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Abstract 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.

Spatial relationships between clinical data for pediatric asthmatics (hospital and emergency department utilization rates), and socioeconomic and urban characteristics in Baltimore City were analyzed with the aim of identifying factors that contribute to increased asthma rates. Socioeconomic variables and urban characteristics derived from satellite data explained 95% of the spatial variation in hospital rates. The proportion of families headed by a single female was the most important variable accounting for 89% of the spatial variation. Evidence suggests that the high rates of hospital admissions and emergency department (ED) visits may partially be due to the difficulty of single parents with limited resources managing their child's asthma condition properly. This knowledge can be used for education towards mitigating ED and hospital events in Baltimore City. [ABSTRACT FROM AUTHOR]

Background: Demyelinating diseases (DD) are a group of chronic neurological diseases associated with loss and injury of brain or spinal cord regions. These conditions could trigger impairment of neurological functions and disability from earlier stages of life. Epidemiological data on DD remains insufficient for decision-making in the Mexican healthcare system. This study aims to describe the epidemiology of DD based on data from Mexico's National Registry of Demyelinating Diseases., Methods: A cross-sectional, registry-based, observational study was performed. We analyzed 408 reports of multiple sclerosis (331, 81%), neuromyelitis optica spectrum disorder (67, 16%), chronic recurrent inflammatory optic neuropathy (5, 1%), clinically isolated syndrome (4, 0.9%), and autoimmune encephalitis (1, 0.2%) reported across 2021., Results: The time from first symptoms to diagnosis of any DD was about 3 years. A treatment failure history was detected in 40% of patients. It was estimated that NMOSD accounts for 20% of all disorders. There was evidence that the use of brand-name and generic IFN drug products lead to increased therapeutic failures., Conclusion: Our research team suggests reinforcing educational programs and activities based on diagnosis and clinical management improvement to first-contact physicians and specialty doctors and promoting awareness in the whole population., Competing Interests: Declaration of Competing Interest All authors wish to declare that have nothing to disclose. There are no competing interest(s) or conflict of interest that may be perceived to influence the results and discussion reported in this paper. All authors or their institutions did not receive payment or services from a third party (government, commercial, or private foundation) for any aspect of the submitted work at any time. The funding for the writing and editing process was carried out and supported by Unidad de Investigación en Salud (UIS). Each author filled and signed an electronic ICMJE form for disclosure of potential conflicts of interest and was responsible for the accuracy and completeness of the submitted information. If editors need to confirm this asseveration, the corresponding author may share this information separately. This document was designed to improve delivering of this information since all electronic ICMJE forms have the statement as “nothing to disclose”., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Since ancient times, massage therapy has been used to promote healing by people of all backgrounds and cultures. Massage therapy was once taught as a core nursing skill, but it gradually lost ground in the United States during the second half of the 20th century with the increased use of technology and documentation in nursing. In recent years, however, there has been a resurgence in the use of massage therapy. Research has provided insight into the mechanisms by which massage supports the healing process, and this has sparked support for including massage therapy in routine hospital care. In this article, the authors touch on the history of massage in nursing care and discuss its emotional and physiologic benefits for both patient and nurse. They describe specific massage techniques and discuss precautions to consider before using massage with certain patients.

Background: The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining "exacerbation" or about how to characterize an episode's severity., Objective: National Institutes of Health institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies., Methods: We used comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health-organized workshop in March 2010 and finalized in September 2011., Results: No dominant definition of "exacerbation" was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalizations, and (3) use of short-acting β-agonists as quick-relief (sometimes referred to as "rescue" or "reliever") medications., Conclusions: The working group participants propose that the definition of "asthma exacerbation" be "a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome." As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Furthermore, they propose the development of a standardized, component-based definition of "exacerbation" with clear thresholds of severity for each component., (Published by Mosby, Inc.)

Objective: To investigate the association between sleep disordered breathing (SDB) and parent report of attention and behavioral problems in children, as well as the association between sleep stage duration and measures of child functioning in a clinically referred sample., Methods: A chart review was conducted of 95 children with clinical history of SDB who completed an overnight polysomnography study in a pediatric sleep laboratory. Child functioning was assessed at the time of the sleep study by parent report on the Child Behavior Checklist (CBCL). The apnea hypopnea index was used as a measure of SDB severity., Results: The apnea hypopnea index was associated with externalizing behavior, but not attention problems on the CBCL. In children 2-3 years old, stage 4 sleep duration was associated with externalizing behavior. In children 4-16 years old, REM sleep duration was associated with externalizing behavior., Conclusions: Children with increased SDB severity may be at greater risk for behavioral problems. Differences between the association of sleep stages and externalizing behavior in toddlers compared with older children suggests possible developmental differences in the association between sleep and behavior.

The Division of Lung Diseases of the National Heart, Lung and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences; mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease (PVD); sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases, (2) injury, regeneration, and repair in the developing lung, (3) PVD in children, (4) development and adaptation of ventilatory responses to postnatal life, (5) nonatopic wheezing: aberrant large airway development or injury? (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases, and (7) predictive and personalized medicine for children., (Copyright 2008 Wiley-Liss, Inc.)

Purpose. To evaluate the impact of transition to managed care from fee for service on asthma service utilization among Maryland Medicaid insured children. Methods. Healthcare claims from 1997-2000 for children with asthma insured by Maryland Medicaid were extracted and analyzed. Results. Between 1997-2000, inhaled corticosteroid use increased as a proportion of all asthma medications. Outpatient asthma visits increased from 4.2% to 5.9% of all outpatient claims as both asthma-related hospitalizations and emergency department visits decreased. Conclusions. Restructuring of Maryland Medicaid for children from fee for service to managed care was associated with improvement in asthma-related healthcare utilization claims.

The reasons for significant disparities in asthma mortality are unclear. Maryland vital statistics and medical examiner data were used to examine timing, location, and circumstances of asthma deaths. We found that unexplained deaths increased substantially over the past 10 years and that young, male, and black asthmatics were more likely to die before hospital admission. Factors contributing to disparities included better availability of anti-inflammatory medications among whites versus blacks, and a higher incidence of positive toxicology screens among males versus females. Disparities in asthma mortality might be reduced through efforts to optimize asthma treatment and reduce illicit drug use.

Asthma is a chronic disease that can result in exacerbations leading to urgent care in emergency departments (EDs) and hospitals. We examined seasonal and temporal trends in pediatric asthma ED (1997-1999) and hospital (1986-1999) admission data so as to identify periods of increased risk of urgent care by age group, gender, and race. All pediatric ED and hospital admission data for Maryland residents occurring within the state of Maryland were evaluated. Distinct peaks in pediatric ED and hospital asthma admissions occurred each year during the winter-spring and autumn seasons. Although the number and timing of these peaks were consistent across age and racial groups, the magnitude of the peaks differed by age and race. The same number, timing, and relative magnitude of the major peaks in asthma admissions occurred statewide, implying that the variables affecting these seasonal patterns of acute asthma exacerbations occur statewide. Similar gross seasonal trends are observed worldwide. Although several environmental, infectious, and psychosocial factors have been linked with increases in asthma exacerbations among children, thus far they have not explained these seasonal patterns of admissions. The striking temporal patterns of pediatric asthma admissions within Maryland, as described here, provide valuable information in the search for causes.

Background: Clinical pathways for asthma are tools that have the potential to improve compliance with nationally recognized management guidelines, but their effect on patient outcomes has not been documented., Objectives: To determine the effect of an asthma clinical pathway on patients' length of stay, use of nebulized beta-agonist therapy while hospitalized, and use of acute care clinics for 2 weeks after discharge., Design/methods: The study was a randomized, controlled trial. Patients between the ages of 2 and 18 years admitted with an asthma exacerbation and not under the care of an asthma specialist were eligible for the study. Patients were randomized either to a conventional ward (control group) or to a ward using the clinical pathway (intervention group). For 2 weeks after discharge, we collected data to determine whether patients visited a health care provider for worsening asthma., Results: One hundred ten patients (26%) were enrolled. Control and intervention groups had similar demographic and asthma severity profiles. The intervention group had an average length of stay 13 hours shorter than did the control group. In addition, at every dosing interval, the intervention group received less nebulized beta-agonist therapy. There were no deaths in either group., Conclusion: A clinical pathway for inpatient asthma decreased the length of stay and beta-agonist medication use with no adverse outcomes or increased acute-care encounters through 2 weeks after discharge.

Objective: To evaluate the accuracy of the pulse oximeter to detect hypoxemia in patients with sickle cell disease in an ambulatory care setting., Study Design: Simultaneous measurements of PaO(2), arterial oxygen saturation by co-oximetry (criterion standard), and pulse oximetry were performed in 21 children with sickle cell disease during 22 outpatient visits. The bias and precision of the pulse oximeter compared with measured arterial oxygen saturation by co-oximetry were determined. The sensitivity, specificity, and positive and negative predictive values of the pulse oximeter to detect hypoxemia (PaO(2) <70 mm Hg) were also calculated., Results: The mean difference between pulse oximetry and measured oxygen saturation (bias) was 5.0% and the SD (precision) was 5.3. Twenty-one patients had a PaO(2) greater than 70 mm Hg; 7 of these (33%) were predicted to be hypoxic by pulse oximetry with values less than 93%, for a specificity to detect normoxia of 67%., Conclusion: Making treatment decisions based on pulse oximetry data alone in patients with sickle cell disease who are not acutely ill may be inappropriate.

The fetal lung actively transports chloride across the airway epithelium. ClC-2, a pH-activated chloride channel, is highly expressed in the fetal lung and is located on the apical surface of the developing respiratory epithelium. Our goal was to determine whether acidic pH could stimulate chloride secretion in fetal rat distal lung epithelial cells mounted in Ussing chambers. A series of acidic solutions stimulated equivalent short-circuit current (I(eq)) from a baseline of 28 +/- 4.8 (pH 7.4) to 70 +/- 5 (pH 6.2), 114 +/- 12.8 (pH 5.0), and 164 +/- 19.2 (pH 3.8) microA/cm(2). These changes in I(eq) were inhibited by 1 mM cadmium chloride and did not result in large changes in [(3)H]mannitol paracellular flux. Immunofluorescent detection by confocal microscopy revealed that ClC-2 is expressed along the luminal surface of polarized fetal distal lung epithelial cells. These data suggest that the acidic environment of the fetal lung fluid could activate chloride channels contributing to fetal lung fluid production and that the changes in I(eq) seen in these Ussing studies may be due to stimulation of ClC-2.

Mutations in the chloride channel, ClC-5, have been described in several inherited diseases that result in the formation of kidney stones. To determine whether ClC-5 is also involved in calcium homeostasis, we investigated whether ClC-5 mRNA and protein expression are modulated in rats deficient in 1alpha,25(OH)(2) vitamin D(3) with and without thyroparathyroidectomy. Parathyroid hormone (PTH) was replaced in some animals. Vitamin D-deficient, thyroparathyrodectomized rats had lower serum and higher urinary calcium concentrations compared with control animals as well as lower serum PTH and calcitonin concentrations. ClC-5 mRNA and protein levels in the cortex decrease in vitamin D-deficient, thyroparathyroidectomized rats compared with both control and vitamin D-deficient animals. ClC-5 mRNA and protein expression increase near to control levels in vitamin D-deficient, thyroparathyroidectomized rats injected with PTH. No significant changes in ClC-5 mRNA and protein expression in the medulla were detected in any experimental group. Our results suggest that PTH modulates the expression of ClC-5 in the kidney cortex and that neither 1alpha,25(OH)(2) vitamin D(3) nor PTH regulates ClC-5 expression in the medulla. The pattern of expression of ClC-5 varies with urinary calcium. Animals with higher urinary calcium concentrations have lower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption.

Keratinocyte growth factor (KGF) is mitogenic for epithelial cells and induces cystic dilation of fetal lung explants through cystic fibrosis transmembrane conductance regulator-independent chloride channels. One candidate fetal lung chloride channel that is highly expressed on the apical surface of the respiratory epithelium and markedly downregulated after birth is CLC-2. We hypothesized that KGF regulates CLC-2 expression in the fetal lung. Primary fetal rat distal lung epithelial cell monolayers were grown in medium containing 10 ng/ml KGF for 48 h. CLC-2 protein was increased by Western blot analysis of whole-cell lysates in KGF-treated cultures. Similarly, KGF stimulated CLC-2 messenger RNA (mRNA) by Northern blot analysis. This enhanced expression was dose-dependent and maximal at 48 h with 10 ng/ml KGF. Promoter-reporter gene experiments demonstrated that KGF did not stimulate gene transcription. By inhibition of new mRNA synthesis with actinomycin D, evidence was obtained that KGF stabilizes CLC-2 mRNA. We speculate that KGF may positively influence pulmonary chloride and fluid secretion by a secondary pathway affecting CLC-2 degradation.

Mechanisms responsible for regulation of pulmonary epithelial chloride-channel expression in the perinatal period are under investigation to better understand normal lung development and airway disease pathogenesis. The ClC-2 epithelial chloride channel is regulated by changes in pH and volume and is most abundant in lung during fetal development. In this study, we identify and sequence the ClC-2 promoter, which is GC rich and lacks a TATA box. By construction of a series of promoter-luciferase constructs, a 67-bp GC box-containing sequence in the promoter is shown to be critical to ClC-2 expression in primary and immortalized fetal lung epithelial cells. Electrophoretic mobility shift assays and antibody supershifts demonstrate that the Sp1 and Sp3 transcription factors are expressed in fetal lung nuclei and interact with the GC box sequences in the promoter. Immunoblotting techniques demonstrate that Sp1 and Sp3 are perinatally downregulated in the lung with the same temporal sequence as ClC-2 downregulation. This work suggests that Sp1 and Sp3 activate ClC-2 gene transcription and that reduction in Sp1 and Sp3 at birth explains perinatal downregulation of ClC-2 in the lung.

Cystic fibrosis (CF) is a lethal inherited disease that results from abnormal chloride conduction in epithelial tissues. ClC-2 chloride channels are expressed in epithelia affected by CF and may provide a key "alternative" target for pharmacotherapy of this disease. To explore this possibility, the expression level of ClC-2 channels was genetically manipulated in airway epithelial cells derived from a cystic fibrosis patient (IB3-1). Whole-cell patch-clamp analysis of cells overexpressing ClC-2 identified hyperpolarization-activated Cl- currents (HACCs) that displayed time- and voltage-dependent activation, and an inwardly rectifying steady-state current-voltage relationship. Reduction of extracellular pH to 5.0 caused significant increases in HACCs in overexpressing cells, and the appearance of robust currents in parental IB3-1 cells. IB3-1 cells stably transfected with the antisense ClC-2 cDNA showed reduced expression of ClC-2 compared with parental cells by Western blotting, and a significant reduction in the magnitude of pH-dependent HACCs. To determine whether changes in extracellular pH alone could initiate chloride transport via ClC-2 channels, we performed 36Cl- efflux studies on overexpressing cells and cells with endogenous expression of ClC-2. Acidic extracellular pH increased 36Cl- efflux rates in both cell types, although the ClC-2 overexpressing cells had significantly greater chloride conduction and a longer duration of efflux than the parental cells. Compounds that exploit the pH mechanism of activating endogenous ClC-2 channels may provide a pharmacologic option for increasing chloride conductance in the airways of CF patients.