UNIPROT:Q99581 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:Q99581 (FEV)
3,296 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exacerbations of chronic obstructive pulmonary disease (COPD) cause morbidity, hospital admissions, and mortality, and strongly influence health-related quality of life. Some patients are prone to frequent exacerbations, which are associated with considerable physiologic deterioration and increased airway inflammation. About half of COPD exacerbations are caused or triggered primarily by bacterial and viral infections (colds, especially from rhinovirus), but air pollution can contribute to the beginning of an exacerbation. Type 1 exacerbations involve increased dyspnea, sputum volume, and sputum purulence; Type 2 exacerbations involve any two of the latter symptoms, and Type 3 exacerbations involve one of those symptoms combined with cough, wheeze, or symptoms of an upper respiratory tract infection. Exacerbations are more common than previously believed (2.5-3 exacerbations per year); many exacerbations are treated in the community and not associated with hospital admission. We found that about half of exacerbations were unreported by the patients, despite considerable encouragement to do so, and, instead, were only diagnosed from patients' diary cards. COPD patients are accustomed to frequent symptom changes, and this may explain their tendency to underreport exacerbations. COPD patients tend to be anxious and depressed about the disease and some might not seek treatment. At the beginning of an exacerbation physiologic changes such as decreases in peak flow and forced expiratory volume in the first second (FEV(1)) are usually small and therefore are not useful in predicting exacerbations, but larger decreases in peak flow are associated with dyspnea and the presence of symptomatic upper-respiratory viral infection. More pronounced physiologic changes during exacerbation are related to longer exacerbation recovery time. Dyspnea, common colds, sore throat, and cough increase significantly during prodrome, indicating that respiratory viruses are important exacerbation triggers. However, the prodrome is relatively short and not useful in predicting onset. As colds are associated with longer and more severe exacerbations, a COPD patient who develops a cold should be considered for early therapy. Physiologic recovery after an exacerbation is often incomplete, which decreases health-related quality of life and resistance to future exacerbations, so it is important to identify COPD patients who suffer frequent exacerbations and to convince them to take precautions to minimize the risk of colds and other exacerbation triggers. Exacerbation frequency may vary with the severity of the COPD. Exacerbation frequency may or may not increase with the severity of the COPD. As the COPD progresses, exacerbations tend to have more symptoms and take longer to recover from. Twenty-five to fifty percent of COPD patients suffer lower airway bacteria colonization, which is related to the severity of COPD and cigarette smoking and which begins a cycle of epithelial cell damage, impaired mucociliary clearance, mucus hypersecretion, increased submucosal vascular leakage, and inflammatory cell infiltration. Elevated sputum interleukin-8 levels are associated with higher bacterial load and faster FEV(1) decline; the bacteria increase airway inflammation in the stable patient, which may accelerate disease progression. A 2-week course of oral corticosteroids is as beneficial as an 8-week course, with fewer adverse effects, and might extend the time until the next exacerbation. Antibiotics have some efficacy in treating exacerbations. Exacerbation frequency increases with progressive airflow obstruction; so patients with chronic respiratory failure are particularly susceptible to exacerbation.
...
PMID:Exacerbations of chronic obstructive pulmonary disease. 1465 61

Study objectives were to evaluate the 1-hour decision point for discharge or admission for acute asthma; to compare this decision point to the admission recommendations of the Expert Panel Report 2 (EPR-2) guidelines; to develop a model for predicting need for admission in acute asthma. The design used was a prospective preinterventional and postinterventional comparison. The setting was a university hospital emergency department. Participants included 50 patients seeking care for acute asthma. Patients received standard therapy and were randomized to receive albuterol by nebulizer or metered-dose inhaler with spacer every 20 minutes up to 2 hours. Symptoms, physical examination, spirometry, pulsus paradoxus, medication use, and outcome were evaluated. Based on clinical judgment, the attending physician decided to admit or discharge after 1 hour of therapy. Outcome was compared to the EPR-2 guidelines. Post hoc statistical analyses examined predictors of the need for admission from which a prediction model was developed. Maximal accuracy of the admit versus discharge decision occurred at 1 hour of therapy. Using FEV(1) alone as an outcome predictor yielded suboptimal performance. FEV(1) at 1 hour plus ability to lie flat without dyspnea were the best indicators of response and outcome. A model predictive of the need for admission was developed. It performed better (P =.0054) than the admission algorithm of the EPR-2 guidelines. The decision to admit or discharge acute asthmatics from the ED can be made at 1 hour of therapy. No absolute value of peak flow or FEV(1) reliably predicts need for hospital admission. The EPR-2 guideline thresholds for admission are barely adequate as outcome predictors. A clinical model is proposed that may allow more accurate outcome prediction.
...
PMID:A prospective evaluation of the 1-hour decision point for admission versus discharge in acute asthma. 1503 63

Background: The objective of the study was to evaluate whether Hoover's sign-the paradoxical inspiratory movement of the lateral rib margin-may have clinical implications in patients with COPD. Methods: The study included two groups of male patients with stable COPD-30 with and 30 without Hoover's sign-who were matched for age and smoking habits. Spirometric values were assessed for both groups. Degree of dyspnea, measured for normal activities with the Medical Research Council (MRC) scale and for climbing two flights of stairs with the Borg scale, and utilization of health resources, including hospitalization, were compared. Results: Patients with Hoover's sign had a higher degree of dyspnea [MRC 2.2 (S.D.: 1.2) and 1.0 (0.8), p<0.0001; Borg 5.6 (2.4) and 3.1 (2.3), p=0.0001] and a higher number of hospitalizations [0.87 (1.0) and 0.27 (0.5), p=0.005] and emergency visits [2.5 (2.3) and 0.9 (2.3), p=0.01] than patient's without it. FEV(1) significantly correlated with dyspnea scales only in patients with Hoover's sign (MRC r=0.48; Borg r=0.49; p<0.05). Conclusions: Our study shows that Hoover's sign in COPD identifies a group of patients with a higher level of dyspnea and a higher use of health care resources, regardless of the degree of functional impairment. Consequently, establishing the presence of Hoover's sign would appear to be valuable in treating patients with COPD.
...
PMID:Clinical implications of Hoover's sign in chronic obstructive pulmonary disease. 1506 49

Chronic obstructive pulmonary disease (COPD) is defined by progressive, irreversible airflow limitation and an inflammatory response of the lungs, usually to cigarette smoke. However, COPD is a heterogeneous disease in terms of clinical, physiologic, and pathologic presentation. We aimed to evaluate whether airflow limitation, airway responsiveness, and airway inflammation are separate entities underlying the pathophysiology of COPD by using factor analysis. A total of 114 patients (99 males/15 females, age 62 +/- 8 years, 42 pack-years smoking, no inhaled or oral steroids > 6 months) with irreversible airflow limitation (postbronchodilator FEV(1) 63 +/- 9% predicted, FEV(1)/inspiratory vital capacity [IVC] 48 +/- 9%) and symptoms of chronic bronchitis or dyspnea were studied in a cross-sectional design. Postbronchodilator FEV(1) and FEV(1)/IVC, reversibility to inhaled beta(2)-agonists, diffusing capacity, provocative concentration of methacholine required to produce a 20% drop in FEV(1), total serum IgE, exhaled nitric oxide, and induced sputum cell counts (% eosinophils, % neutrophils) were collected. Factor analysis yielded 4 separate factors that accounted for 63.6% of the total variance. Factor 1 was comprised of FEV(1), FEV(1)/IVC, and residual volume/total lung capacity. Factor 2 included reversibility, IgE, provocative concentration of methacholine required to produce a 20% drop in FEV(1,) and diffusing capacity. Factor 3 contained exhaled nitric oxide and factor 4 included sputum % neutrophils and % eosinophils. We conclude that airflow limitation, airway inflammation, and features commonly associated with asthma are separate and largely independent factors in the pathophysiology of COPD.
...
PMID:Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease. 1591 69

Hypersensitivity pneumonitis, also called extrinsic allergic alveolitis, a type of diffuse parenchymal lung disease (DPLD), is an immunologically mediated pulmonary disease induced by inhalation of various antigens. As data on the frequency of hypersensitivity pneumonitis are lacking in Turkey, a retrospective analyses was performed in 43 patients with DPLD, followed up over seven years. The objective was to discover cases fulfilling the diagnostic criteria for hypersensitivity pneumonitis, to determine the frequency and/or the new characteristics of the disease, and to pick up clues for differentiating it from other DPLDs. The four subjects with hypersensitivity pneumonitis (9%) who lived in an urban area were studied in detail. The most common symptoms were dry cough and dyspnoea. According to the symptom duration, clinical features, radiological and pathological findings, three were diagnosed with chronic and one with subacute hypersensitivity pneumonitis. Patients with hypersensitivity pneumonitis and those with DPLD were compared by means of age, sex, smoking status, symptom duration, haematology, erythrocyte sedimentation rate, peripheral cell count, spirometric parameters, blood gases, and diffusion capacity. No statistically significant difference was detected in these parameters except for forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). In conclusion, patients with a history of antigen exposure, with mild symptoms such as dry cough and dyspnoea, and who have diffuse interstitial lung involvement on radiology should be carefully evaluated for hypersensitivity pneumonitis. Moreover, among other DPLDs, stable FEV(1) or FVC values may be the clues for establishing the diagnosis of hypersensitivity pneumonitis. However, further studies are needed in larger series of patients.
...
PMID:Clues for the differential diagnosis of hypersensitivity pneumonitis as an expectant variant of diffuse parenchymal lung disease. 1519 66

Tiotropium bromide (Spiriva) is a long-acting anticholinergic bronchodilator that maintains bronchodilation for at least 24 hours, allowing once-daily administration. The active moiety is the tiotropium cation (tiotropium); tiotropium bromide 22.5 micrograms is equivalent to 18 micrograms of tiotropium cation. Greater improvements in lung function from baseline (primary endpoint mean trough FEV(1)) were observed with inhaled tiotropium 18 micrograms once daily than with placebo in 6-month and 1-year randomized, double-blind trials in patients with COPD. Tiotropium improved lung function (trough FEV(1) response) more effectively than ipratropium bromide (ipratropium) 40 micrograms four times daily in 1-year clinical trials, and was at least as effective as salmeterol 50 micrograms 12-hourly in 6-month trials. Preliminary data suggest that tiotropium alone or in combination with once-daily formoterol has a greater bronchodilator effect than twice-daily formoterol in patients with COPD. Improvements in patients' perception of health-related quality of life (HR-QOL) or dyspnea were greater with tiotropium than with placebo or ipratropium, and were similar to those with salmeterol. Reductions in the frequency and severity of acute exacerbations and in the use of rescue medication were also greater with tiotropium than with ipratropium or placebo. There was no evidence of tachyphylaxis with tiotropium during 1-year clinical trials. Inhaled tiotropium was generally well tolerated in clinical trials. Apart from dry mouth, the type and incidence of adverse events with tiotropium were similar to those with ipratropium, salmeterol or placebo in patients with COPD. In conclusion, inhaled tiotropium 18 micrograms once daily improved lung function, dyspnea, and HR-QOL, and decreased the incidence of acute COPD exacerbations and the use of rescue medication relative to placebo or ipratropium in clinical trials in patients with COPD. Tiotropium was at least as effective as salmeterol in terms of bronchodilator efficacy and improvements in dyspnea or HR-QOL. With the exception of dry mouth, the tolerability profile of tiotropium was similar to that with placebo, ipratropium, or salmeterol. Consequently, inhaled tiotropium is likely to be a valuable option for first-line, long-term maintenance therapy in the management of bronchoconstriction in patients with symptomatic COPD. Tiotropium bromide has a quaternary ammonium structure and acts as an anticholinergic bronchodilator; the active moiety is the tiotropium cation (tiotropium). A 22.5 micrograms dose of tiotropium bromide provides 18 micrograms of tiotropium. Orally inhaled tiotropium bromide antagonizes the muscarinic M(1), M(2), and M(3) receptors located in airway smooth muscle, reversing vagally mediated bronchoconstriction. Receptor binding assays and in vitro tests indicate that tiotropium bromide is kinetically selective for M(1) and M(3) receptors over the M(2) receptor, unlike ipratropium bromide, which is nonselective. Animal and in vitro studies showed that tiotropium bromide was more potent ( approximate, equals 20-fold) than ipratropium bromide in displacing [(3)H]N-methylscopolamine (NMS) from muscarinic receptors, and had a more sustained protective effect (>70% inhibition) against NMS binding. Tiotropium bromide was a more potent inhibitor of bronchial contraction than atropine ( approximate, equals 23-fold), and had a slower onset and markedly longer duration of action than atropine or an equipotent dose of ipratropium bromide. Aerosol particle penetration is improved with tiotropium, without delaying mucus clearance from the lungs. Tiotropium 4.5-36 micrograms once daily for 4 weeks increased mean trough and average FEV(1) and FVC and mean PEFR values from baseline compared with placebo, with no evidence of tachyphylaxis. Improvements in trough FEV(1) from baseline with tiotropium 4.5-36 micrograms were not dose dependent. Based on a lack of dose response, the optimal once-daily tiotropium dosage is 18 micrograms. Steady-state trough FEV(1) values are achieved within 48 hours of commencing tiotrochodilation (for >/=24 hours) and an attenuation of the nocturnal decline in FEV(1) that were unaffected by timing of the daily tiotropium dose were seen in randomized, double-blind, placebo-controlled studies in patients with stable COPD. The drug improved static and dynamic lung hyperinflation (evidenced by reduced trapped air volume and increased tidal volume and end-of-exercise inspiratory capacity), and improved exertional dyspnea (during activities of daily living and exertion) and exercise tolerance compared with placebo in randomized, double-blind studies. In patients with stable COPD, improved sleep-related oxygen desaturation that was unaffected by the timing of the daily dose was seen with tiotropium but not with placebo. Clinically significant treatment-related disorders of conduction or rhythm, or changes in heart rate were not observed with tiotropium in this patient group. Mean maximal plasma concentrations (C(max)) were observed within 5 minutes of inhalation of a single dose of tiotropium 18 micrograms in patients with COPD. Plasma drug levels declined to minimum concentrations (C(min)) within 1 hour of treatment in healthy volunteers. Mean steady-state C(max) concentrations (16 ng/L) were achieved after 2-3 weeks of once-daily inhaled tiotropium 18 micrograms in elderly patients with COPD; tiotropium does not appear to accumulate once steady-state has been achieved.The estimated absolute bioavailability of tiotropium at steady state in healthy volunteers was approximately 20-25%, and approximately 72% of the drug is bound to plasma proteins. Excretion of tiotropium is predominantly renal (through active secretion by the kidneys), although in vitro studies suggest that cytochrome P450 (CYP) oxidation (possibly involving CYP2D6 and CYP3A4 enzymes) may have a minor role. In patients with COPD, renal excretion of the unchanged drug at 24 hours (Ae(24)) was approximately 7%. The mean plasma elimination half-life after single or multiple doses in healthy volunteers and elderly patients with COPD was approximately 5-6 days. The renal clearance and urinary excretion of tiotropium decrease with increasing age; however, these changes are not considered to be clinically significant. Because of altered steady-state C(max), C(min), area under the concentration-time curve, and Ae(24) values, caution is required with tiotropium administration in patients with moderate-to-severe renal impairment. The pharmacokinetics of tiotropium in patients with severe renal or hepatic impairment have not been studied. Tiotropium does not interact with drugs such as cimetidine or ranitidine, which are also eliminated by active renal secretion. Orally inhaled tiotropium bromide has been evaluated as a bronchodilator for the management of patients with COPD in randomized, double-blind 6-month and 1-year trials, and in several shorter studies. In clinical trials, COPD was diagnosed according to the American Thoracic Society guidelines. The bronchodilator effect was expressed as the trough FEV(1) response (the mean change in FEV(1) from baseline measured 1 hour prior to and immediately before a scheduled dose), and was the primary endpoint in all but two clinical trials. The bronchodilator effect with tiotropium 18 micrograms once daily was superior to that with placebo in several well designed trials in patients with COPD. Moreover, greater improvements in mean peak and average FEV(1) responses occurred with tiotropium but not with placebo. Mean trough, peak, and average FVC responses, and weekly mean morning and evening PEFR values were also improved to a greater extent with tiotropium than with placebo. Tiotropium demonstrated a greater bronchodilator effect than ipratropium bromide (hereafter referred to as ipratropium when used at approved dosages) 40 micrograms four times daily in two 1-year trials in patients with COPD. Mean peak and average FEV(1), mean trough FVC responses, and weekly mean morning and evening PEFR values were also increased to a greater extent with tiotropium than with ipratropium. In one of the two 6-month trials that compared the efficacy of tiotropium with that of inhaled salmeterol 50 micrograms twice daily, greater improvements from baseline in mean trough, peak, and average FEV(1) and FVC responses were seen with tiotropium than with salmeterol. Increases in weekly mean evening, but not morning, PEFR values were generally greater with tiotropium than salmeterol. In the second trial, improvement in the primary endpoint (mean trough FEV(1) response from baseline) with tiotropium or salmeterol was similar, although peak and average responses were superior with tiotropium. Preliminary results from a 6-week crossover study in patients with COPD suggested that tiotropium alone or in combination with once-daily formoterol improved mean trough and average FEV(1) and trough FVC values from baseline to a greater extent than twice-daily formoterol. More patients achieved a clinically important improvement (increase of >/=1 unit) in the transitional dyspnea index focal score (a measure of dyspnea-related impairment) with tiotropium than with placebo in the 1-year trials. Tiotropium was superior to ipratropium in 1-year trials, and was at least as effective as salmeterol in 6-month trials, in achieving a clinically important improvement in focal scores. Tiotropium recipients experienced fewer COPD exacerbations than placebo or ipratropium recipients and had fewer and shorter COPD-related hospitalizations compared with placebo recipients. Unlike salmeterol, tiotropium lengthened the time to onset of the first exacerbation and decreased the number of exacerbations compared with placebo in two 6-month trials. Similar proportions of tiotropium, salmeterol, and placebo recipients required COPD-related hospitalizations. (ABSTRACT TRUNCATED)
...
PMID:Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD. 1535 Jan 63

Asthma severity in relation to body mass index (BMI) has rarely been studied. The relation between BMI and asthma severity was studied by sex in 366 adults with asthma from the Epidemiological Study on the Genetics and Environment of Asthma, a case-control and family study on asthma. Factors related to asthma severity and BMI such as smoking, FEV(1), bronchial hyperresponsiveness, and dyspnea were taken into account. The influence of early menarche was studied to assess the potential role of hormonal factors. Clinical asthma severity in the last 12 months was assessed by a score (0-7) based on the frequency of asthma attacks, persisting symptoms between attacks, and hospitalization. Asthma severity, which was unrelated to sex, increased with BMI in women (p = 0.0001) but not in men (p = 0.3). In women, the association remained after adjustment for age, FEV(1), smoking habits, and BMI-adjusted dyspnea and taking into account familial dependence (p = 0.0001). The association between BMI and severity was stronger in women with early menarche than in women without early menarche (p interaction = 0.02). Findings support the hypothesis of hormonal factors involved in the severity of asthma.
...
PMID:Asthma severity is associated with body mass index and early menarche in women. 1555 34

Static lung hyperinflation has important clinical consequences in patients with chronic obstructive pulmonary disease. We analyzed the power of lung hyperinflation as measured by the inspiratory capacity-to-total lung capacity ratio (IC/TLC) to predict mortality in a cohort of 689 patients with chronic obstructive pulmonary disease (95% males; FEV(1), 1.17 L) with a mean follow-up of 34 months. We also compared the predictive value of IC/TLC with that of the BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index. Subjects who died (183; 27%) were older; had lower body mass index, FEV(1), and IC/TLC ratio; walked less in the 6-minute walking distance; and had more dyspnea, a higher BODE Index, and comorbidity (p < 0.001). On the basis of logistic regression analysis, IC/TLC was found to be a good and independent predictor of all-cause and respiratory mortality. On the basis of receiver operating characteristic Type II curves, IC/TLC compared favorably with FEV(1) and predicted mortality independently of the BODE Index. We conclude that IC/TLC is an independent risk factor for mortality in subjects with chronic obstructive pulmonary disease. We propose that this ratio be considered in the assessment of patients with chronic obstructive pulmonary disease.
...
PMID:Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. 1559 70

We studied the relationships among functional performance and three symptoms--dyspnea, fatigue, and sleep difficulty--in a sample of 100 people with chronic obstructive pulmonary disease (COPD). All participants had an FEV(1) 60% or less of the predicted level for age, sex, and height. Consistent with the Theory of Unpleasant Symptoms, dyspnea correlated with both fatigue and sleep difficulty. Dyspnea and fatigue both had moderate negative correlations with functional performance, while sleep difficulty had a small nonsignificant negative correlation with functional performance. After controlling for age and oxygen use, dyspnea was the only symptom to predict variance in functional performance significantly. Of the three symptoms studied, only dyspnea was related to both the other symptoms and to functional performance. Focusing on dyspnea may be the best way to improve both symptom experience and functional performance in people with COPD.
...
PMID:Relationship between symptoms and functional performance in COPD. 1562 10

We report the changes in forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow rate during caesarean section under spinal anaesthesia, as indirect indices of the ability to cough effectively. There were progressive falls in forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) from the onset of anaesthesia till the abdomen was open, with these results failing to return to pre-incision levels by the time the patient reached the recovery room. Although none of our patients complained of dyspnoea or difficulty in coughing such falls in PEFR and FEV(1) may lead to an inability to cough effectively or clear inhaled vomit especially in patients with previously impaired respiratory function.
...
PMID:Changes in pulmonary function tests during spinal anaesthesia for caesarean section. 1563 42

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>