This is partly because baseline HDAC activity is lower, but it is possible that theophylline interferes with signal transduction pathway(s) activated by oxidative stress. [2018]. The aim of this multi-centre, double blind, randomised, controlled trial (DBRCT) is to assess the effect of low dose theophylline, singly and in combination with low dose oral prednisone, on COPD (Chronic Obstructive Pulmonary Disease) exacerbations, quality of life and secondary clinical outcomes compared with usual therapy and placebo over 48 weeks of treatment. [2004, amended 2018], 1.1.12 [2004], 1.2.139 For most people with stable severe COPD regular hospital review is not necessary, but there should be locally agreed mechanisms to allow rapid access to hospital assessment when needed. 1.1.13 If the person is a current smoker, their spirometry results are normal and they have no symptoms or signs of respiratory disease: offer smoking cessation advice and treatment, and referral to specialist stop smoking services (see the NICE guideline on stop smoking interventions and services), warn them that they are at higher risk of lung disease, advise them to return if they develop respiratory symptoms, be aware that the presence of emphysema on a CT scan is an independent risk factor for lung cancer. [2004], 1.3.7 Include people's preferences about treatment at home or in hospital in decision-making. [2004], 1.2.114 Assess people who are using long-term oxygen therapy and who are planning air travel in line with the BTS recommendations[7]. 5. Institute for Health and Clinical Excellence (NICE) COPD 2004 guidelines recommend: ∗ COPD patients who smoke should... Read Summary. 2.1.1 Severity of COPD depends upon more than just the severity of airflow . An exacerbation is a sustained worsening of the patient's symptoms from their usual stable state which is beyond normal day-to-day variations, and is acute in onset. [2004], 1.3.38 Use pulse oximetry to monitor the recovery of people with non-hypercapnic, non-acidotic respiratory failure. Do not offer ambulatory oxygen to manage breathlessness in people with COPD who have mild or no hypoxaemia at rest. To find out why the committee made the 2018 recommendations on self-management and telehealth monitoring and how they might affect practice, see rationale and impact. [2004], 1.2.66 When theophylline was used as a bronchodilator at doses that give plasma concentrations of 10 to 20 mg/L, side effects due to PDE inhibition and adenosine antagonism were relatively common and often led to discontinuation of therapy. It is still widely prescribed worldwide, because it is inexpensive. [2004, amended 2018], 1.3.4 Hospital-at-home and assisted-discharge schemes are safe and effective and should be used as an alternative way of caring for people with exacerbations of COPD who would otherwise need to be admitted or stay in hospital. [2018]. Loppow D, Schleiss MB, Kanniess F, Taube C, Jörres RA, Magnussen H. In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation. Adenosine antagonism is likely to account for some of the serious side effects of theophylline, such as seizures and cardiac arrhythmias through blockade of A1 receptors. 1.2.21 In most cases bronchodilator therapy is best administered using a hand-held inhaler (including a spacer if appropriate). Before starting prophylactic antibiotic therapy in a person with COPD, think about whether respiratory specialist input is needed. [2004], 1.2.116 Warn people with bullous disease that they are at a theoretically increased risk of a pneumothorax during air travel. Decreased HDAC activity also results in increased NF-κB–mediated inflammatory gene expression without affecting NF-κB DNA binding (43). There is a marked reduction in HDAC activity in COPD alveolar macrophages, and it is restored to above normal by low concentrations of theophylline (49). However, people with significant cognitive impairment may be unable to use any form of inhaler device. These effects are generally seen only at high concentrations of theophylline that are above the therapeutic range, and they are, therefore, unlikely to contribute to the antiinflammatory actions of theophylline. 1.2.126 1.2.30 Do not continue nebulised therapy without assessing and confirming that 1 or more of the following occurs: an increase in the ability to undertake activities of daily living, 1.2.31 Use a nebuliser system that is known to be efficient[3]. Theophylline works by relaxing the smooth muscles of the airways while relieving inflammation and a… What is particularly attractive about this approach is that theophylline becomes more effective as oxidative stress increases, making it perfectly adaptable to treating all stages of COPD without having to change the dose. 1.1.14 Manufacturer makes no recommendation. Selection should depend on the resources available and absence of factors associated with a worse prognosis (for example, acidosis). The purpose of the assessment is to assess the extent of desaturation, the improvement in exercise capacity with supplemental oxygen, and the oxygen flow rate needed to correct desaturation. Do not offer short-burst oxygen therapy to manage breathlessness in people with COPD who have mild or no hypoxaemia at rest. NICE guideline [NG115] Consider whether people have anxiety or depression, particularly if they: have been seen at or admitted to a hospital with an exacerbation of COPD. [2004]. HDAC2 in COPD lungs shows excessive nitration and this is associated with reduced HDAC activity. Zhang Z-Y, Kaminsky LS. Related agents caffeine and theobromine were used in the 1930s as bronchodilators, and theophylline developed an established … Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Do not offer long-term oxygen therapy to treat isolated nocturnal hypoxaemia caused by COPD. [2004], 1.1.3 One of the primary symptoms of COPD is breathlessness. To find out why the committee made the 2019 recommendation on duration of oral corticosteroid use and how it might affect practice, see rationale and impact. [2018], 1.3.22 Only use intravenous theophylline as an adjunct to exacerbation management if there is an inadequate response to nebulised bronchodilators. 2,14 By contrast, an inhaled corticosteroid had little effect. [2018]. Available at URL. 1.3.8 Both nebulisers and hand-held inhalers can be used to administer inhaled therapy during exacerbations of COPD. When theophylline was introduced into asthma therapy, it was used as a bronchodilator, and early dose–response studies showed an increasing acute bronchodilator response above plasma concentrations of 10 mg/L (55 μM). The bronchodilator effect of theophylline in human airways is reduced by charybdotoxin, which selectively inhibits large-conductance Ca2+-activated K+ channels (maxi-K channels), suggesting that theophylline opens these maxi-K channels via an increase in cAMP (11). [2004], 1.3.26 Measure oxygen saturation in people with an exacerbation if there are no facilities to measure arterial blood gases. after 3 months, conduct a clinical review to establish whether or not LAMA+LABA+ICS has improved their symptoms: if symptoms have not improved, stop LAMA+LABA+ICS and switch back to LAMA+LABA, if symptoms have improved, continue with LAMA+LABA+ICS. [2004, amended 2018], 1.2.69 Prescribe ambulatory oxygen to people who are already on long-term oxygen therapy, who wish to continue oxygen therapy outside the home, and who are prepared to use it. [2004], 1.1.29 Consider spirometry in people with chronic bronchitis. COPD care should be delivered by a multidisciplinary team. Before starting LAMA+LABA+ICS, conduct a clinical review to ensure that: the person's non-pharmacological COPD management is optimised and they have used or been offered treatment for tobacco dependence if they smoke, acute episodes of worsening symptoms are caused by COPD exacerbations and not by another physical or mental health condition, the person's day-to-day symptoms that are adversely impacting their quality of life are caused by COPD and not by another physical or mental health condition. It can also be given intravenously (into a vein) for treatment for severe asthma attacks or COPD exacerbations. Base the choice of drugs and inhalers on: the person's preferences and ability to use the inhalers, the drugs' potential to reduce exacerbations, their cost.Minimise the number of inhalers and the number of different types of inhaler used by each person as far as possible. Repeat arterial blood gas measurements regularly, according to the response to treatment. [2004, amended 2018]. Histone deacetylases: unique players in shaping the epigenetic histone code. 1.2.75 Suspect a diagnosis of cor pulmonale for people with: a loud pulmonary second heart sound. A post bronchodilator ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) of less than 0.7 on spirometry confirms persistent airflow obstruction. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits IL-1β-induced histone H4 acetylation on lysines 8 and 12. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. Some people with advanced COPD may need long-term oral corticosteroids when these cannot be withdrawn following an exacerbation. Be alert for anxiety and depression in people with COPD. Theophylline: new perspectives for an old drug. This is because corticosteroid side effects are largely mediated by gene induction by corticosteroids, whereas antiinflammatory effects are mediated via HDAC. [2004], 1.3.20 [2018], 1.2.111 Regularly ask people with COPD about their ability to undertake activities of daily living and how breathless these activities make them. However, the most common side effects of theophylline are nausea, gastrointestinal symptoms, and headaches, which may be due to inhibition of certain PDEs (e.g., PDE4 in the vomiting center) (58). [2010], 1.1.8 All healthcare professionals who care for people with COPD should have access to spirometry and be competent in interpreting the results. [2004], 1.2.118 There are significant differences in the response of people with COPD and asthma to education programmes. [2004], 1.2.72 When choosing which equipment to prescribe, take account of the hours of ambulatory oxygen use and oxygen flow rate needed. 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