Biomedical subjects

Misoo C Ellison

Publications and source records attributed to Misoo C Ellison.

At least 19 recordsLinked to original sources

PubMed2006

Depression, fatigue, and pain in systemic lupus erythematosus (SLE): relationship to the American College of Rheumatology SLE neuropsychological battery.

OBJECTIVE: To examine the frequency and reliability of depression, fatigue, and pain self-report measures in patients with systemic lupus erythematosus (SLE) and healthy controls, and to examine the relationship between a cognitive impairment index (CII) derived from the American College of Rheumatology neuropsychology research battery of tests for SLE (ACR-SLE battery) and measures of depression, pain, fatigue, and perceived cognitive dysfunction. METHODS: Thirty-one patients with SLE with a history of overt neuropsychiatric symptoms (neuropsychiatric SLE [NPSLE]), 22 patients with SLE without overt neuropsychiatric symptoms (non-NPSLE), and 25 healthy controls completed the following measures at baseline and 1-month followup: ACR-SLE battery, perceived cognitive difficulties, depression, fatigue, and pain. RESULTS: Patients with SLE (both NPSLE and non-NPSLE) showed higher symptoms of depression, higher levels of fatigue, greater pain, and more perceived cognitive problems. All measures except the Center for Epidemiologic Studies Depression scale (CES-D) demonstrated adequate reliability across the SLE groups at retest. Only patients with NPSLE had significant correlations between CII and depression, fatigue, and pain. Neither the non-NPSLE patients nor the controls had significant relationships with the CII and these behavioral measures. CONCLUSION: Patients with SLE report higher levels of cognitive difficulties, depression, pain, and fatigue compared with controls. Reliability for all measures, except the CES-D, was established in the SLE group. Overall, results suggest that cognitive dysfunction, pain, fatigue, and depression in patients with NPSLE may represent global changes in the central nervous system that require ongoing evaluation and treatment.

Adult↗

PubMed2006

Surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry to identify patients with chronic obstructive pulmonary disease.

There are currently no blood tests to identify the majority of smokers at risk for chronic obstructive pulmonary disease (COPD). We used plasma protein profiles from surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry to identify a panel of protein biomarkers that can distinguish patients with COPD from closely matched controls. Plasma was obtained from 30 COPD subjects and 30 controls matched for age, sex, and smoking history. Plasma protein profiles were generated using Cu2+-immobilized metal affinity capture (IMAC) and strong anion exchanger (Q10) protein chips. Classification and regression tree (CART) analysis identified a panel of 5 biomarkers using the IMAC protein chip that could distinguish COPD patients from controls with sensitivity and specificity of 91.67% and 88.33%, respectively. The 10-fold cross-validation yielded 81.67% sensitivity and 81.67% specificity. This demonstrates the feasibility of using SELDI as a diagnostic test for COPD; however, larger cohorts will be needed to validate these biomarkers and determine their predictive value longitudinally.

Algorithms↗

PubMed2006

Proteomics in pulmonary medicine.

Proteomics is the study of the entire protein complement of the genome (the proteome) in a biological system. Proteomic studies require a multidisciplinary approach and have only been practical with the convergence of technical and methodologic improvements including the following: advances in mass spectrometry and genomic sequencing that now permit the identification and relative quantization of small amounts (femtomole) of nearly any single protein; new methods in gel electrophoresis that allow the detection of subtle changes in protein expression, including posttranslational modifications; automation and miniaturization that permit high-throughput analysis of clinical samples; and new bioinformatics and computational methods that facilitate analysis and interpretation of the abundant data that are generated by proteomics experiments. This convergence makes proteomics studies practical for pulmonary researchers using BAL fluid, lung tissue, blood, and exhaled breath condensates, and will facilitate the research of complex, multifactorial lung diseases such as acute lung injury and COPD. This review describes how proteomics experiments are conducted and interpreted, their limitations, and how proteomics has been used in clinical pulmonary medicine.

Humans↗

PubMed2006

Improvements in distal lung function correlate with asthma symptoms after treatment with oral montelukast.

STUDY OBJECTIVES: The distal airways are likely to contribute to asthma pathobiology and symptoms but have rarely been specifically evaluated in relation to systemic oral therapy. We hypothesized that treatment with montelukast, an oral cysteinyl-leukotriene receptor antagonist, would improve both proximal and distal lung physiology in patients with mild asthma. DESIGN: Randomized, double-blind, crossover design. SETTING: Academic referral center. PATIENTS: Subjects with mild asthma limited to using short-acting inhaled beta(2)-agonists. INTERVENTIONS: Nineteen subjects with mild asthma underwent a baseline assessment of lung function, lung mechanics, and symptoms, followed by randomization to therapy with montelukast, 10 mg taken in the evening, or placebo in a crossover, double-blind fashion. Each treatment phase lasted 4 weeks, with a 2-week washout period. A repeat evaluation was performed during the last week of each treatment phase. MEASUREMENTS AND RESULTS: Montelukast resulted in improvement in (mean +/- SD) proximal and distal lung function parameters (change in FEV(1): montelukast, 0.16 +/- 0.06 L; placebo, -0.05 +/- 0.05 L; p = 0.008); change in specific conductance: montelukast, 7.2 +/- 2.9% predicted; placebo, -17 +/- 8% predicted; p = 0.007; change in % predicted residual volume [RV]: montelukast, 18.4 +/- 8.3% predicted; placebo, 3.0 +/- 2.9% predicted; p = 0.05). Improvement in symptoms (ie, wheeze and chest tightness) correlated with improvements in RV while receiving montelukast, but not while receiving placebo (Pearson coefficients: 0.55 and 0.66, respectively; p < 0.008 and 0.04, respectively). CONCLUSIONS: The systemically acting oral agent montelukast improves proximal and distal lung physiology. Improvements in distal lung function correlate with improvements in asthma symptoms.

Acetates↗

PubMed2005

Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency.

Patients who have common variable immunodeficiency (CVID) and granulomatous/lymphocytic interstitial lung disease (GLILD) are at high risk for early mortality and B cell lymphomas. Infection with human herpes virus type 8 (HHV8), a B cell lymphotrophic virus, is linked to lymphoproliferative disorders in people who have secondary immunodeficiencies. Therefore, we determined the prevalence of HHV8 infection in CVID patients with GLILD. Genomic DNA isolated from peripheral blood mononuclear cells was screened by nested- and real time-quantitative PCR (QRT-PCR) for the presence of HHV8 genome. It was positive in 6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID-control), and no patients receiving intravenous gamma globulin (n = 13) or normal blood donors (n = 20). Immunohistochemistry (IHC) demonstrated expression of the latency-associated nuclear antigen-1 (LANA-1) in the biopsies of the lung, liver, and bone marrow of four patients with CVID-GLILD. One CVID-GLILD patient developed a B cell lymphoma during the course of the study. QRT-PCR demonstrated high copy number of HHV8 genome and IHC showed diffuse staining for LANA-1 in the malignant lymph node. HHV8 infection may be an important factor in the pathogenesis of the interstitial lung disease and lymphoproliferative disorders in patients with CVID.

Adult↗

PubMed2005

Short-term impact of a randomized multifaceted intervention for wheezing infants in low-income families.

OBJECTIVE: To present an interim analysis of the effect of a home-based intervention with low-income caregivers of wheezing infants at risk for childhood asthma on mediating variables. METHOD: Infants aged 9 to 24 months with 3 or more physician-documented wheezing episodes were randomly assigned to environmental support intervention (ES) (n = 90) or control (n = 91) groups. Nurse home visitors intervened for 1 year to decrease allergen and environmental tobacco smoke exposure and improve symptom perception and management. Assessments at baseline and 12 months included allergens in house dust, infant urinary cotinine levels, caregivers' symptom reports, quality of life, illness management, and quality of caregiving. Medical records were coded for hospitalizations, emergency department visits, and corticosteroid bursts. RESULTS: Within the ES group, cockroach allergen levels were significantly reduced and there was a trend toward reduction in dog dander levels. Among infants with detectable urinary cotinine, levels were significantly reduced in the ES group. Caregiver psychological resources modified the impact, and low-resource ES caregivers were the most strongly affected. Asthma knowledge and provider collaboration improved significantly in the ES group. Neither reports of infant symptoms nor emergency department visits or hospitalizations showed positive intervention effects. Number of corticosteroid bursts for infants was significantly higher for the ES group. CONCLUSIONS: The Childhood Asthma Prevention Study intervention was effective in reducing several environmental exposures and improving illness management. However, even with an intensive home-based intervention, we failed to reduce respiratory symptoms or medical use in the ES group relative to the control group, illustrating the difficulty of changing the course of early asthma development among low-income infants.

Adrenal Cortex Hormones↗

PubMed2005

Responder cell frequency estimation and binomial three-level nonlinear mixed effects model in limiting dilution assays.

Responder cell frequencies (RCF), which describe vaccine-boosted immune responses in herpes zoster (HZ) prevention studies, have been estimated by using limiting dilution assays (LDA). The theoretical linearity assumption between the logarithm of the proportion of nonresponding wells (s) and the cell concentration (N) (or dilution level) in LDA, based on the single-hit Poisson model, is often violated with observed data resulting in biased estimates of RCF. In this article, the Poisson assumption is modified by applying a mixture of Poisson and gamma distributions, resulting in a negative binomial assumption, which presents a better fit between s and N. In LDA for HZ prevention studies, binary responses (responder or non-responder wells) are measured repeatedly at different cell concentrations and over time. To account for the correlation between responses to varying dilution levels from individuals, and the correlation between repeated assays of individuals over time simultaneously, a binomial three-level nonlinear mixed-effects model is proposed. For parameter estimation, a maximum likelihood method is applied via adaptive Gaussian quadrature. There is a lack of non-Gaussian multilevel nonlinear mixed-effects software, which can execute such a complicated fit. In this article, an algorithm for the three-level nonlinear mixed-effects model, which can be inserted into the code in the SAS procedure NLMIXED, is suggested.

Cell Count↗

PubMed2005

Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data.

OBJECTIVE: To correlate cognitive dysfunction with structural and neurometabolic brain findings in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). BACKGROUND: Over 25% of non-NPSLE patients have cognitive dysfunction, but the cerebral basis of this observation is not well understood. METHOD: Seven patients with non-NPSLE and seven control subjects were given a series of neuropsychological tests and neuroimaging with magnetic resonance imaging and magnetic resonance spectroscopy. Analyses of cognitive function and structural and neurometabolic measures of the brain were performed. RESULTS: Compared with controls, the non-NPSLE patients were significantly impaired on a global cognitive impairment index (CII). No significant differences between the groups were found in choline/creatine (Ch/Cr), N-acetylaspartic acid/Cr, or hippocampal volumes. Ch/Cr was highly associated with CII across the sample. CONCLUSIONS: This is the first study to correlate cognitive impairment with an increase in Ch/Cr ratio among patients with SLE. These results, although preliminary, suggest that changes in cerebral white matter may be important in determining the subtle cognitive impairment that may occur in patients with SLE, even in the absence of neuropsychiatric symptoms.

Adult↗

PubMed2005

Macrophages kill human papillomavirus type 16 E6-expressing tumor cells by tumor necrosis factor alpha- and nitric oxide-dependent mechanisms.

The expression of adenovirus serotype 2 or 5 (Ad2/5) E1A sensitizes cells to killing by NK cells and activated macrophages, a property that correlates with the ability of E1A to bind the transcriptional coadaptor proteins p300-CBP. The E6 oncoproteins derived from the high-risk human papillomaviruses (HPV) interact with p300 and can complement mutant forms of E1A that cannot interact with p300 to induce cellular immortalization. Therefore, we determined if HPV type 16 (HPV16) E6 could sensitize cells to killing by macrophages and NK cells. HPV16 E6 expression sensitized human (H4 and C33A) and murine (MCA-102) cell lines to lysis by macrophages but not by NK cells. The lysis of cells that expressed E6 by macrophages was p53 independent but dependent on the production of tumor necrosis factor alpha (TNF-alpha) or nitric oxide (NO) by macrophages. Unlike cytolysis assays with macrophages, E6 expression did not significantly sensitize cells to lysis by the direct addition of NO or TNF-alpha. Like E1A, E6 has been reported to sensitize cells to lysis by TNF-alpha by inhibiting the TNF-alpha-induced activation of NF-kappaB. We found that E1A, but not E6, blocked the TNF-alpha-induced activation of NF-kappaB, an activity that correlated with E1A-p300 binding. In summary, Ad5 E1A and HPV16 E6 sensitized cells to lysis by macrophages. Unlike E1A, E6 did not block the ability of TNF-alpha to activate NF-kappaB or sensitize cells to lysis by NK cells, TNF-alpha, or NO. Thus, there appears to be a spectrum of common and unique biological activities that result as a consequence of the interaction of E6 or E1A with p300-CBP.

Animals↗

PubMed2005

Improved neurobehavioral functioning in emphysema patients following lung volume reduction surgery compared with medical therapy.

STUDY OBJECTIVES: The goal of this study was to evaluate the neuropsychological and psychological functioning of emphysema patients following lung volume reduction surgery (LVRS) compared with patients receiving only medical therapy (MT). DESIGN: Patients with moderate-to-severe emphysema who were enrolled in the National Emphysema Treatment Trial at two sites (National Jewish Medical and Research Center and Ohio State University) were given a neuropsychological battery at baseline, 6 to 10 weeks later (following participation in pulmonary rehabilitation), and at 6 months following randomization to either LVRS or MT treatment. SUBJECTS AND MEASUREMENTS: Twenty patients randomized to MT, 19 patients randomized to LVRS, and 39 matched, healthy control subjects completed a battery of tests that measured cognitive functioning, depression, anxiety, and quality of life (QoL). RESULTS: Controlling for practice, patients in the LVRS treatment arm at the 6-month follow-up demonstrated significant improvement compared with MT patients in cognitive tasks involving sequential skills and verbal memory. The LVRS patients also showed significant reductions in depression compared with the MT patients, as well as improved physical and psychosocial QoL. Correlational analysis indicated that improved immediate verbal memory in the LVRS group was related to improved QoL. No associations were found between changes in cognitive function and changes in depression, exercise performance, or pulmonary functioning. CONCLUSION: Patients who received LVRS demonstrated improvement in specific neuropsychological functions, depression, anxiety, and QoL scores compared with patients with continued MT treatment 6 months following randomization. However, mechanisms for these neurobehavioral changes are unclear. Improved verbal memory and sequential skills following LVRS were not directly associated with depression or exercise capacity. Nonetheless, LVRS led to a strong and likely clinically significant improvement in neuropsychological functioning over and above that explained by practice effects or MT. This finding adds to the growing list of clinical benefits of LVRS over MT, and supports additional research into the underlying mechanisms of this therapeutic effect.

Colorado↗

PubMed2004

Reliability and validity of the proposed American College of Rheumatology neuropsychological battery for systemic lupus erythematosus.

OBJECTIVE: To examine the reliability and validity of the proposed American College of Rheumatology (ACR) neuropsychological battery for patients with systemic lupus erythematosus (SLE). METHODS: Thirty-one SLE patients with a history of neuropsychiatric symptoms (NPSLE), 22 SLE patients without a history of neuropsychiatric symptoms (non-NPSLE), and 25 healthy controls completed measures of cognition at baseline and after 1 month. The 1-hour proposed ACR-SLE battery was compared with a 4-hour comprehensive battery (CB). RESULTS: Seven of 12 measures from the ACR-SLE battery were lower in SLE patients compared with controls. Overall agreement between impairment on the ACR-SLE battery and the CB was 90%. This was established using previously defined impairment on the CB and 4 of 12 scores impaired on the ACR-SLE battery. Almost perfect agreement between the 2 batteries was found for non-NPSLE patients and healthy controls (95-96%) and moderate agreement was reported for NPSLE patients (81%). Intraclass correlation coefficients for ACR-SLE tests ranged from 0.40 to 0.90, indicating adequate reliability. CONCLUSION: Reliability and validity of the ACR-SLE battery was established in this study. Agreement regarding classification for impairment was almost perfect for non-NPSLE and moderate for the NPSLE patients. The ACR battery is well designed for general classification of cognitive impairment in SLE. However, comprehensive testing may be useful in identifying specific deficits in NPSLE.

Adult↗

PubMed2004

Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and an inability to make specific antibodies. OBJECTIVE: We sought to determine the prevalence, clinical characteristics, and effect on survival of noninfectious pulmonary disease in patients with CVID. METHODS: A retrospective analysis of 69 patients with CVID was performed. Patients were divided into 3 groups on the basis of the type of pulmonary disease present: group 1 (n=29), no pulmonary disease; group 2 (n=23), chronic respiratory symptoms without diffuse radiographic abnormalities; and group 3 (n=18), chronic respiratory symptoms and diffuse radiographic abnormalities. Group 3 patients were divided into 2 subgroups on the basis of the histopathologic pattern seen on biopsy. Group 3A (n=13) included patients with granulomatous lung disease, lymphocytic interstitial pneumonia, follicular bronchiolitis, and lymphoid hyperplasia, a group of syndromes referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Group 3B (n=5) consisted of patients with all other types of interstitial lung disease (ILD). RESULTS: Fifty-eight percent of patients with CVID had noninfectious pulmonary complications. Group 3A (GLILD) patients had worse prognosis than the other groups, with a median survival of 13.7 versus 28.8 years (P<.001). Lymphoproliferative disease occurred in 31% of patients with GLILD. GLILD was associated with the presence of dyspnea (P<.05); splenomegaly (P<.05); restrictive pulmonary physiology; consolidation, ground-glass, and reticular radiographic abnormalities; and low CD3+ (P<.05) and CD8+ cell populations (P<.01). CONCLUSION: ILD is common in patients with CVID. The presence of GLILD was associated with a worse prognosis and increased prevalence of lymphoproliferative disorders.

Adult↗

PubMed2004

Lung inflation with direct injection of agarose: a technique for simultaneous molecular and morphometric measurements.

The usual methods for preparing lungs for morphologic study involve the instillation of fixatives that modifyproteins and RNA such that the tissue is unsuitable for molecular studies. To develop a technique suitable for molecular studies, pieces of adult rat lungs were infiltrated with agarose, glutaraldehyde, or paraformaldehyde and the consistency of alveolar inflation was compared to lungs inflated with 10% formalin. Only direct injection with 1% agarose resulted in comparable inflation of lung tissue and preserved RNA and protein. Thus, this technique enables simultaneous molecular and morphometric analysis of the lung on small pieces of lung tissue in heterogeneous lung diseases.

Animals↗

PubMed2003

A catalytic antioxidant attenuates alveolar structural remodeling in bronchopulmonary dysplasia.

Superoxide anion and other oxygen-free radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia. We tested the hypothesis that a catalytic antioxidant metalloporphyrin AEOL 10113 can protect against hyperoxia-induced lung injury using a fetal baboon model of bronchopulmonary dysplasia. Fetal baboons were delivered by hysterotomy at 140 days of gestation (term = 185 days) and given 100% oxygen for 10 days. Morphometric analysis of alveolar structure showed that fetal baboons on 100% oxygen alone had increased parenchymal mast cells and eosinophils, increased alveolar tissue volume and septal thickness, and decreased alveolar surface area compared with animals given oxygen as needed. Treatment with AEOL 10113 (continuous intravenous infusion) during 100% oxygen exposure partially reversed these oxygen-induced changes. Hyperoxia increased the number of neuroendocrine cells in the peripheral lung, which was preceded by increased levels of urine bombesin-like peptide at 48 hours of age. AEOL 10113 inhibited the hyperoxia-induced increases in urine bombesin-like peptide and numbers of neuroendocrine cells. An increasing trend in oxygenation index over time was observed in the 100% oxygen group but not the mimetic-treated group. These results suggest that AEOL 10113 might reduce the risk of pulmonary oxygen toxicity in prematurely born infants.

Animals↗

PubMed2003

Elevated serum melatonin is associated with the nocturnal worsening of asthma.

BACKGROUND: Increased airway inflammation at night contributes to the nocturnal worsening of asthma. In vitro studies have shown exogenous melatonin to be pro-inflammatory in asthma, but it is unknown whether endogenous melatonin levels are a controller of airway inflammation in nocturnal asthma. OBJECTIVE: Our aim was to determine 24-hour patterns of serum melatonin and their relationship to overnight decline in physiology in subjects with nocturnal asthma, non-nocturnal asthma, and in healthy controls. METHODS: Observational study of pulmonary physiology and melatonin levels in patients with nocturnal asthma (n = 7), non-nocturnal asthma (n = 13), and healthy controls (n = 11). Subjects maintained a constant sleep-wake regimen for 7 days. On day 8, serum melatonin was measured every 2 hours by radioimmunoassay and analyzed by cosinor modeling. The correlation between serum melatonin levels and overnight change in spirometry was evaluated by Spearman's rank correlation analysis. RESULTS: In subjects with nocturnal asthma, peak melatonin levels were significantly elevated compared with healthy controls (67.6 +/- 5.0 pg/mL versus 53.5 +/- 4.0 pg/mL, P =.03). Melatonin acrophase was delayed in nocturnal asthma (02:54 versus 01:58 in healthy controls, P =.003, and 02:15 in non-nocturnal asthma, P =.01). In subjects with nocturnal asthma, increasing melatonin levels were significantly and inversely correlated with overnight change in FEV(1) (r = -.79, P =.04), a relationship that was not observed in non-nocturnal asthma or healthy controls. CONCLUSIONS: Nocturnal asthma is associated with elevation and phase delay of peak serum melatonin levels. Elevated melatonin levels might contribute to the pathogenesis of nocturnal asthma.

Adult↗

PubMed2003

Sequence-specific targeting of two bases on both DNA strands by the somatic hypermutation mechanism.

Somatic mutations within antibody genes alter the affinity and selectivity of antibody molecules and largely define the quality of the memory B cell repertoire in many vertebrate species. While some evidence supports the idea that there is a strand bias to the hypermutation mechanism, conflicting data suggest that somatic mutations are initially acquired on both strands of DNA. In this study, we utilized a previously defined trinucleotide target bias of hypermutation to address the question of target strand symmetry during mutation. Mutabilities of specific base positions within all triplets were compared between the two strands of DNA in three divergent databases of hypermutated sequences. Unexpectedly, we consistently observed strong correlations between mutabilities of triplet positions on the two DNA strands only for G and T in the first position of a triplet or for C and A in the last position. The most straightforward interpretation of this result is that the mutation mechanism targets either G and T or C and A on both strands of DNA with a frequency that depends upon the adjacent dinucleotide sequence. In view of published evidence that C is targeted by the hypermutation mechanism, we can extrapolate that C and A are specifically targeted at a frequency that depends upon the preceding 5' dinucleotide.

Animals↗

PubMed2003

Minimizing attrition in a long-term clinical trial of pediatric asthma.

BACKGROUND: Despite increased attention focused on the need to prevent patient attrition in long-term clinical trials, high dropout rates have threatened the success of numerous studies. OBJECTIVE: To evaluate the disease, demographic, and psychological factors associated with missed visits and study dropout to help improve patient management in long-term clinical trials. METHODS: Predictors of attrition were examined within the Childhood Asthma Management Program (CAMP), a large, multicenter clinical trial that followed up 1,041 children with asthma for 4 to 6 years. RESULTS: Eighty-two percent of patients attended all study visits. The tendency to miss visits was increased among older children with milder asthma, lower intellectual and social competence, and more symptoms of behavioral problems and emotional distress. Forty-two patients who missed 3 or more visits in a row and did not attend the final visit were considered study dropouts; these patients at baseline had milder asthma; lower cognitive, academic, and social competence skills; and more family conflict and distress than found among participants who remained in the study. The 49 children who had erratic attendance but did not drop out also had lower intellectual and academic skills and less family social support. CONCLUSIONS: The 4% dropout rate in CAMP was lower than reported in any previous long-term asthma trial. The findings of milder disease, decreased psychological resources, and increased distress in problem-attendance patients can assist in identifying patients who are at risk for missed visits or dropout during the trial either to block their entry into the trial or to focus efforts at maintaining their attendance once enrolled in the trial.

Anti-Asthmatic Agents↗

PubMed2003

Altered pituitary-adrenal interaction in nocturnal asthma.

BACKGROUND: Increased airway inflammation at night contributes to the nocturnal worsening of asthma, but the mechanisms regulating circadian variations in airway inflammation are unknown. OBJECTIVE: We hypothesized that altered hypothalamic-pituitary-adrenal axis function serves as an endogenous controller of inflammation in nocturnal asthma. METHODS: Patients with nocturnal asthma (n = 7), patients with nonnocturnal asthma (n = 13), and healthy control subjects (n = 11) adhered to a regular sleep-wake cycle for 1 week. Corticotropin and cortisol levels were assayed every 2 hours for 24 hours. Low-dose corticotropin stimulation was performed. Circadian hormonal flux was analyzed by means of cosinor modeling and calculation of the area under the 24-hour curve. RESULTS: Corticotropin peak levels and areas under the 24-hour curve were significantly increased in patients with nocturnal asthma versus values in patients with nonnocturnal asthma and control subjects. Patients with nonnocturnal asthma demonstrated significantly increased areas under the 24-hour cortisol curve when compared with control subjects, but peak cortisol levels did not differ between groups. Cortisol levels after low-dose corticotropin stimulation did not differ between groups. Corticotropin and cortisol levels were not correlated with the degree of physiologic impairment. CONCLUSION: Nocturnal asthma is marked by increased corticotropin levels that are not accompanied by commensurate increases in cortisol levels. This observation might indicate blunted adrenal responsiveness in the nocturnal asthma phenotype. Conversely, adrenal response to corticotropin might be enhanced in nonnocturnal asthma, attenuating nocturnal worsening of airway inflammation.

Adrenocorticotropic Hormone↗