elastin and Bronchiectasis

Topics: Aged; Bronchiectasis; Collagen Diseases; Dermis; Dermoscopy; Diagnosis, Differential; Elastin; Female; Humans; Pseudoxanthoma Elasticum

Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes. Over the past couple of years, multidimensional scoring systems such as the Bronchiectasis Severity Index have been introduced to predict disease severity and mortality. Although there are currently no licensed therapies for bronchiectasis, an increasing number of clinical trials are planned or ongoing. While this emerging evidence is awaited, bronchiectasis guidelines will continue to be informed largely by real-life evidence from observational studies and patient registries. Key developments in the bronchiectasis field include the establishment of international disease registries and characterisation of disease phenotypes using cluster analysis and biological data.

Topics: Bronchiectasis; Cluster Analysis; Comorbidity; Elastin; Humans; Inflammation; Leukocyte Elastase; Phenotype; Prognosis; Radiography; Severity of Illness Index

Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p< or =0.05). The highest desmosine levels were found in subjects with alpha1-antitrypsin deficiency, bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a short-term longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days). In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy.

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin Deficiency; Bronchiectasis; Cross-Linking Reagents; Cross-Sectional Studies; Cystic Fibrosis; Desmosine; Elastin; Electrophoresis, Capillary; Emphysema; Extracellular Matrix; Female; Humans; Isodesmosine; Longitudinal Studies; Lung Diseases, Obstructive; Male; Middle Aged

It is hypothesized that emphysema develops in some severely alpha 1-antitrypsin (AAT)-deficient persons because endogenous elastases are not adequately controlled by AAT, and accelerated elastin degradation occurs. It is not known whether augmentation therapy with AAT diminishes degradation of lung elastin in severely deficient persons with lung disease. Two severely deficient, PiZ patients were studied, a 63-year-old never-smoking woman with bronchiectasis and a 41-year-old smoking man with emphysema. Urinary desmosine (DES) was determined before and after augmentation therapy with AAT, 260 mg/kg/month. Mean +/- SEM pretreatment urinary DES was elevated in both patients, 19.7 +/- 0.9 (n = 2) and 10.8 +/- 0.2 (n = 2) micrograms/g creatinine, respectively, compared to normal values of 7.5 +/- 0.3 (n = 22) micrograms/g creatinine. Following augmentation therapy, urinary DES values decreased 40 and 36%, respectively, to 11.9 +/- 0.3 (n = 8) and 6.9 +/- 0.4 (n = 7) microgram/g creatinine (p < 0.05). We conclude that monthly AAT augmentation therapy decreased DES excretion in the urine of these PiZ patients. We speculate that since there was lung disease in both patients, a decrease in degradation of lung elastin is the most likely explanation for this observation.

Topics: Adult; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Amino Acids; Bronchiectasis; Desmosine; Elastin; Emphysema; Female; Humans; Isodesmosine; Lung; Male; Middle Aged; Smoking

Severe airway lesions can result following exposure to various pathogens or toxic gases and can show a variety of pathologic lesions including necrotizing bronchitis, bronchiolitis and bronchiectasis. The purpose of this study was to develop a chronic airway lesion in the hamster, a species recognized for its lack of endogenous pulmonary disease. We have successfully adapted a technique of inducing rabbit airway lesions with nitric acid to the hamster lung and have characterized the morphologic, morphometric and biochemical features of the model. Following a transorotracheal instillation of 0.5% HNO3 in saline, Syrian golden hamsters showed during a 60-day study period a spectrum of airway changes including acute bronchitis, acute bronchiolitis, obliterative bronchiolitis, bronchiolectasia and bronchiectasis. Morphometric changes in the HNO3-treated hamsters included decreased lung volumes and decreased internal surface areas. Biochemical changes showed increases in lung weight and in total collagen and elastin. The model is useful because a prolonged insult to the airways develops rapidly and persists over a long period of time, important features for investigations designed to study the effects of superimposed insults upon pre-existent airway lesions.

Topics: Animals; Bronchi; Bronchiectasis; Bronchitis; Cricetinae; DNA; Elastin; Female; Lung; Lung Diseases; Male; Mesocricetus; Nitrates; Nitric Acid; Pulmonary Alveoli

Sputum samples from 34 patients with bronchiectasis were assessed subjectively and the results related to objective measurements of elastase activity and albumin content. The results suggest that the macroscopic appearance of the sample is related to the elastase content. 88.7% of the purulent samples but none of the mucoid samples showing elastase activity. The macroscopic appearance was also associated with changes in protein transudation into the secretions. The median sputum: serum albumin concentration ratio was 0.71 X 10(-2) (range 0.22-4.7) in the mucoid samples but was greater in purulent samples (p less than 0.005), with a median value of 1.52 X 10(-2) (range 0.55-12.72), suggesting that purulence in the stable state was associated with low grade pulmonary inflammation or epithelial damage or both. Abnormalities of air flow were found in 24 of the patients (70.6%) but there was a significantly higher ratio of residual volume to total lung capacity (p less than 0.025) in patients who regularly produced purulent sputum (mean (SD) RV/TLC 44.4% (9.0%] than in those with mucoid or mucopurulent secretions (38.0% (9.9%]. A similar difference was found between those who produced elastase positive secretions and those who produced elastase negative ones.

Topics: Adult; Aged; Bronchiectasis; Elastin; Female; Humans; Lung; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Respiratory Function Tests; Serum Albumin; Sputum; Suppuration