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Biomedical subjects

Paul D Scanlon

Publications and source records attributed to Paul D Scanlon.

11 recordsLinked to original sources
PubMed2006

Genetic association analysis of functional impairment in chronic obstructive pulmonary disease.

RATIONALE: Patients with severe chronic obstructive pulmonary disease (COPD) may have varying levels of disability despite similar levels of lung function. This variation may reflect different COPD subtypes, which may have different genetic predispositions. OBJECTIVES: To identify genetic associations for COPD-related phenotypes, including measures of exercise capacity, pulmonary function, and respiratory symptoms. METHODS: In 304 subjects from the National Emphysema Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically plausible candidate genes. Regression models were used to test for association, using a test-replication approach to guard against false-positive results. For significant associations, effect estimates were recalculated using the entire cohort. Positive associations with dyspnea were confirmed in families from the Boston Early-Onset COPD Study. RESULTS: The test-replication approach identified four genes-microsomal epoxide hydrolase (EPHX1), latent transforming growth factor-beta binding protein-4 (LTBP4), surfactant protein B (SFTPB), and transforming growth factor-beta1 (TGFB1)-that were associated with COPD-related phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (p < or = 0.03) and in LTBP4 (p < or = 0.03) were associated with maximal output on cardiopulmonary exercise testing. Markers in LTBP4 (p < or = 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were associated with carbon monoxide diffusing capacity (p < or = 0.04). Three SNPs in TGFB1 were associated with dyspnea (p < or = 0.002), one of which replicated in the family study (p = 0.02). CONCLUSIONS: Polymorphisms in several genes seem to be associated with COPD-related traits other than FEV(1). These associations may identify genes in pathways important for COPD pathogenesis.

Aged↗
PubMed2005

Neurohumoral activation as a link to systemic manifestations of chronic lung disease.

COPD is a major cause of death and disability worldwide. Treatment of COPD improves lung function but is unlikely to slow the steady downhill course of the disease or reduce mortality. In COPD, numerous abnormalities can be found outside the lung. These include systemic inflammation, cachexia, and skeletal muscle dysfunction. Thus, COPD has been called a systemic disease. Convincing data demonstrate that COPD causes neurohumoral activation. By precedents derived from chronic heart failure and other diseases characterized by neurohumoral activation, we propose that the negative consequences of neurohumoral activation, namely inflammation, cachexia, effects on ventilation, and skeletal muscle dysfunction, give rise to a self-perpetuating cycle that contributes to the pathogenesis of COPD, and which may involve respiratory muscle dysfunction as well as systemic inflammation. This concept may further help explain the increased cardiovascular morbidity and mortality in COPD patients. Currently, little is known about the effect of treatments directed at neurohumoral activation and COPD. As this aspect of COPD becomes better understood, new insights may direct novel therapeutic approaches.

Aldosterone↗
PubMed2004

Loss of bone density with inhaled triamcinolone in Lung Health Study II.

Inhaled glucocorticosteroids (ICS) are commonly prescribed for chronic obstructive pulmonary disease. No adverse effect on bone mineral density (BMD) has been proven. In a randomized double-blind, placebo-controlled trial at seven centers in North America, we recruited 412 current smokers or recent quitters with mild to moderate chronic obstructive pulmonary disease. They used inhaled triamcinolone acetonide, 600 mcg, or placebo, twice daily. We measured femoral neck and lumbar spine BMD at baseline and after 1 and 3 years, and serum osteocalcin at baseline, 3 months, 1 year, and 3 years. After 3 years, BMD at the femoral neck decreased 1.78% more with ICS than with placebo (p < 0.001). More participants in the ICS group experienced 6% or more loss of femoral neck BMD (p = 0.002). Lumbar spine BMD increased in the placebo group by 0.98% but decreased by 0.35% in the ICS group (a difference of 1.33%, p = 0.007). Changes in osteocalcin did not correlate with changes in BMD. Fractures, lost height, or osteoporosis diagnoses were not increased among ICS users compared with placebo users. In summary, the use of inhaled triamcinolone acetonide was associated with loss of BMD at the femoral neck and lumbar spine after 3 years of treatment.

Administration, Inhalation↗
PubMed2004

Clinical significance of elevated diffusing capacity.

STUDY OBJECTIVE: Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) is used as a pulmonary function test (PFT) to assess gas transfer in the lungs. The implications of a low DLCO are well-recognized, but the clinical significance of a high DLCO is not clear. The aim of this study was to identify the clinical correlates of a high DLCO. PATIENTS AND METHODS: We identified 245 patients with a high DLCO (ie, > 140% predicted) and a matched group of 245 patients with normal DLCO (ie, 85 to 115% predicted), who were selected from a laboratory database of 45,000 patients tested between January 1997 and December 1999. We compared the demographic features, clinical diagnoses, and PFT data between the two groups. SETTINGS: Large multispecialty group practice. RESULTS: The patients in the high DLCO group were heavier (mean [+/- SD] weight, 96.0 +/- 22.9 vs 85.0 +/- 21.3 kg, respectively; p < 0.001), had a higher mean body mass index (32.9 +/- 7.4 vs 29.4 +/- 6.4 kg/m(2), respectively; p < 0.001), larger body surface area (p < 0.001), and larger mean total lung capacity (p = 0.007) and alveolar volume (p < 0.001). The clinical diagnoses of obesity (p < 0.001) and asthma (p < 0.001) were more common among patients with high DLCO values. The majority of patients (62%) with a high DLCO had a diagnosis of obesity, asthma, or both. Polycythemia, hemoptysis, and left-to-right shunt were uncommon. CONCLUSION: A high DLCO on a PFT is most frequently associated with large lung volumes, obesity, and asthma. Other conditions are much less common. A clinical condition, which typically reduces DLCO, may deceptively normalize DLCO in such patients.

Adult↗
PubMed2003

Outcome results of a school-based screening program for undertreated asthma.

BACKGROUND: Undertreatment of asthma is associated with significant potentially preventable morbidity, including frequent school absences. Guideline dissemination and clinician education have met with variable success. School-based identification of children with potentially undertreated asthma may provide an alternative strategy for improving asthma management in children. OBJECTIVE: To evaluate the effectiveness of school-based identification of potentially undertreated asthma. METHODS: A controlled trial of school-based identification of children with known but symptomatic asthma using mailed parent surveys, letters recommending medical follow-up, and medical record review to evaluate changes in asthma treatment after referral. RESULTS: Most parents (79.9%, n = 5,116 respondents) responded to the survey and 19.4% (n = 994) of children were reported to have a physician diagnosis of asthma or reactive airway disease. Letters of referral were sent to 489 children with parent-reported asthma who were identified as having potentially undertreated asthma. Approximately one-third (31.2%, n = 153) of these children had physician visits, and 92 (18.8% of all referred) had documented medication changes. In addition, there were 20 new physician diagnoses in this group of children. In the control group of 604 children with asthma, there were significantly fewer children with asthma-related visits (131, 21.7%, P = 0.0004) and children with medication changes (74, 12.3%, P = 0.002) in a comparable 6-month window. CONCLUSIONS: School-based screening or case identification increased the number of physician asthma-related visits and changes in asthma therapy.

Adolescent↗
PubMed2003

Lack of long-term adverse adrenal effects from inhaled triamcinolone: Lung Health Study II.

STUDY OBJECTIVE: Inhaled corticosteroids (ICS) are widely used in the treatment of COPD. One of the potential adverse effects of their use is the development of adrenal suppression. Our study aimed to determine the effects of ICS on adrenal function over 3 years of use in patients with COPD. METHODS: Two hundred twenty-one subjects were recruited from the 1,116 patients already enrolled in Lung Health Study II and were randomized to receive either triamcinolone, 1,200 microg, or placebo daily. Basal cortisol levels and cortisol levels at 30 min and 60 min following cosyntropin injection were measured at study entry and after 1 year and 3 years of participation. RESULTS: Basal cortisol levels in the placebo group were higher than in those receiving active drug at all time points and rose through the study period. There was no suppression of cortisol levels after cosyntropin stimulation at any study point in any subgroup. CONCLUSION: Use of inhaled triamcinolone, 1,200 microg/d, over 3 years does not suppress baseline adrenal function or diminish adrenal responsiveness to cosyntropin stimulation.

Administration, Inhalation↗
PubMed2003

Current practice in pulmonary function testing.

More than 30 million Americans have chronic obstructive pulmonary disease (COPD) and asthma, with internists, pediatricians, and family physicians providing most of their medical care. Recent management guidelines for asthma and COPD recommend regular use of spirometry for the diagnosis and management of these disorders. Because of the development of easy-to-use office-based spirometers, an increasing number of physicians have ready access to spirometry. Beyond simple spirometry, various tests are available from many pulmonary function laboratories for more detailed evaluation of patients with respiratory disorders. For these reasons, all physicians who care for patients with pulmonary disease must understand basic pulmonary function testing and have a fundamental understanding of more sophisticated tests. A series of performance standards has been developed for improved accuracy and precision of pulmonary function tests. Physicians responsible for administering and interpreting pulmonary function tests, even simple spirometry, must be aware of relevant guidelines. This concise review addresses current indications for pulmonary function testing, provides an overview of the studies commonly available in modern pulmonary function laboratories, and includes comments on basic interpretation and testing standards.

Asthma↗
PubMed2002

Prognostic factors, clinical course, and hospital outcome of patients with chronic obstructive pulmonary disease admitted to an intensive care unit for acute respiratory failure.

OBJECTIVE: To describe prognostic factors, clinical course, and hospital outcome of patients with chronic obstructive pulmonary disease admitted to an intensive care unit for acute respiratory failure. DESIGN: Analysis of prospectively collected data. SETTING: A multidisciplinary intensive care unit of an inner-city university hospital. PATIENTS: Patients with chronic obstructive pulmonary disease admitted to an intensive care unit for acute respiratory failure from August 1995 through July 1998. MEASUREMENTS AND MAIN RESULTS: Data were obtained concerning demographics, arterial blood gas, Acute Physiology and Chronic Health Evaluation (APACHE) II score, sepsis, mechanical ventilation, organ failure, complications, and hospital mortality rate. Fifty-nine percent of patients were male, 63% white, and 36% African-American; the mean age was 63.1 +/- 8.9 yrs. Noninvasive mechanical ventilation was tried in 40% of patients and was successful in 54% of them. Invasive mechanical ventilation was required in 61% of the 250 admissions. Sepsis developed in 31% of patients, nonpulmonary organ failure in 20%, pneumothorax in 3%, and acute respiratory distress syndrome in 2%. Multiple organ failure developed in 31% of patients with sepsis compared with 3% without sepsis (p <.0001). Predicted and observed hospital mortality rates were 30% and 15%, respectively. Differences in age and arterial carbon dioxide and oxygen tensions between survivors and nonsurvivors were not significant. Arterial pH was lower in nonsurvivors than in survivors (7.21 vs. 7.25, p =.0408). The APACHE II-predicted mortality rate (p =.0001; odds ratio, 1.046; 95% confidence interval, 1.022-1.070) and number of organ failures (p <.0001; odds ratio, 5.524; 95% confidence interval, 3.041-10.031) were independent predictors of hospital outcome; invasive mechanical ventilation was not an independent predictor. CONCLUSIONS: Physiologic abnormalities at admission to an intensive care unit and development of nonrespiratory organ failure are important predictors of hospital outcome for critically ill patients with chronic obstructive pulmonary disease who have acute respiratory failure. Improved outcome would require prevention and appropriate treatment of sepsis and multiple organ failure.

Acute Disease↗