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1.
Early origins of chronic obstructive lung diseases across the life course.
Duijts, L, Reiss, IK, Brusselle, G, de Jongste, JC
European journal of epidemiology. 2014;(12):871-85
Abstract
Chronic obstructive lung diseases, like asthma and chronic obstructive pulmonary disease, have high prevalences and are a major public health concern. Chronic obstructive lung diseases have at least part of their origins in early life. Exposure to an adverse environment during critical periods in early life might lead to permanent developmental adaptations which results in impaired lung growth with smaller airways and lower lung volume, altered immunological responses and related inflammation, and subsequently to increased risks of chronic obstructive lung diseases throughout the life course. Various pathways leading from early life factors to respiratory health outcomes in later life have been studied, including fetal and early infant growth patterns, preterm birth, maternal obesity, diet and smoking, children's diet, allergen exposure and respiratory tract infections, and genetic susceptibility. Data on potential adverse factors in the embryonic and preconception period and respiratory health outcomes are scarce. Also, the underlying mechanisms how specific adverse exposures in the fetal and early postnatal period lead to chronic obstructive lung diseases in later life are not yet fully understood. Current studies suggest that interactions between early environmental exposures and genetic factors such as changes in DNA-methylation and RNA expression patterns may explain the early development of chronic obstructive lung diseases. New well-designed epidemiological studies are needed to identify specific critical periods and to elucidate the mechanisms underlying the development of chronic obstructive lung disease throughout the life course.
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2.
The potential role of natural agents in treatment of airway inflammation.
Sharafkhaneh, A, Velamuri, S, Badmaev, V, Lan, C, Hanania, N
Therapeutic advances in respiratory disease. 2007;(2):105-20
Abstract
Obstructive airway diseases including asthma, chronic obstructive pulmonary disease and cystic fibrosis present with dyspnea and variety of other symptoms. Physiologically, they are characterized by maximal expiratory flow limitation and pathologically, by inflammation of the airways and the lung parenchyma. Inflammation plays a major role in the gradual worsening of the lung function resulting in worsening symptoms. For many years, scientists focused their efforts in identifying various pathways involved in the chronic inflammation present in these diseases. Further, studies are underway to identify various molecular targets in these pathways for the purpose of developing novel therapeutic agents. Natural agents have been used for thousands of years in various cultures for the treatment of several medical conditions and have mostly proven to be safe. Recent in vivo and in vitro studies show potential anti-inflammatory role for some of the existing natural agents. This review provides an overview of the literature related to the anti-inflammatory effects of some of the natural agents which have potential value in the treatment of inflammatory lung diseases.
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3.
A benefit-risk assessment of inhaled long-acting beta2-agonists in the management of obstructive pulmonary disease.
Sovani, MP, Whale, CI, Tattersfield, AE
Drug safety. 2004;(10):689-715
Abstract
The two inhaled long-acting beta2-adrenoceptor agonists, salmeterol and formoterol, have been studied extensively since their introduction in the early 1990s. In this review we consider the evidence for their efficacy and safety in adults with asthma and chronic obstructive pulmonary disease (COPD), by reviewing long-term prospective studies in which these drugs have been compared with placebo or an alternative bronchodilator. We have also assessed safety, including data from postmarketing surveillance studies and case-control studies using large databases. In patients with asthma, salmeterol and formoterol increase lung function, reduce asthmatic symptoms and improve quality of life when compared with placebo. Both drugs protect against exercise-induced asthma, although some tolerance develops with regular use. Tolerance to the bronchodilator effects of formoterol has also been seen, although this is small and most of the beneficial effects are maintained long-term. Both drugs have been shown to reduce asthma exacerbations but only in studies in which most patients were taking an inhaled corticosteroid. Adding a long-acting beta2-agonist provided better control than increasing the dose of inhaled corticosteroid in several studies. Long-acting beta2-agonists also provide better asthma control than use of regular short-acting beta2-agonists and theophylline. Their relative efficacy compared with leukotriene antagonists is uncertain as yet. Formoterol appears to be at least as safe and effective as a short-acting beta2-agonist when used on an 'as required' basis. In patients with COPD, both salmeterol and formoterol offer improved lung function and reduced COPD symptoms compared with placebo, and quality of life has been improved in some studies. Some tolerance to the bronchodilating effect of salmeterol was seen in one study. Most studies have not found a significant reduction in exacerbations in COPD. Both drugs have provided greater benefit than ipratropium bromide or theophylline; there are limited data on tiotropium bromide. The long-acting beta2-agonists cause predictable adverse effects including headache, tremor, palpitations, muscle cramps and a fall in serum potassium concentration. Salmeterol can also cause paradoxical bronchospasm. There is some evidence that serious adverse events including dysrhythmias and life-threatening asthma episodes can occur; however, the incidence of such events is very low but may be increased in patients not taking an inhaled corticosteroid. Salmeterol 50 microg twice daily and formoterol 12 microg twice daily are effective and safe in treating patients with asthma and COPD. Higher doses cause more adverse effects, although serious adverse events are rare.
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4.
Best evidence topic report. Intravenous magnesium in chronic obstructive pulmonary disease.
Jenner, R, Body, R
Emergency medicine journal : EMJ. 2004;(2):203
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Abstract
A short cut review was carried out to establish whether the addition of intravenous magnesium to standard treatments improved outcome in patients with exacerbations of COPD. Altogether 465 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.
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5.
Nutrition in chronic critical illness.
Pingleton, SK
Clinics in chest medicine. 2001;(1):149-63
Abstract
Nutritional management of patients with respiratory failure can be a model of nutritional management in chronically critically ill patients. This model requires recognition of the differing metabolic states of starvation and hypermetabolism. Starvation can result in malnutrition, with adverse effect on respiratory muscle strength, ventilatory drive, and immune defense mechanisms. General nutritional goals include preservation of lean body mass by providing adequate energy and positive nitrogen balance. General nutritional prescriptions for both states include a substrate mix of 20% protein, 60% to 70% carbohydrates, and 20% to 30% fat. Positive nitrogen balance is difficult to attain in hypermetabolic patients and energy requirements are increased compared with starved patients. Enteral nutrition should be the mode of initial nutrient delivery unless the gastrointestinal tract is nonfunctional. Monitoring of nutritional support is essential. Complications of nutritional support are multiple. Nutritional hypercapnia is an important complication in a chronically critically ill patient. Outcomes of selected long-term acute patients are poor, with only 8% of patients fully functional 1 year after discharge. Appropriate nutritional therapy is one aspect of management of these patients that has the possibility of optimizing function and survival.
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6.
Exercise in chronic pulmonary disease: aerobic exercise prescription.
Cooper, CB
Medicine and science in sports and exercise. 2001;(7 Suppl):S671-9
Abstract
Endurance exercise training (EXT) is singly the most important aspect of rehabilitation for patients with chronic pulmonary disease. When effective, this modality of physical reconditioning leads to improved functional exercise capacity and reduced breathlessness. Early implementation is desirable to obtain more meaningful responses (e.g., when FEV1 falls below 50% of the predicted value in patients with chronic obstructive disease). Preparation for effective EXT requires optimization of respiratory system mechanics (e.g., using bronchodilator therapy), prevention of gas exchange failure (i.e., using supplemental oxygen), nutritional guidance, and psychological support (e.g., to overcome stigmata of disability, fear, and inclination to panic). EXT should be applied using a rigorous, scientifically based aerobic exercise prescription (AXRx) that recognizes basic principles of the human response to exercise prescription while considering individual pathophysiological limitations and identifying safety thresholds for exercise participation. The mode of aerobic exercise should use large muscle groups of the legs (e.g., treadmill or cycle ergometer). The recommended duration is an accumulation of 30 min of exercise per session at the target intensity, achieved by continuous or interval training. EXT should be supervised with a recommended frequency of at least three times per week for 6--8 wk. Target exercise intensity can be monitored by oxygen uptake, work rate, heart rate, or perceived exertion. Target intensity can be determined initially on the basis of 40% of a reference value for maximum oxygen uptake and linked to other variables through predictable interrelationships. All aspects of the AXRx must be reviewed with regard to progression during training. Pulmonary rehabilitation must recognize the importance of achieving clinically meaningful responses (e.g., increased 6-min walking distance of 54 m) as well as the need for maintenance exercise program to sustain the benefits.
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7.
Peripheral muscle dysfunction in chronic obstructive pulmonary disease.
Maltais, F, LeBlanc, P, Jobin, J, Casaburi, R
Clinics in chest medicine. 2000;(4):665-77
Abstract
Peripheral muscle dysfunction is a common systemic complication of moderate to severe COPD and may contribute to disability, handicap, and premature mortality. In contrast to the lung impairment, which is largely irreversible, peripheral muscle dysfunction is potentially remediable with exercise training, nutritional intervention, oxygen, and anabolic drugs. Therapeutic success is often incomplete, however, and a better understanding of the mechanisms involved in the development of peripheral muscle dysfunction in COPD is needed to help develop innovative and more effective therapeutic strategies.
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8.
Nonantimicrobial aspects of therapy.
Barnes, PJ
Seminars in respiratory infections. 2000;(1):52-8
Abstract
Current therapy for chronic obstructive pulmonary disease is symptomatic, and no treatments prevent the progression of the disease. Stopping smoking is the only effective approach, and this may be facilitated by nicotine replacement and bupropion. Treatment with short- and long-acting inhaled beta2-agonists and anticholinergics are the mainstay of therapy. Inhaled corticosteroids have no impact on disease progression, and the small reduction in exacerbations may not justify the potential systemic side effects. Supplementary oxygen therapy is indicated for acute exacerbations and chronic hypoxia. Other treatments, including mucolytics, vaccines, and respiratory stimulants are of little value. Nonpharmacological measures that are useful include pulmonary rehabilitation, exercise, good nutrition, and, in selected cases, surgery. Several new classes of drug are now in development, including mediator antagonists (leukotriene B4, interleukin-8 antagonists, and anti-oxidants) and nonsteroid anti-inflammatory drugs, of which phosphodiesterase-4 inhibitors look the most promising. There is a pressing need for a better understanding of the underlying disease process to develop more logical therapies.
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9.
Budesonide inhalation suspension: a review of its use in infants, children and adults with inflammatory respiratory disorders.
Hvizdos, KM, Jarvis, B
Drugs. 2000;(5):1141-78
Abstract
Budesonide, a topically active corticosteroid, has a broad spectrum of clinically significant local anti-inflammatory effects in patients with inflammatory lung diseases including persistent asthma. In infants and young children with persistent asthma, day- and night-time symptom scores, and the number of days in which beta2-agonist bronchodilators were required, were significantly lower during randomised, double-blind treatment with budesonide inhalation suspension 0.5 to 2 mg/day than placebo in 3 multicentre trials. Significantly fewer children discontinued therapy with budesonide inhalation suspension than with placebo because of worsening asthma symptoms in a study that included children who were receiving inhaled corticosteroids at baseline. Recent evidence indicates that budesonide inhalation suspension is significantly more effective than nebulised sodium cromoglycate in improving control of asthma in young children with persistent asthma. At a dosage of 2 mg/day, budesonide inhalation suspension significantly reduced the number of asthma exacerbations and requirements for systemic corticosteroids in preschool children with severe persistent asthma. In children with acute asthma or wheezing, the preparation was as effective as, or more effective than oral prednisolone in improving symptoms. In children with croup, single 2 or 4mg dosages of budesonide inhalation suspension were significantly more effective than placebo and as effective as oral dexamethasone 0.6 mg/kg or nebulised L-epinephrine (adrenaline) 4mg in alleviating croup symptoms and preventing or reducing the duration of hospitalisation. Early initiation of therapy with budesonide inhalation suspension 1 mg/day appears to reduce the need for mechanical ventilation and decrease overall corticosteroid usage in preterm very low birthweight infants at risk for chronic lung disease. In adults with persistent asthma, budesonide inhalation suspension < or =8 mg/day has been compared with inhaled budesonide 1.6 mg/day and fluticasone propionate 2 mg/day administered by metered dose inhaler. Greater improvements in asthma control occurred in patients during treatment with budesonide inhalation suspension than with budesonide via metered dose inhaler, whereas fluticasone propionate produced greater increases in morning peak expiratory flow rates than nebulised budesonide. Several small studies suggest that the preparation has an oral corticosteroid-sparing effect in adults with persistent asthma and that it may be as effective as oral corticosteroids during acute exacerbations of asthma or chronic obstructive pulmonary disease. The frequency of adverse events was similar in children receiving budesonide inhalation suspension 0.25 to 2 mg/day or placebo in 12-week studies. During treatment with budesonide inhalation suspension 0.5 to 1 mg/day in 3 nonblind 52-week studies, growth velocity in children was generally unaffected; however, a small but statistically significant decrease in growth velocity was detected in children who were not using inhaled corticosteroids prior to the introduction of budesonide inhalation suspension. Hypothalamic-pituitary-adrenal axis function was not affected by short (12 weeks) or long (52 weeks) term treatment with nebulised budesonide. In conclusion, budesonide inhalation suspension is the most widely available nebulised corticosteroid, and in the US is the only inhaled corticosteroid indicated in children aged > or =1 year with persistent asthma. The preparation is suitable for use in infants, children and adults with persistent asthma and in infants and children with croup.
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10.
The adolescent with respiratory disease.
Helms, P
Journal of the Royal College of Physicians of London. 2000;(2):134-7