to inhibit the 5-lipoxygenase activating protein (FLAP) or as a competitive (non-redox) inhibitor of the enzyme. Cytotoxicity results also provided evidence that knipholone exhibits less toxicity for a mammalian host cell.

J Pediatr Psychol 2006 May 22; (Read article online)

McQuaid EL, Mitchell DK, Walders N, Nassau JH, Kopel SJ, Klein RB, Wamboldt MZ, Fritz GK

Objective To determine whether family response to asthma symptoms mediates the relationship between child symptom perception and morbidity. Methods A total of 122 children with asthma, aged between 7 and 17 years (47% females; 25% ethnic minorities), were recruited from three sites. Participants completed a family asthma management interview and 5-6 weeks of symptom perception assessment. Results Family response to symptoms mediated the relationship between child underestimation of symptoms and asthma morbidity and partially mediated the relationship between accurate symptom perception and morbidity. In contrast, although child overestimation of symptoms and family response to symptoms were independently related to asthma morbidity, a mediational model was not supported. Conclusions Our study found support for the role of family response to symptoms in mediating the relationship between child symptom perception and morbidity, particularly with regard to underestimation of symptoms, underscoring the need for behavioral tools to accurately recognize and optimally respond to exacerbations.

Immunobiology 2006; 211(5): 351-7 (Read article online)

Yoon JS, Kim HH, Han JW, Lee Y, Lee JS

Endothelial cells (ECs) do more than just play a role in distinguishing blood and tissues. These cells are also influenced by various chemical mediators present in the blood and tissues. In addition, they produce diverse cytokines, chemokines, adhesion molecules, and growth factors. Therefore, ECs are actively involved in the inflammatory and immune response. We investigated the effects of intravenous immunoglobulin (IVIG) and methylprednisolone (MP) on activated human ECs, by examining the individual and combined effects of the drugs. Human umbilical vein ECs (HUVECs) obtained from the umbilical cords of healthy newborns were cultured. After the HUVECs were treated with interleukin (IL)-1beta, the effects of IVIG and/or MP on the activated HUVECs were assessed by cell proliferation, mRNA expression, and the production of vascular cell adhesion molecule (VCAM)-1, IL-1beta, and vascular EC growth factor (VEGF). IVIG and MP inhibited HUVEC proliferation. IVIG and MP significantly down regulated mRNA expression and the production of VCAM-1, IL-1beta, and VEGF. The combination of IVIG and MP generally showed a greater suppressive effect on mRNA expression and on the production of VCAM-1, IL-1beta, and VEGF. Our results suggest that some of the corticosteroid-sparing effects of IVIG observed in patients with severe asthma could be related to a decreased ability of ECs to proliferate, and to a down regulation of the expression of molecules involved in the onset and progression of airway inflammation.

J Leukoc Biol 2006 May 17; (Read article online)

Rose-John S, Scheller J, Elson G, Jones SA

Cytokine receptors, which exist in membrane-bound and soluble forms, bind their ligands with comparable affinity. Although most soluble receptors are antagonists and compete with their membrane-associated counterparts for the ligands, certain soluble receptors are agonists. In these cases, complexes of ligand and soluble receptor bind on target cells to second receptor subunits and initiate intracellular signaling. The soluble receptors of the interleukin (IL)-6 family of cytokines (sIL-6R, sIL-11R, soluble ciliary neurotrophic factor receptor) are agonists capable of transmitting signals through interaction with the universal signal-transducing receptor for all IL-6 family cytokines, gp130. In vivo, the IL-6/sIL-6R complex stimulates several types of cells, which are unresponsive to IL-6 alone, as they do not express the membrane IL-6R. We have named this process trans-signaling. The generation of soluble cytokine receptors occurs via two distinct mechanisms--limited proteolysis and translation--from differentially spliced mRNA. We have demonstrated that a soluble form of the IL-6 family signaling receptor subunit gp130, which is generated by differential splicing, is the natural inhibitor of IL-6 trans-signaling responses. We have shown that in many chronic inflammatory diseases, including chronic inflammatory bowel disease, peritonitis, rheumatoid arthritis, asthma, as well as colon cancer, IL-6 trans-signaling is critically involved in the maintenance of a disease state, by promoting transition from acute to chronic inflammation. Moreover, in all these models, the course of the disease can be disrupted by specifically interfering with IL-6 trans-signaling using the soluble gp130 protein. The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed.

J Natl Med Assoc 2006 Feb; 98(2): 239-47 (Read article online)

Pearlman DN, Zierler S, Meersman S, Kim HK, Viner-Brown SI, Caron C

OBJECTIVE: This study investigates whether racial/ethnic disparities in childhood asthma prevalence can be explained by differences in family and neighborhood socioeconomic position (SEP). METHODS: Data were from the 2001 Rhode Island Health Interview Survey (RI HIS), a statewide representative sample of 2,600 Rhode Island households, and the 2000 U.S. Census. A series of weighted multivariate models were fitted using generalized estimating equations (GEE) for the logistic case to analyze the independent and joint effects of race/ethnicity and SEP on doctor-diagnosed asthma among 1,769 white, black and Hispanic children <18 years old. RESULTS: Compared with white children, black children were at increased odds for asthma and this effect persisted when measures of family and neighborhood SEP were included in multivariate models (AOR: 2.49; 95% Cl: 1.30-4.77). Black children living in poverty neighborhoods had substantially higher odds of asthma than Hispanic and white children in poverty areas and children in moderate- and high-income neighborhoods (AOR: 3.20: 95% Cl: 1.62-6.29). CONCLUSION: The high prevalence of asthma among black children in poor neighborhoods is consistent with previous research on higher-than-average prevalence of childhood asthma in poor urban minority communities. Changing neighborhood social structures that contribute to racial disparities in asthma prevalence remains a challenge.

Curr Med Res Opin 2006 May; 22(5): 809-821 (Read article online)

Lundborg M, Wille S, Bjermer L, Tilling B, Lundgren M, Telg G, Ekström T, Selroos O

OBJECTIVE: To evaluate efficacy and cost-effectiveness of budesonide/formoterol (Symbicort) maintenance (one dose once or twice daily) plus additional doses as needed (Symbicort Maintenance And Reliever Therapy, SMART) compared with a higher fixed dose of budesonide/formoterol with formoterol as needed in patients with persistent asthma.Study design and methods: 6-month, open, randomised study of 465 patients either not well controlled on an inhaled corticosteroid (ICS), or well controlled on a combination of ICS and a long-acting beta(2)-agonist (LABA). Treatments: budesonide/formoterol 160/4.5mug, one inhalation, once or twice daily maintenance plus additional doses as-needed (1 x SMART or 2 x SMART), or budesonide/formoterol 160/4.5mug two inhalations twice daily plus formoterol 4.5mug as needed (2 x 2 FIX + F). Children 6-11 years old used an 80/4.5mug dose strength. Primary variables of efficacy were the changes in the Asthma Control Questionnaire (ACQ(5)) and morning peak expiratory flow (PEF).RESULTS: Mean age of patients 40 years (range 6-82 years); 53% female. No differences between the groups were found in ACQ(5) scores or asthma exacerbation rates. Morning PEF was higher in the 2 x 2 FIX + F group vs. the 1 x SMART and 2 x SMART groups (differences 13 L/min and 9 L/min, respectively; p < 0.002). The 1 x SMART group showed a significant decrease in asthma controlled days compared with the two other groups. No difference was seen between the 2 x SMART group and the 2 x 2 FIX + F group. Treatment costs were significantly lower in the SMART groups compared with the 2 x 2 FIX + F group.CONCLUSION: Compared with the 2 x 2 FIX + F treatment the use of budesonide/formoterol was 30-40% lower in the SMART groups while maintaining equal ACQ(5) scores. Daily asthma control improved equally with 2 x SMART compared to 2 x 2 FIX + F with a reduction in asthma medication cost. The one dose once daily maintenance treatment (1 x SMART) resulted in a low level of treatment failure (exacerbations) but led to more days with symptoms. Therefore, a daily dose of two inhalations seems to be the lowest appropriate dose in patients with moderate persistent asthma.

J Natl Med Assoc 2006 Feb; 98(2): 138-42 (Read article online)

Hasan RA, Zureikat GY, Nolan BM, LaChance JL, Campe JL, Amin R

BACKGROUND: This study was performed to determine the relationship between overweight [body mass index (BMI) > or = 85th percentile] and asthma as determined by spirometry. METHOD: Spirometry was performed according to the American Thoracic Society guidelines, and BMI was calculated. Asthma was defined as a forced expiratory volume in 1 second (FEV1) <80% predicted and FEV1/forced vital capacity (FVC) >5% lower than predicted for age and sex. RESULTS: One-hundred-nine children (age 14.7 +/- 1.6 years) were enrolled. Eighty children (73%) were African-American, and 29 children (27%) were white. Fifty-eight (53%) children were overweight. Twelve (11%) children, of whom nine (75%) were overweight, met the criteria for asthma. Baseline FEV1 percent predicted (87 +/- 6% vs. 83 +/- 7%, p=0.03), FEV1/FVC (93 +/- 6 vs. 87 +/- 8, p<0.001), and FEV1 percent predicted following albuterol administration (94 +/- 7 vs. 89 +/- 7%, p=0.03) were all lower in overweight children. Children with asthma were almost 1.5 times more likely to be overweight compared with children without asthma (relative risk: 1.49, 95% confidence interval: 1.015-2.17). CONCLUSIONS: Inner-city children are more likely to be overweight compared to the general population. Asthma is a risk factor for overweight in these children.

Eur Respir J 2006 May 17; (Read article online)

Douwes J, McLean D, Slater T, Travier N, Cheng S, Pearce N

We have previously shown an increased risk of asthma symptoms in 772 pine sawmill workers. The current study assessed the association between dust exposure, lung function and atopy.Subjects with (n=59) and without asthma symptoms (n=167) were randomly selected from the previous survey. Lung function and atopy were determined using spirometry and skin prick tests respectively. Inhalable dust was measured on the same day.The geometric mean dust concentration was 0.52 mg.m(-3) (GSD, 2.66). Exposure to "dry" dust but not green dust was associated with asthma symptoms (OR, 2.1, CL 1.0-4.4). "Green" dust was associated with atopic sensitisation, particularly against outdoor allergens (OR 2.23, CL 1.02, 6.46); no association was found for "dry" dust. FVC, FEV1, and PEF were significantly lower in high "green" dust (-350 ml; -260 ml; and -860 ml.s(-1), respectively) and high "dry" dust exposed workers (-230 ml; -190 ml; and -850 ml.s(-1), respectively). These associations were observed both in subjects with and without asthma symptoms. No associations with cross-shift changes in lung function were found.Exposure to "green" pine sawdust may be a risk factor for atopy. Both "green" and "dry" dust were associated with obstructive as well as restrictive pulmonary effects.

J Pediatr Gastroenterol Nutr 2006 May; 42(5): 531-534 (Read article online)

Iacono G, Di Prima L, D'Amico D, Scalici C, Geraci G, Carroccio A

INTRODUCTION:: Red umbilicus is considered to be an infectious disease typical of neonates. In our experience, umbilical erythema could be due to cow's milk protein intolerance (CMPI). AIMS:: To evaluate the frequency and clinical significance of umbilical erythema in a series of consecutive children referred for suspected CMPI. PATIENTS AND METHODS:: Seven hundred ninety-six consecutive patients (median age, 18 months) referred for suspected CMPI diagnosis were studied. CMPI diagnosis was based on the disappearance of symptoms on elimination diet and their subsequent reappearance on double-blind placebo-controlled cow's milk challenge. RESULTS:: CMPI was diagnosed in 384 patients: 120 with respiratory, 75 dermatologic and 198 gastroenterological symptoms. Although some patients showed more than 1 type of symptom, whether gastroenterological, dermatologic or respiratory, they were classified in 1 category only according to the main reason for referral to the outpatients clinic. Umbilical erythema was observed in 36 patients (median age, 10 months): 16 (8%) with gastroenterological symptoms, 9 (7.5%) with recurrent asthma and 11 (15%) with atopic dermatitis. None of the symptomatic controls without CMPI had umbilical erythema. On elimination diet, the erythema disappeared within the second week. On CMPI challenge, it reappeared within 24 hours. CONCLUSIONS:: Umbilical erythema can be a sign of food intolerance and can be a useful diagnostic tool for CMPI.

Am J Epidemiol 2006 May 17; (Read article online)

Levan TD, Koh WP, Lee HP, Koh D, Yu MC, London SJ

Occupational factors contribute to a significant fraction of respiratory disease and symptoms. The authors evaluated the role of occupational exposures in asthma, chronic bronchitis, and respiratory symptoms in the Singapore Chinese Health Study, a population-based cohort of adults aged 45-74 years at enrollment in 1993-1998. Information on occupations and occupational exposures was collected at enrollment for 52,325 subjects for whom respiratory outcomes were obtained via follow-up interviews in 1999-2004. Exposure to dusts from cotton, wood, metal, minerals, and/or asbestos was associated with nonchronic cough and/or phlegm (odds ratio (OR) = 1.19, 95% confidence interval (CI): 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI: 1.01, 1.57), and adult-onset asthma (OR = 1.14, 95% CI: 1.00, 1.30). Cotton dust was the major contributor to respiratory symptoms. Vapor exposure from chemical solvents, dyes, cooling oils, paints, wood preservatives, and/or pesticides was associated with nonchronic cough or phlegm (OR = 1.14, 95% CI: 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI: 1.19, 2.01), and adult-onset asthma (OR = 1.34, 95% CI: 1.15, 1.56). Chemical solvents, cooling oils, and pesticides were the major contributors to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness.

J Clin Invest 2006 May 18; (Read article online)

Yu M, Tsai M, Tam SY, Jones C, Zehnder J, Galli SJ

Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5ac and Muc5b, and increased levels of lung collagen. Using mast cell-deficient (Kit(W-sh/W-sh) and/or Kit(W/W-v)) mice engrafted with FcRgamma(+/+) or FcRgamma(-/-) mast cells, we found that mast cells were required for the full development of each of these features of the model. However, some features also were expressed, although usually at less than wild-type levels, in mice whose mast cells lacked FcRgamma and therefore could not be activated by either antigen- and IgE-dependent aggregation of FcepsilonRI or the binding of antigen-IgG1 immune complexes to FcgammaRIII. These findings demonstrate that mast cells can contribute to the development of multiple features of chronic asthma in mice and identify both FcRgamma-dependent and FcRgamma-independent pathways of mast cell activation as important for the expression of key features of this asthma model.

Am J Respir Cell Mol Biol 2006 May 18; (Read article online)

Prado CM, Leick-Maldonado EA, Yano L, Leme AS, Capelozzi VL, Martins MA, Tiberio IF

Rationale: The precise role of each nitric oxide synthase isoforms (NOS) in the pathobiology of asthma is not well established. Objective: To investigate the contribution of constitutive (cNOS) and inducible (iNOS) isoforms to lung mechanics, inflammatory and remodeling responses in an experimental model of chronic allergic pulmonary inflammation. Methods: Guinea pigs were submitted to seven ovalbumin exposures with increasing doses (1~5 mg/mL) for four weeks. The animals received either chronic L-NAME (N-nitro-L-arginine methyl ester, in drinking water) or 1400W (iNOS specific inhibitor, i.p.) treatments. Seventy-two hours after the seventh inhalation of ovalbumin solution, animals were anesthetized, mechanically ventilated, exhaled nitric oxide was collected and lung mechanical responses were evaluated before and after antigen challenge. Results: Both L-NAME and 1400W treatments increased baseline resistance and decreased elastance of the respiratory system in non-sensitized animals. After challenge, L-NAME increased resistance of the respiratory system and collagen deposition on airways and decreased peribronchial edema and mononuclear cell recruitment. Administration of 1400W reduced resistance of the respiratory system response, eosinophilic and mononuclear cell recruitment, and collagen and elastic fibers content in airways. L-NAME treatment reduced both iNOS and neuronal NOS positive eosinophils and 1400W diminished only the number of eosinophils expressing iNOS. Conclusions: In this experimental model, inhibition of NOS-derived NO by L-NAME treatment potentates bronchoconstriction and increases the collagen deposition. However, blockage of only iNOS attenuates bronchoconstriction, and inflammatory and remodeling processes.

Med Care 2006 Jun; 44(6): 560-567 (Read article online)

Schrag D, Xu F, Hanger M, Elkin E, Bickell NA, Bach PB

BACKGROUND:: Fragmentation across sites of care may impede efficient healthcare delivery. OBJECTIVES:: The objectives of this study were to evaluate fragmentation of hospital care for chronically ill New York City (NYC) residents and its association with enrollment in the New York State (NYS) Medicaid program. RESEARCH DESIGN:: We conducted a cross-sectional study using the NYS Department of Health's Statewide Planning and Research Cooperative System discharge database. We identified 53,031 NYC residents admitted 3 or more times to acute care hospitals between 2000 and 2002 with the same principal diagnosis of a specific chronic illness (diabetes, sickle cell anemia, psychosis, substance abuse, cancer, gastrointestinal disease, chronic obstructive pulmonary disease/asthma, coronary artery disease, or congestive heart failure). We also evaluated a larger cohort of 225,421 patients with >/=3 admissions for a specific chronic illness coded as either the principal or a secondary diagnosis. A generalized logit model was used to examine the relationship between fragmentation and each patient's primary insurance adjusted for diagnosis and demographic characteristics. MEASURES:: Fragmentation was characterized as high, moderate, or low based on the number of distinct hospitals a patient visited relative to the patient's total number of hospitalizations over the 3-year interval. RESULTS:: Among frequently hospitalized NYC residents with select chronic conditions, 17.1% experienced highly fragmented care. This rate was 9.9% for patients with commercial insurance, 24.4% for those with Medicaid, and 9.7% for those with Medicare. The unadjusted odds ratio describing high fragmentation of Medicaid enrollees compared with commercially insured patients was 3.82 (95% confidence interval [CI], 3.50-4.18) and, although attenuated, remained significant after adjustment for demographic characteristics (odds ratio, 1.33; 95% CI, 1.20-1.47). The strongest predictor of fragmentation was a diagnosis of psychosis (OR, 2.81; 95% CI, 2.43-3.25) or substance abuse (OR, 7.58; 95% CI, 6.55-8.77). CONCLUSIONS:: In NYC, Medicaid enrollment is associated with greater fragmentation of hospital care, but this is largely attributable to the preponderance of Medicaid enrollees with diagnoses of psychosis and substance abuse. Strategies to improve the efficiency of healthcare delivery should focus on patients with mental illness who are frequently admitted to general hospitals.

Respir Res 2006 May 18; 7(1): 78 (Read article online)

Singhera GK, Chan TS, Cheng JY, Vitalis TZ, Hamann KJ, Dorscheid DR

ABSTRACT: BACKGROUND: Effects of respiratory viral infection on airway epithelium include airway hyper responsiveness and inflammation. Both features may contribute to the development of asthma. Excessive damage and loss of epithelial cells are characteristic in asthma and may result from viral infection. OBJECTIVE: To investigate apoptosis in Adenoviral infected Guinea pigs and determine the role of death receptor and ligand expression in the airway epithelial response to limit viral infection. METHODS: Animal models included both an Acute and a Chronic Adeno-infection with ovalbumin induced airway inflammation with/without corticosteroid treatment. Isolated airway epithelial cells were cultured to study viral production after infection under similar conditions. Immunohistochemistry, western blots and viral DNA detection were used to assess apoptosis, death receptor and TRAIL expression and viral release. RESULTS: In vivo and in vitro Adeno-infection demonstrated different apoptotic and death receptors (DR) 4 and 5 expression in response to corticosteroid exposure. In the Acute Adeno-infection model, apoptosis and DR4/5 expression was coordinated and were time-dependent. However, in vitro Acute viral infection in the presence of corticosteroids demonstrated delayed apoptosis and prolonged viral particle production. This reduction in apoptosis in Adeno-infected epithelial cells by corticosteroids exposure induced a prolonged virus production via both DR4 and TRAIL protein suppression. In the Chronic model where animals were ovalbumin-sensitized/challenged and were treated with corticosteroids, apoptosis was reduced relative to adenovirus-infected or corticosteroid alone. CONCLUSION: Our data suggests that apoptosis of infected cells limits viral production and may be mediated by DR4/5 and TRAIL expression. In the Acute model of Adeno-infection, corticosteroid exposure may prolong viral particle production by altering this apoptotic response of the infected cells. This results from decreased DR4 and TRAIL expression. In the Chronic model treated with corticosteroids, a similar decreased apoptosis was observed. This data suggests that DR and TRAIL modulation by corticosteroids may be important in viral infection of airway epithelium. The prolonged virus release in the setting of corticosteroids may result from reduced apoptosis and suppressed DR4/TRAIL expression by the infected cells.

J Natl Med Assoc 2006 Feb; 98(2): 249-60 (Read article online)

Williams SG, Brown CM, Falter KH, Alverson CJ, Gotway-Crawford C, Homa D, Jones DS, Adams EK, Redd SC

OBJECTIVE: To evaluate the impact of a multifaceted environmental and educational intervention on the indoor environment and health in 5-12-year-old children with asthma living in urban environments. DESIGN: Changes in indoor allergen levels and asthma severity measurements were compared between children who were randomized to intervention and delayed intervention groups in a 14-month prospective field trial. Intervention group households received dust mite covers, a professional house cleaning, and had roach bait and trays placed in their houses. RESULTS: Of 981 eligible children, 410 (42%) were enrolled; 161 (40%) completed baseline activities and were randomized: 84 to intervention and 77 to delayed intervention groups. At the study's end, dust mite levels were 163% higher than at baseline for the delayed intervention group. Overall asthma severity scores did not change. However, the median functional severity score (FSS) component of the severity score improved more in the intervention group (33% vs. 20%) than in the delayed intervention group. At the study's end, the median FSSs for the intervention group improved 25% compared with the delayed intervention group, (p<0.01). Differences between groups for medication use, emergency department (ED) visits or hospitalization were not significant. CONCLUSIONS: Despite low retention, the intervention resulted in decreased dust mite allergen levels and increased FSSs among the intervention group. The interventions probably contributed to the improvements, especially among the more severely affected children. This study highlights the complexities of designing and assessing the outcomes from a multifaceted asthma intervention.