The accuracy of methods employed to measure the elastin-specific crosslinks, desmosine (DES) and isodesmosine (IDES), has been called into question because contaminants in the urine may cause elevated values. In the present study urine samples were spiked with a known amount of [14C]DES and refluxed in 6 N HCl. Sephadex G-15 chromatography of the hydrolyzed urine was employed to remove contaminants. DES and IDES were quantified by high performance liquid chromatography (HPLC) as well as by amino acid analysis. The amount of isotope recovered was used to determine losses during the overall procedure and the isotope dilution to calculate the amounts of endogenous DES and IDES originally present in the urine. Because similar values were obtained by both methods, the more rapid HPLC method was used for all succeeding analyses. In one experiment, the DES amounts in urine collected from hamsters for 3 days after intratracheal treatment with human neutrophil elastase (300 µg) or porcine pancreatic elastase (300 µg) were 0.212 ± 0.012 (mean ± SEM, two measurements on a single pool) and 0.816 ± 0.005 (two measurements) µg per hamster per day, respectively. Urine from control hamsters had a mean value of 0.074 ± 0.008 (eight measurements) µg per hamster per day. The HNE- and PPE-treated hamsters had mean linear intercept values of 119 and 159% of control values, respectively, giving a positive correlation between increase in airspace size and elevation of urinary DES. For eight normal men 25 to 68 yr of age who were never-smokers, mean ± SEM 24-h urinary values were 13.3 ± 2.3 µg DES and 11.3 ± 1.7 µg IDES; DES/creatinine and IDES/creatinine ratios were 6.5 ± 0.7 µg and 5.5 ± 0.4 µg per g creatinine, respectively. Values for subjects remained constant when measured on urine collected on different days. Hamster and human DES values are as much as 20-fold and 10-fold lower, respectively, than previously reported values. This assay should prove useful in studying conditions when DES excretion may be elevated.
Background: COPD patients are at increased risk for venous thromboembolism (VTE). VTE however remains under-diagnosed in this population and the clinical profile of VTE in COPD is unclear. Methods: Global initiative for chronic Obstructive Lung Disease (GOLD) stages II-IV participants in the COPD G
Background . The outcomes for outpatient treatment of acute exacerbations of COPD (AECOPD) are poorly described. Design . The results of a daily diary recording symptoms and peak flows were compiled into a severity score to trigger algorithm-based treatments and a symptom index to follow treatment response. Treatment failure (symptom index failing to return to baseline for 2 consecutive days or hospitalization within 21 days) was the main outcome. Results . Twenty-two patients (FEV 1 0.81 ± 0.26 L) were treated for 115 AECOPDs (corticosteroids = 36, antibiotics = 41, corticosteroids/antibiotics = 38). Treatment failure was 50% for the corticosteroid/antibiotic compared to 28% () for the corticosteroid and 34% () for the antibiotic group. Patients suffering from AECOPDs treated with corticosteroids had dyspnea, wheezing, and decreased peak flow; those treated with antibiotics had sputum symptoms; those treated with corticosteroids/antibiotics had dyspnea, wheezing, sputum symptoms, and decreased peak flows. Conclusions . AECOPDs with both dyspnea and sputum symptoms are more refractory to standard treatment and likely require closer monitoring.
Asthma has a tendency to destabilize at night in patients that are diurnaly active and try to sleep at night. As asthma worsens, the expression of this disease seems to increase at night. Additionally, nocturnal asthmatics have increased airway hyperresponsiveness and likely more active inflammation at night as compared with the daytime. Although the cause of nocturnal asthma cannot be completely explained, there do appear to be a variety of internal body circadian rhythms that play a role in this disease. Also, noncircadian rhythmic influences such as sleep, supine posture, snoring, and gastroesophageal reflux cannot be dismissed. Directing therapy, perhaps in unique ways, may be essential for the control of nocturnal asthma. Patients on inhaled corticosteroid therapy or nonsteroidal anti-inflammatory agents often persist in asthmatic disease expression at night. Long-acting bronchodilator therapy, either by inhalation or with sustained-release tablets, is often added to inhaled anti-inflammatory therapy for more complete 24-hour disease control. Using existing therapies but employing chronotherapeutic strategies is likely to improve the overall asthma management. By focusing on nocturnal asthma, we may be able to improve our understanding of this disease and more effectively control it over each 24-hour period.
Background: COPD patients are at increased risk for venous thromboembolism (VTE). VTE however remains under-diagnosed in this population and the clinical profile of VTE in COPD is unclear. Methods: Global initiative for chronic Obstructive Lung Disease (GOLD) stages II-IV participants in the COPD G
Asthma is an inflammatory disease of the airways characterized by intermittent symptoms, including chest congestion, cough, and wheezing. These symptoms are associated with airway responsiveness and variable airflow obstruction. This chapter focuses on the traditional asthma topics of pathogenesis, diagnosis, and treatment, and discusses the environmental issues important to asthma. It explores asthma symptom prevention and enhanced control of disease, and also discusses the effects of exercise, occupation, stress, and pregnancy on asthma. Airway narrowing leading to increased airway resistance, and airflow obstruction in asthma occurs through three major mechanisms: airway smooth muscle contraction; increased airway lumen debris; and airway wall thickening from inflammation, edema, and over time, fibrosis. Multiple mechanisms produce airway inflammation, and they involve a variety of interactions between pro-inflammatory and inflammatory mediators. Measurements of airflow are known not to be strongly related to asthma symptoms but provide a more objective and additional measure to evaluate asthma control.
