Chest X-ray Stage Research Articles

HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis.

Human leukocyte antigen (HLA)-DQB1 is one of the intriguing candidate genes in sarcoidosis. We performed high resolution molecular HLA-DQB1 typing on two groups of white patients (British [UK] and Dutch [NL]) in order to investigate the relationship between 19 DQB1 alleles and disease severity and progression. A total of 803 individuals were studied (133 UK and 102 NL patients, and 354 UK and 214 NL control subjects). Disease severity data included extrapulmonary disease, chest X-ray stage, lung diffusing capacity for carbon monoxide, and FVC. Progression was evaluated on follow-up chest radiographs (2 and 4 yr). The results showed DQB1*0201 to be strongly protective against severe sarcoidosis in both populations; in other words, it localized to Stage I at all time points (P < 0.0001, P(corrected) (P(c)) = 0.002), whereas another DQB1 allele, *0602, tended to have opposite effects. Further, a clear association was found between the *0201 allele and Löfgren's syndrome (P < 0.0001, P(c) = 0.001). More importantly, carriage of this allele reduced the risk of disease progression. In contrast, the other common split of DQB1*02, *0202, did not affect disease severity but was mildly protective against sarcoidosis in the UK population (P = 0.02, p(c) not significant). In conclusion, this study shows that DQB1*0201 is a strong marker for mild sarcoidosis. Additional mapping across the DQB1*0201-DRB1*0301 haplotype, including specific alleles at genes such as DRB3, tumor necrosis factor, lymphotoxin-alpha, I-kappa-B-like protein, and B-associated transcript 1, is necessary for a final localization of the protective effect on this haplotype.

Sarcoidosis Patients Have Bronchial Hyperreactivity and Signs of Mast Cell Activation in Their Bronchoalveolar Lavage

An increased (p < 0.001) frequency of bronchial hyperreactivity (BHR) was found in sarcoidosis patients as compared with healthy volunteers. The patients had more mast cells (p < 0.001) and tryptase (p < 0.001) in their bronchoalveolar lavage fluid, but there were no differences between BHR-positive and BHR-negative patients. Furthermore, the bronchoalveolar lavage fluid concentrations of macrophages, lymphocytes, and of the soluble components albumin, fibronectin, and vitronectin were also elevated in the sarcoidosis patients, indicating an ongoing inflammation in the airways and/or in the interstitium. We observed no significant differences in the parameters when the sarcoidosis patients were subdivided into BHR, clinical activity, or chest X-ray stages. Our findings may indicate a multifactorial background to the hyperreactivity.

Exercise test in patients with sarcoidosis. The importance of repolarization disturbances.

The study population comprises 28 patients with sarcoidosis who all had repolarization disturbances in their exercise ECGs. None of the patients had hypertension or known cardiovascular disease, and all but two were non-smokers. The mean age was 45 years. Exercise test with beta-adrenergic blockade was performed within one month of the first examination. Persisting abnormal ST-T changes in exercise ECGs after beta-blockade were seen in 12 (43%) patients. No significant relationship was found between persisting ST-T changes and age, sex, chest X-ray stage, lung function or working capacity. In an earlier study, we found ST-T abnormalities in exercise ECG in 56 of 127 individuals (44%) in a consecutive 5-year study of patients with newly detected sarcoidosis. From this and the present report we postulate that, in our region, as much as 20% of the patients with newly detected sarcoidosis might have organic myocardial disease, possibly of sarcoid origin, as shown by repolarization disturbances in exercise ECG. If ECG abnormalities in the ST-T region are present in patients with sarcoidosis, exercise ECG with beta-blockade is a simple way of establishing suspicion of organic myocardial lesions. If exercise ECG abnormalities in the ST-T region persist after beta-blockade, careful clinical follow-up is recommended, and, in some patients early steroid therapy should be considered.

Echocardiographic evaluation of patients with systemic sarcoidosis

Echocardiographic evaluation of 42 patients with sarcoidosis disclosed 13 patients (group A) with abnormalities compatible with sarcoid heart involvement such as thickening or thinning of the septum (eight patients), pericardial effusion (four patients), and increased end-diastolic dimension of the left ventricle with decreased systolic function (three patients). The remaining 29 patients (group B) were diagnosed as having normal echocardiograms. The clinical data reavealed no statistically significant difference between the groups regarding age, sex, chest x-ray stage, activity, and previous heart disease. Group A patients had older clinical onset of the disease (52 vs 83 months; p < 0.05) and higher incidence of ECG abnormalities than group B patients. There were no statistically significant differences between the groups regarding two-dimensional echocardiographic internal dimensions of both ventricular chambers. The radionuclear right ventricular ejection fraction was low in both groups and the left ventricular ejection fraction was depressed in group A patients ( p < 0.01). As observed in pathologic studies, the septum is a target structure which can be characterized echocardiographically. Screening suspected sarcoid heart disease involvement is important to characterize patients with a relatively high risk of clinical cardlac abnormalities such as complete atrioventricular block, ventricular arrhythmias, congestive heart failure, and sudden death.