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Biomedical subjects

E Rand Sutherland

Publications and source records attributed to E Rand Sutherland.

At least 19 recordsLinked to original sources
PubMed2006

Obesity and asthma.

Asthma and obesity are prevalent disorders, each with a significant public health impact, and a large and growing body of literature suggests an association between the two. The systemic inflammatory milieu in obesity leads to metabolic and cardiovascular complications, but whether this environment alters asthma risk or phenotype is not yet known. Animal experiments have evaluated the effects of leptin and obesity on airway inflammation in response to both allergic and nonallergic exposures and suggest that airway inflammatory response is enhanced by both endogenous and exogenous leptin. Cross-sectional and prospective cohort studies of humans have shown a modest overall increase in asthma incidence and prevalence in the obese, although body mass index does not appear be a significant modifier of asthma severity. Studying the obesity-asthma relationship in large cohorts, in which self-reports are frequently used to ascertain the diagnosis of asthma, has been complicated by alterations in pulmonary physiology caused by obesity, which may lead to dyspnea or other respiratory symptoms but do not fulfill accepted physiologic criteria for asthma. Recent investigations toward elucidating a shared genetic basis for these two disorders have identified polymorphisms in specific regions of chromosomes 5q, 6p, 11q13, and 12q, each of which contains one or more genes encoding receptors relevant to asthma, inflammation, and metabolic disorders, including the beta(2)-adrenergic receptor gene ADRB2 and the glucocorticoid receptor gene NR3C1. Further research is warranted to synthesize these disparate observations into a cohesive understanding of the relationship between obesity and asthma.

Adipocytes↗
PubMed2005

Nocturnal asthma.

Nocturnal symptoms and overnight decrements in lung function are a common part of the asthma clinical syndrome. As many as 75% of asthmatic subjects are awakened by asthma symptoms at least once per week, with approximately 40% experiencing nocturnal symptoms on a nightly basis. An extensive body of research has demonstrated that nocturnal symptoms of cough and dyspnea are accompanied by circadian variations in airway inflammation and physiologic variables, including airflow limitation and airways hyperresponsiveness. Alterations in beta2-adrenergic and glucocorticoid receptors and hypothalamic-pituitary-adrenal axis function might play a role in modulating the nocturnal asthma phenotype, and recent studies have suggested that melatonin, a neurohormonal controller of circadian rhythms, might be important as well. Treatment strategies in nocturnal asthma are similar to those used in persistent asthma, although dosing of medications to target optimum effect during periods of nocturnal worsening is beneficial.

Asthma↗
PubMed2005

Nocturnal asthma: underlying mechanisms and treatment.

Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV(1)) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma. Nocturnal symptoms are a common part of the asthma clinical syndrome; up to 75% of asthmatics are awakened by asthma symptoms at least once per week, and approximately 40% experience nocturnal symptoms on a nightly basis. An extensive body of research has demonstrated that nocturnal symptoms such as cough and dyspnea are accompanied by increases in airflow limitation, airway hyperresponsiveness, and airway inflammation. Treatment strategies in nocturnal asthma are similar to those used in persistent asthma, although dosing of medications to target optimum delivery during periods of nocturnal worsening is beneficial.

Asthma↗
PubMed2005

Airway fibroblasts exhibit a synthetic phenotype in severe asthma.

BACKGROUND: Platelet-derived growth factor (PDGF) may have a significant role in airway remodeling in asthma, because it is a powerful inductor of many airway fibroblast activities such as collagen synthesis. OBJECTIVE: To determine whether PDGF is a significant contributor to airway remodeling in patients with asthma by enhancing airway fibroblast procollagen I expression. METHODS: Six normal controls without asthma, 10 subjects with mild to moderate asthma, and 5 subjects with severe asthma underwent bronchoscopy with endobronchial biopsy. Biopsies were placed in Dulbecco modified Eagle medium and fibroblasts cultured in the presence and absence of PDGF isoforms -AA, -BB, and -AB (1, 5, 10, 100 ng/mL) and insulin-like growth factor 1 (100 ng/mL). Fibroblast procollagen I and PDGF receptors (PDGFRs) alpha and beta expression were determined by ELISA. RESULTS: Platelet-derived growth factor BB significantly enhanced fibroblast procollagen I expression in patients with severe asthma compared with patients with mild/moderate asthma and normal controls. Furthermore, the baseline fibroblast expression of PDGFR-beta was significantly greater in patients with severe asthma compared with the other groups. CONCLUSION: This pilot study suggests that airway fibroblasts from patients with severe asthma exhibit a synthetic phenotype, which may be driven by the overexpression of PDGFR-beta.

Adult↗
PubMed2005

Maximum exercise as an outcome in COPD: minimal clinically important difference.

Limitation of physical activity occupies a central role in the symptom complex of patients with chronic obstructive pulmonary disease (COPD), and improvement in exercise capacity is a key outcome of response to COPD therapy. Maximum exercise capacity testing facilitates assessment of physiologic mechanisms of exercise and allows quantitation of the degree of limitation. This manuscript utilizes published data from the National Emphysema Treatment Trial to investigate the minimal clinically important difference (MCID) in maximum exercise capacity in patients with severe emphysema. Distribution- and opinion-based methods were used to estimate MCID. Expert clinician opinion yielded a value of 10 Watts as the MCID for change in maximum exercise capacity. Baseline standard deviation and error data yielded a one-half standard deviation-based estimate of 10.5 Watts and a standard error-based estimate of 4.2 Watts. In subjects randomized to medical therapy, the mean (+/-SD) 24-month change in maximum exercise capacity following medical therapy was -9.2 +/- 1.2 Watts, whereas among those randomized to lung volume reduction surgery, mean 24-month change in maximum exercise capacity was 1.7 +/- 17.7 Watts, with a mean difference between the groups of 10.9 Watts. The observed difference in maximum exercise capacity after 24 months between subjects randomized to medical versus surgical therapy conforms to both opinion- and distribution-based estimates of MCID. Further investigation is needed to develop and validate estimates of MCID for maximum exercise capacity and other key clinical outcomes in COPD.

Aged↗
PubMed2004

Physiologic correlates of distal lung inflammation in asthma.

BACKGROUND: The distal lung is an important site of inflammation in asthma. Maximal midexpiratory flows and the ratio of maximal:partial flows are purported to reflect distal lung function. OBJECTIVE: We obtained contemporaneous transbronchial biopsy, spirometry, and plethysmography to describe more accurately the relationship between physiology and distal lung inflammation in asthma. METHODS: Ten patients with severe, persistent asthma with mean +/- SE FEV(1) of 2.8 +/- 0.2 L and overnight fall in FEV(1) of 22.8% +/- 3.8% underwent transbronchial biopsy, spirometry, maximal midexpiratory flows, maximal:partial ratio, and lung volumes, all at 4 am. Morphometric analysis was performed after immunohistochemistry for eosinophils, lymphocytes, macrophages, mast cells, and neutrophils. RESULTS: Maximal midexpiratory flows, maximal:partial ratio, FEV(1), and forced vital capacity were not significantly correlated with alveolar tissue inflammation. However, the degree of eosinophilic alveolar inflammation was significantly and positively correlated with both total lung capacity (Spearman rho=0.70; P=.03) and thoracic gas volume (rho=0.62; P=.05). Correlation between eosinophils and other lung volumes was not observed. Other inflammatory cell types did not correlate with lung volumes. CONCLUSION: Purported physiologic measures of distal lung function are poorly correlated with histopathologic evidence of distal lung inflammation. Measurement of lung volumes more accurately reflects eosinophilic distal lung inflammation.

Adult↗
PubMed2004

Outpatient treatment of chronic obstructive pulmonary disease: comparisons with asthma.

Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of expiratory airflow limitation caused by chronic inflammation of the airways and lung parenchyma. The airway inflammatory response in COPD is initiated by smoking in the overwhelming majority of cases, and chronic exposure to cigarette smoke initiates a series of events that cause damage to central airways, peripheral airways, and terminal airspaces, leading to physiologic and clinical abnormalities. The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy. The outpatient treatment of COPD differs from the approach used in asthma and can be divided into 3 subgroups: health care maintenance, drug therapy, and nondrug therapy. Smoking cessation, regular spirometry, and immunization are important components of health care maintenance. Drug therapy consists of optimal bronchodilator therapy supplemented, when necessary, with either inhaled corticosteroids or theophylline. Nondrug therapies include pulmonary rehabilitation, supplemental oxygen, and surgery.

Ambulatory Care↗
PubMed2004

Atypical bacterial pneumonia and asthma risk.

The role of respiratory infections in asthma is poorly understood. Atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae are present in the lower airways of approximately 50% of asthmatics. This study tested the hypothesis that early life community-acquired pneumonia caused by Mycoplasma pneumoniae or Chlamydia pneumoniae is associated with increased asthma prevalence. Thirty-five subjects with a history of community-acquired pneumonia (22 due to atypical bacteria, 13 due to nonatypical pathogens) were evaluated by questionnaire 7-9 years after the episode of pneumonia. Subjects with a history of either typical or atypical pneumonia demonstrated increased asthma prevalence. Current or past asthma prevalence was 55% in subjects with atypical bacterial pneumonia and 61.5% in subjects with nonatypical bacterial pneumonia. Significant between-group differences were not demonstrated with regard to asthma prevalence (risk ratio=0.89; 95% confidence interval=0.49-1.61), current bronchodilator use [1.18 (0.44-3.17)], and family history of atopy [1.18 (0.73-1.91)], or asthma [1.63 (0.68-3.88)]. These data suggest that atypical bacterial pneumonia confers a risk of asthma similar to that seen with nonatypical bacterial pneumonia. Prospective studies are warranted to more fully evaluate the importance of atypical bacterial pneumonia as an asthma risk factor.

Adolescent↗
PubMed2003

Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF.

IL-3, IL-5, and GM-CSF are related hematopoietic cytoines that are important for allergic inflammation. The receptors for human IL-5, IL-3, and GM-CSF are members of the hematopoietin receptor superfamily and are comprised of a cytokine-specific alpha chain and the common beta chain that is shared among these cytokines for signaling. Each of these cytokines contributes to the differentiation and function of leukocyte subpopulations and have clinical importance in protective immunity and in the pathophysiology of a spectrum of immunologic diseases that are as diverse as allergy and asthma, pulmonary alveolar proteinosis, neurodegenerative diseases, and malignancies. Delineating the biology of these cytokines is enabling the development of new strategies for diagnosing and treating these diseases and modulating immune responses.

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

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↗