Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated. A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted. Patients (mean+/-SD age 64+/-11 yrs) included 17 never-smokers and eight ex-smokers (10.5+/-5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV(1) 41+/-12% pred, FEV(1)/FVC 49+/-14%, FVC 70+/-20% pred, RV 148+/-68% pred and RV/TLC 142+/-34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2+/-49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died. Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.
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PMID:Characterisation of severe obliterative bronchiolitis in rheumatoid arthritis. 1912 82

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome, including emphysema and airway disease. Phenotypes defined on the basis of chest computed tomography (CT) may decrease disease heterogeneity and aid in the identification of candidate genes for COPD subtypes. To identify these genes, we performed genome-wide linkage analysis in extended pedigrees from the Boston Early-Onset COPD Study, stratified by emphysema status (defined by chest CT scans) of the probands, followed by genetic association analysis of positional candidate genes. A region on chromosome 1p showed strong evidence of linkage to lung function traits in families of emphysema-predominant probands in the stratified analysis (LOD score = 2.99 in families of emphysema-predominant probands versus 1.98 in all families). Association analysis in 949 individuals from 127 early-onset COPD pedigrees revealed association for COPD-related traits with an intronic single-nucleotide polymorphism (SNP) in transforming growth factor-beta receptor-3 (TGFBR3) (P = 0.005). This SNP was significantly associated with COPD affection status comparing 389 cases from the National Emphysema Treatment Trial to 472 control smokers (P = 0.04), and with FEV(1) (P = 0.004) and CT emphysema (P = 0.05) in 3,117 subjects from the International COPD Genetics Network. Gene-level replication of association with lung function was seen in 427 patients with COPD from the Lung Health Study. In conclusion, stratified linkage analysis followed by association testing identified TGFBR3 (betaglycan) as a potential susceptibility gene for COPD. Published human microarray and murine linkage studies have also demonstrated the importance of TGFBR3 in emphysema and lung function, and our group and others have previously found association of COPD-related traits with TGFB1, a ligand for TGFBR3.
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PMID:Transforming growth factor-beta receptor-3 is associated with pulmonary emphysema. 1913 38

Data on sex differences in emphysema are limited to chronic obstructive pulmonary disease. We aimed to verify whether such differences also exist in smokers without airflow obstruction, weighting their influence on the relationship between emphysema and clinical features. We evaluated both clinical and multidetector computed tomography (MDCT) data of 1,011 heavy smokers recruited by a lung cancer screening project. MDCT scans were analysed with software allowing lobar quantification of emphysema features. For these measures, multiple regression models were applied to assess the effect of patients sex, after allowance for age, body mass index (BMI), smoking history, forced expiratory volume in 1 s (FEV(1)) and forced vital capacity. The final study cohort consisted of 957 smokers without airflow obstruction. Compared with males, females exhibited an emphysema phenotype less extensive in each pulmonary lobe, characterised by smaller emphysematous areas and less concentrated in the core of the lung. However, in females, the increase of emphysema with age was more pronounced and displayed a more significant relationship with FEV(1)% decline; conversely, in males there was a stronger association with the decrease in BMI. Males and females respond differently to the type and location of lung damage due to tobacco exposure. In smokers, sex influences the relationship between emphysema and clinical features.
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PMID:Sex differences in emphysema phenotype in smokers without airflow obstruction. 1916 51

The goal of this study was to seek indirect evidence that smoking is an aetiological factor in some patients with non-specific interstitial pneumonia (NSIP). Ten current and eight ex-smokers with NSIP were compared to controls including 137 current smokers with no known interstitial lung disease and 11 non-smokers with NSIP. Prevalence and extent of emphysema in 18 smokers with NSIP were compared with subjects meeting GOLD criteria for chronic obstructive pulmonary disease (COPD; group A; n = 34) and healthy smokers (normal FEV(1); group B; n = 103), respectively. Emphysema was present in 14/18 (77.8%) smokers with NSIP. Emphysema did not differ in prevalence between NSIP patients and group A controls (25/34, 73.5%), but was strikingly more prevalent in NSIP patients than in group B controls (18/103, 17.5%, P < 0.0005). On multiple logistic regression, the likelihood of emphysema increased when NSIP was present (OR = 18.8; 95% CI = 5.3-66.3; P < 0.0005) and with increasing age (OR = 1.04; 95% CI = 0.99-1.11; P = 0.08). Emphysema is as prevalent in smokers with NSIP as in smokers with COPD, and is strikingly more prevalent in these two groups than in healthy smoking controls. The association between NSIP and emphysema provides indirect support for a smoking pathogenesis hypothesis in some NSIP patients.
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PMID:Non-specific interstitial pneumonia in cigarette smokers: a CT study. 1921 21

Although previous authors have reported single data point, yearly changes in respiratory function have not been examined in combined pulmonary fibrosis and emphysema (CPFE). To quantify the annual changes in respiratory function of patients with CPFE and to examine the difference in survival between CPFE patients and patients with idiopathic pulmonary fibrosis without emphysema (IPF alone), 26 patients with CPFE and 33 IPF alone patients, whose respiratory function had been monitored for at least a year, were selected. The baseline of vital capacity percent predicted (VC% pred) in CPFE patients was greater than that in IPF-alone patients (86.6+/-24.0% vs. 72.8+/-19.4%, p=0.018). The annual decrease in VC% pred was significantly less in CPFE patients than in IPF-alone patients (-1.2+/-4.8% vs. -8.0+/-7.4%, p<0.001). Baseline ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC%) in CPFE patients was lower than that in IPF-alone patients (76.6+/-8.5% vs. 85.2+/-6.7%, p<0.001). In the CPFE group, FEV(1)/FVC% tended to decrease with time (-0.5+/-2.2% per year), but, in contrast, it increased in IPF-alone patients (+1.1+/-3.4% per year) (p=0.036). Baseline of diffusing capacity percent predicted (DLco% pred) was significantly lower in CPFE patients than in IPF-alone patients (45.3+/-15.0% vs. 60.7+/-19.8%, p=0.003). The annual decrease in DLco% pred was lower in CPFE patients than in IPF-alone patients (-3.7+/-7.9% vs. -10.7+/-8.8%, p=0.042). There was no significant difference in the survival duration between 26 CPFE and 33 IPF-alone patients according to Kaplan-Meier analysis. Ventilatory and gas-exchange deterioration during the course of IPF became mild when emphysema was coexistent.
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PMID:Coexistent emphysema delays the decrease of vital capacity in idiopathic pulmonary fibrosis. 1925 7

Informative value of clinical, electrocardiographic, and echocardiographic diagnostic criteria of compensated chronic pulmonary heart (CPH) in patients with chronic obstructive pulmonary disease (COPD) was considered. The study included 229 patients with COPD of which 105 (group 1) showed no signs of CPH, 71 (group 2) had compensated and 53 (group 3) uncompensated CPH. They were examined by the standard echoCG method using an Acuson-128 HR apparatus (USA) and 12-lead ECG during a 2 year-long follow-up period. Direct cardiac clinical and electrocardiographic signs of right ventricular eccentric hypertrophy were found to have high informative value (100%) but very low sensitivity (7-53%). Indirect diagnostic criteria of compensated CHP are such non-specific signs as age of COPD patients above 50 yr, duration of the disease over 8 yr and broncho-obstructive syndrome (episodes of low-productive cough, dyspnea under small physical load and at rest, X-ray signs of lung emphysema, substantial reduction of FEV and FEV/FVC ratio) in 73-94% of the patients were associated with compensated CPH. The most valuable (75.8-90.5%) cardiographic diagnostic criteria for compensated CPH were MPAP > 22 mmHg (at rest), LVEDD > 24 mm, LVEDS > 17 mm, RVWT = > 5 mm, RAEDD > 32 mm. Criterion LVEDD > 24 mm has the optimal ratio of sensitivity (94.4%), specificity (85.7%), and positive predictive value (86.6%). Comprehensive clinical assessment of COPD character and duration, patients' age, manifestation of broncho-obstructive syndrome and direct clinical signs suggesting involvement of the right half of the heart permits to predict CPH in patients with COPD with a probability of 75%. The definitive diagnosis is verified by echoCG or other instrumental methods.
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PMID:[Diagnosis of pulmonary heart in patients with chronic obstructive pulmonary disease]. 1934 4

Alpha-1-antitrypsin deficiency is associated with variable development of airflow obstruction and emphysema. Index patients have greater airflow obstruction than subjects detected by screening, but it is unclear if this reflects smoking differences and/or ascertainment bias, or is due to additional genetic factors. In this study 72 sibling pairs with alpha-1-antitrypsin deficiency were compared using lung function measurements and HRCT chest. Tag single nucleotide polymorphisms to cover all common variation in four genes involved in relevant inflammatory pathways (Tumour necrosis factor alpha, Transforming growth Factor beta, Surfactant protein B and Vitamin D binding protein) were genotyped using TaqMan technology and compared between pairs for their frequency and relationship to lung function. 63.5% of non-index siblings had airflow obstruction and 59.5% an FEV(1) < 80% predicted. Index siblings had lower FEV(1) and FEV(1)/FVC ratio, a higher incidence of emphysema (all P <or= 0.001) and lower gas transfer (P = 0.02). There was no correlation of FEV(1) between siblings but KCO was significantly correlated (r = 0.42, P = 0.002). Quantitative analyses against lung function showed that a polymorphism in Surfactant protein B was associated with FEV(1) (P = 0.002). This result was replicated in a non-sibling group (P = 0.01). Our results show that clinical differences in families with alpha-1-antitrypsin deficiency are not solely explained by smoking or ascertainment bias and may be due to variation within genes involved in inflammatory pathways.
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PMID:Phenotypic differences in alpha 1 antitrypsin-deficient sibling pairs may relate to genetic variation. 1935 49

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 microg bid, or placebo. COPD was defined as FEV(1) < or = 70% pred, FEV(1)/FVC < or = 60% and no reversibility to beta(2)-agonists and oral corticosteroids. The patients were followed for 2-4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15th percentile density (PD15) and the relative area of emphysema at a threshold of -910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV(1) was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was -1.12 g/L in the budesonide group and -1.81 g/L in the placebo group (p = 0.09); the annual increase in RA-910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV(1) between ICS (-54 mL) and placebo (-56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.
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PMID:The effect of inhaled corticosteroids on the development of emphysema in smokers assessed by annual computed tomography. 1937 23

Studies on pallid mice models of genetic emphysema have conventionally focused on morphological or biochemical evaluations. However, it is important to consider the functional aspects. We evaluated the exercise capacity and respiratory function in male pallid mice and male C57BL/6J mice at 3, 6, 12, and 15 months of age. The functional evaluations were conducted using a treadmill and a pulmonary function analysis device. The morphology of the lungs was analyzed on the basis of mean linear intercept (Lm) values. The body weights of the pallid mice at 12 and 15 months were significantly lower than those of the age-matched C57BL/6J mice. The pallid mice showed deterioration in exercise capacity from 6 months, as indicated by the trends in running distance. At 6, 12, and 15 months, the pallid mice showed significantly higher pulmonary compliance and significantly lower forced expiratory volume in 20 ms (FEV(20 ms))/vital capacity (VC) values in comparison with the corresponding values for the C57BL/6J mice. In the morphological analysis of the pallid mice, emphysema was detected from 12 months, and the mice showed a significantly larger Lm at 12 months. The exercise capacity and lung function in the pallid mice significantly deteriorated from 6 months, at which time no pathological changes in the lung were detected. The deterioration in the exercise capacity and pulmonary function preceded the microscopic morphological changes.
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PMID:Functional evaluation of pallid mice with genetic emphysema. 1938 Nov 31

Smoking is the main risk factor for COPD (chronic obstructive pulmonary disease) but genetic factors are of importance, since only a subset of smokers develops the disease. Sex differences have been suggested both in disease prevalence and response to environmental exposures. Furthermore, it has been shown that acquisition of 'addiction' to smoking is partly genetically mediated. Disease cases and smoking habits were identified in 44919 twins aged >40 years from the Swedish Twin Registry. Disease was defined as self-reported chronic bronchitis or emphysema, or recurrent cough with phlegm. The results showed that chronic bronchitis seems to be more prevalent among females, and that the heritability estimate for chronic bronchitis was a moderate 40% and only 14% of the genetic influences were shared by smoking. In addition, 392 twins have been invited to a clinical investigation to evaluate: (i) to what extent genetic factors contribute to individual differences (variation) in FEV(1) (forced expiratory volume in 1 s), vital capacity and DL(CO) (diffusion capacity), taking sex into consideration, and (ii) whether smoking behaviour and respiratory symptoms influence these estimates.
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PMID:Twins studies as a model for studies on the interaction between smoking and genetic factors in the development of chronic bronchitis. 1961


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