Biomedical subjects

Carol J Blaisdell

Publications and source records attributed to Carol J Blaisdell.

12 recordsLinked to original sources

PubMed2006

Risk areas for pediatric acute care: asthma differs from upper and lower respiratory illness.

OBJECTIVE: To determine if emergency department utilization for pediatric respiratory illness varies across small geographic jurisdictions within a large urban city. DESIGN: A retrospective analysis of Maryland Health Services Cost Review Commission Emergency Department discharge data. SETTING/PATIENTS: All non-neonatal, Baltimore City residents <18 years old with valid diagnoses admitted and discharged from emergency departments (ED) in the state of Maryland from April 1, 1997 to December 31, 2000 (n=245,339). MAIN OUTCOME MEASURES: Crude and adjusted ED visit rates for asthma, upper and lower respiratory illnesses (per 1000 population). To evaluate the effect of geography on pediatric ED visit rates, odds of an asthma ED visit, URI, or LRI vs. non-respiratory ED visit were compared across regions of the city. RESULTS: We determined that residential areas with high ED utilization rates for upper and lower respiratory illnesses, as well as non-respiratory illnesses correlate with regions of high ED utilization for asthma, even after adjusting for race, gender and age of the population. The regions with high odds ratios that an ED visit was for asthma were different from those with high ORs for URI and LRI after also controlling for poverty. CONCLUSIONS: This suggests that poverty accounts for high utilization of the ED in urban settings, but suggests that environmental exposures that increase the risk of ED care for asthma differ from those that lead to URI and LRI.

Acute Disease↗

PubMed2006

Acidic pH hyperpolarizes nasal potential difference.

Nasal potential difference (NPD) has served as a non-invasive diagnostic method for cystic fibrosis (CF) a disease of chloride channel expression and function in secretory epithelia. Investigators have also used NPD to demonstrate ion transport abnormalities in newborns with respiratory distress. Standard perfusates for diagnostic NPD studies include the use of amiloride, replacement of chloride with gluconate, cAMP agonists, and nucleotides such as ATP. The pH of these perfusates may also be relevant to NPD studies as we have previously shown that the respiratory epithelia in mammals express CLC-2, which is a pH sensitive chloride channel. We hypothesized that acidic pH might activate chloride secretion in vivo if CLC-2 is present in human respiratory epithelia. Our objective was to determine the effect of acidic pH on NPD measurements and the frequency of expression of CLC-2 in normal subjects. Healthy adults were recruited and CLC-2 protein expression was detected in 20 of 29 primary nasal epithelial cell cultures. Acidic pH stimulated NPD responses in 33% of subjects. These findings suggest that pH sensitive alternative pathways are available for modulation in human respiratory epithelia and that NPD protocols should standardize pH of perfusates.

Acidosis↗

PubMed2006

Looking beyond urban/rural differences: emergency department utilization by asthmatic children.

Asthma causes pediatric morbidity throughout the US with substantial regional variability. Emergency department (ED) utilization data were studied to determine if geographic variability of pediatric asthma cases exists within a state. Records for non-neonatal Maryland children less than 18 years of age seen and discharged from Maryland EDs from April 1997 through March 2001 were analyzed. While Baltimore City had the highest rates of asthma visits, adjusted odds ratios identified the wealthiest suburban county to have a higher risk of an asthma ED visit. Children from rural counties, for the most part, had fewer ED asthma visits than children from urban and suburban counties.

Adolescent↗

PubMed2004

Interferon-gamma regulates ClC-2 chloride channel in lung epithelial cells.

Epithelial Cl(-) channels mediate Cl(-) and fluid secretion in the lung. In cystic fibrosis, aberrant Cl(-) secretion is one of the major causes for lung fluid imbalance. Regulation of Cl(-) channels is therefore an important issue in the lung. IFN-gamma regulates Na(+) and Cl(-) channels and fluid transport in the lung, but the mechanisms involved in these regulations are not clear. In expression studies, we found that IFN-gamma increased ClC-2 transcripts in Calu-3 cells. Studies of the promoter identified a minimal promoter which interacts with transcription factors Sp1 and Sp3. However, reporter gene assays showed that IFN-gamma did not activate the promoter. Instead, IFN-gamma significantly increased ClC-2 transcript stability. Using Ussing chamber experiments, we demonstrate that IFN-gamma activates a pH-regulated and Cd(2+)-sensitive short circuit current, characteristic properties of the ClC-2 Cl(-) channel. These data suggest that IFN-gamma activates ClC-2 channel activity in lung epithelial cells via mRNA stabilization.

Animals↗

PubMed2004

CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity.

BACKGROUND: Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. METHODS: The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). RESULTS: PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. CONCLUSIONS: CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity.

Adult↗

PubMed2004

Inhibition of CLC-2 chloride channel expression interrupts expansion of fetal lung cysts.

Normal lung morphogenesis is dependent on chloride-driven fluid transport. The molecular identity of essential fetal lung chloride channel(s) has not been elucidated. CLC-2 is a chloride channel, which is expressed on the apical surface of the developing respiratory epithelium. CLC-2-like pH-dependent chloride secretion exists in fetal airway cells. We used a 14-day fetal rat lung submersion culture model to examine the role of CLC-2 in lung development. In this model, the excised fetal lung continues to grow, secrete fluid, and become progressively cystic in morphology (26). We inhibited CLC-2 expression in these explants, using antisense oligonucleotides, and found that lung cyst morphology was disrupted. In addition, transepithelial voltage (V(t)) of lung explants transfected with antisense CLC-2 was inhibited with V(t) = -1.5 +/- 0.2 mV (means + SE) compared with -3.7 +/- 0.3 mV (means + SE) for mock-transfected controls and -3.3 +/- 0.3 mV (means + SE) for nonsense oligodeoxynucleotide-transfected controls. This suggests that CLC-2 is important for fetal lung fluid production and that it may play a role in normal lung morphogenesis.

Animals↗

PubMed2004

Management of acute asthma exacerbations by general practitioners: a cross-sectional observational survey.

BACKGROUND: General practitioners (GPs) have a central place in the management of asthma, particularly in the context of acute exacerbations. AIM: To evaluate the management of asthma exacerbations by GPs, and to investigate the ability of risk factors for near fatal asthma to predict the severity of asthma attacks in the community. DESIGN OF STUDY: A 1-month multicentre cross-sectional survey. SETTING: One thousand and ninety-four GPs of the French Sentinel Network were contacted; 365 responded. METHOD: Asthma exacerbations were classified according to severity at presentation. Univariate and multivariate analyses were performed by logistic regression to identify those factors associated with severe exacerbations. RESULTS: Exacerbations were described in 219 patients with asthma. Over half (54%) of exacerbations were severe. Peak expiratory flow was recorded during the consultation in 55% of patients who were more than 5 years old. beta(2) agonists were prescribed to 93% of patients, systemic corticosteroids to 71%, and antibiotics to 64%. Only 42% of patients had a written action plan for self-management of exacerbations. Risk factors for near fatal asthma, identified in 26% of patients, were not significantly associated with severe asthma exacerbations. Short duration of exacerbation before consultation (<3 hours) was associated with an increase in relative risk of severe exacerbation of 3.38, 95% confidence intervals (CIs) = 1.19 to 9.61, compared with duration of >3 hours. CONCLUSION: Risk factors for near fatal asthma identified in previous studies were not predictive of a severe exacerbation in general practice, with the exception of short duration of exacerbation before consultation. This suggests that new methods to predict risk in the outpatient settings should be developed.

Acute Disease↗

PubMed2003

Environmental allergens and asthma in urban elementary schools.

BACKGROUND: Asthma in school children is rising, and indoor allergens are very common triggers of asthma attacks; however, the risk of the school environment on asthma has not been well studied. OBJECTIVE: To determine the presence and the levels of common aeroallergens in schools, where asthma prevalence rates are high. METHODS: Settled dust samples were collected from 12 Baltimore City public elementary schools, and they were analyzed for the following allergens: cockroaches (Bla g 1/2), dust mites (Der f 1/p 1), dog (Can f 1), cat (Fel d 1), and mouse (Mus m 1). School asthma prevalence rates were correlated with allergen levels, and association between allergen levels and other risk factors present in the schools' environment was examined. RESULTS: The mean and range levels were 1.49 U/g (0 to 8) for Bla g 1/2; 0.38 microg/g (0 to 11.9) for the Der f 1/p 1; 1.44 microg/g (0.1 to 9.6) for Can f 1; 1.66 microg/g (0.2 to 12) for Fel d 1; and 6.24 microg/g (0.3 to 118.3) for Mus m 1. Dust mite, cat and dog allergens were significantly in rooms with carpet and/or area rugs, compared to rooms with bare floors (P < 0.05). Asthma prevalence rates varied from 11.8 to 20.8% between schools and positively correlation with the mean levels of Bla g 1/2 in the schools (P = 0.001). CONCLUSIONS: Common allergens that are known to trigger asthma were detected in all school environments, where asthma prevalence rates were high. However, the overall allergen levels were low, indicating that other factors, including exposures in the homes of asthmatic patients, may have more relevance to sensitization and symptoms than school exposures.

Air Pollutants↗

PubMed2002

Using seasonal variations in asthma hospitalizations in children to predict hospitalization frequency.

Asthma hospitalization rates have increased in the United States since 1980. The exposure risk of many environmental factors, which contribute to respiratory disease, vary throughout the year. The objective of this study was to investigate the seasonal variation of pediatric asthma hospitalizations and predict hospitalization frequency. This was a longitudinal analysis of all pediatric asthma hospitalizations in the state of Maryland by age, gender, race, and residence using non-confidential discharge data sets from 1986 to 1999. Of the 631,422 pediatric hospitalizations in the state of Maryland during the years 1986-1999, 45,924 (7%) had a primary admission diagnosis of asthma. Frequency of hospitalization for asthma was lowest in the summer in all age groups, and highest in the fall. Seasonal variation in severe asthma episodes was least striking in children aged 15-18. This was in contrast to non-asthma admissions, which were highest in winter in preschool children, but relatively flat in school- and teenaged children. Using neural network modeling, weekly asthma hospitalizations could be predicted with an R2 between 0.71 and 0.8. Temporal trends in asthma hospitalizations were seen in each age group, gender, race, and location. The seasonal variability in asthma hospitalizations suggests that acute asthma is influenced by variables beyond socioeconomic factors and adherence to medical regimens. Strategies to combat exacerbations of asthma should take into consideration seasonal effects on a population. In addition, temporal trends examined over many years can be used to predict frequency of severe asthma episodes in a population.

Adolescent↗

PubMed2002

ClC-5: ontogeny of an alternative chloride channel in respiratory epithelia.

Chloride transport is critical to many functions of the lung. Molecular defects in the best-known chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR), lead to impaired function of airway defensins, hydration of airway surface fluid, and mucociliary clearance leading to chronic lung disease, and premature death, but do not cause defects in lung development. We examined the expression of one member of the ClC family of volume- and voltage-regulated channels using the ribonuclease protection assay and Western blot analysis in rats. ClC-5 mRNA and protein are most strongly expressed in the fetal lung, and expression is maintained although downregulated postnatally. In addition, using immunocytochemistry, we find that ClC-5 is predominantly expressed along the luminal surface of the airway epithelium, suggesting that ClC-5 may participate in lung chloride secretion. Identifying candidate genes for critical ion transport functions is essential for understanding normal lung morphogenesis and the pathophysiology of several lung diseases. In addition, the manipulation of non-CFTR chloride channels may provide a viable approach for treating cystic fibrosis lung disease.

Aging↗

PubMed2002

Reported adverse drug events in infants and children under 2 years of age.

OBJECTIVE: To characterize risks to infants and young children from drugs and biological products that were identified in spontaneous adverse event reports submitted to the US Food and Drug Administration. METHODS: Of >500 000 MedWatch adverse event reports received by the Food and Drug Administration from November 1997 through December 2000, we identified 7111 reports about infants and children younger than age 2. The reports were analyzed for health outcome (eg, death, hospitalization, congenital anomaly), principal suspect drug, and whether the route of drug exposure was direct administration or through the mother in the perinatal period. RESULTS: Drug therapy was associated with an average of 243 reported deaths annually over the 38-month study period, with 100 (41%) occurring during the first month of life and 204 (84%) during the first year. In 1432 (24%) reported adverse event cases of all levels of severity, exposure to the drug was from the mother during pregnancy, delivery, or lactation. Although 1902 different drugs, biological products, and other chemicals were identified in the reports, only 17 drugs or biological products were a suspect in 54% of all serious and fatal adverse events in drugs administered directly. CONCLUSION: Adverse reactions to drug therapy are a significant cause of death and injury in infants and children under 2 years of age. Drugs administered to the mother in the perinatal period constituted a major route of exposure to adverse drug advents. These results underscore the need for additional drug testing in the youngest pediatric patients and for carefully weighing the risks versus benefits of medication.

Adverse Drug Reaction Reporting Systems↗

PubMed2002

The adolescent with asthma: strategies for improved outcomes.

Asthma is a chronic disease that affects millions of Americans. Evaluation and treatment guidelines have been developed by panels of experts for over 10 years. Management of the teen with asthma, however, creates special opportunities for the practitioner, because of the transition of adolescents from dependence on the family to an increased desire for independence. This article will review our current understanding of the special needs of the adolescent asthmatic, and make recommendations for improving disease control.

Adolescent↗