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], 1.3.16 The most common side effects are headache, nausea and vomiting, abdominal discomfort, and restlessness. Offer pneumococcal vaccination and an annual flu vaccination to all people with COPD, as recommended by the Chief Medical Officer. It is widely accepted that cigarette smoking is the key noxious stimulus leading to the development of COPD. Side effects of methylxanthines are common and potentially serious. [2004], 1.2.33 If nebuliser therapy is prescribed, provide the person with equipment, servicing, and ongoing advice and support. [2004], 1.2.140 When people with very severe COPD are reviewed in primary care they should be seen at least twice per year, and specific attention should be paid to the issues listed in table 6. Inhibition of NF-κB appears to be due to a protective effect against the degradation of the inhibitory protein IκB-α, so that nuclear translocation of activated NF-κB is prevented (29). [2004], 1.3.43 People who have had an episode of respiratory failure should have satisfactory oximetry or arterial blood gas results before discharge. A formal activities of daily living assessment may be helpful when there is still doubt. The findings from the TWICS (Theophylline With Inhaled CorticoSteroids) trial do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for prevention of COPD exacerbations, UK … Introduction. Acetylation of core histones is associated with activation and transcription of inflammatory genes and is regulated by coactivator molecules that have intrinsic histone acetyltransferase activity (36). Rennard SI. Severity grading has been recently updated (NICE CG101 2010) to bring into line with other international guidelines. The NICE guideline on COPD [ NICE, 2019a ] recommends that where combination therapy with long-acting bronchodilators and ICS is being considered, clinicians should be aware of, and discuss with the person, the risk of adverse effects including an increased … [4] At the time of publication (July 2019), azithromycin did not have a UK marketing authorisation for this indication. Hansel TT, Tennant RC, Tan AJ, Higgins LA, Neighbour H, Erin EM, Barnes PJ. Consider whether people have anxiety or depression, particularly if they: have been seen at or admitted to a hospital with an exacerbation of COPD. 1.2.26 Advise people to use a spacer with a metered-dose inhaler in the following way: administer the drug by single actuations of the metered-dose inhaler into the spacer, inhaling after each actuation, there should be minimal delay between inhaler actuation and inhalation, normal tidal breathing can be used as it is as effective as single breaths, repeat if a second dose is required. [2004], 1.2.72 When choosing which equipment to prescribe, take account of the hours of ambulatory oxygen use and oxygen flow rate needed. Introduction. [2019]. Clinicians should be aware that pulse oximetry gives no information about the PaCO2 or pH. There may also be novel structures that mimic the effect of theophylline that could be discovered by high-throughput screening, using HDAC activation as a read-out. The downregulation of Bcl-2 expression is necessary for theophylline-induced apoptosis of eosinophil. Theophylline is thought to potentially increase the sensitivity of inhaled corticosteroids in people with COPD by increasing the activity of HDAC2, which regulates the acetylation of core histones associated with the pro-inflammatory genes that drive chronic airway inflammation. Di Stefano A, Caramori G, Oates T, Capelli A, Lusuardi M, Gnemmi I, Ioli F, Chung KF, Donner CF, Barnes PJ. It does not appear to be of value in treatment of acute exacerbations of COPD, however (8). [2004], 1.2.65 Oxygen concentrators should be used to provide the fixed supply at home for long-term oxygen therapy. It is ironic that many of the drugs used to treat COPD have been known since antiquity, yet we are still struggling to understand their basic mechanisms and how to use them. 1.2.80 Do not offer short-burst oxygen therapy to manage breathlessness in people with COPD who have mild or no hypoxaemia at rest. Role of potassium channels in bronchodilator responses in human airways. At high concentrations, convulsions, cardiac arrhythmias, and death may occur. [2004], 1.2.105 Pay attention to changes in weight in older people, particularly if the change is more than 3 kg. Theophylline prevents the translocation of the proinflammatory transcription factor nuclear factor (NF)-κB into the nucleus, thus potentially reducing the expression of inflammatory genes in asthma and COPD (28). This effect of theophylline is completely reversed by trichostatin A, a nonselective inhibitor of HDACs, thereby confirming that the enhancement of corticosteroid responsiveness by theophylline is mediated via HDAC. Caramori G, Romagnoli M, Casolari P, Bellettato C, Casoni G, Boschetto P, Chung KF, Barnes PJ, Adcock IM, Ciaccia A. Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ. Give people (particularly people discharged from hospital) clear instructions on why, when and how to stop their corticosteroid treatment. Theophylline is a bronchodilator that is not commonly used for COPD in the U.S. since most people can use inhaled bronchodilators. Treatment is complicated by … 1.2.120 Ensure the information provided is: relevant to the stage of the person's condition. It is still widely prescribed worldwide, … [2004], 1.2.136 If time permits, optimise the medical management of people with COPD before surgery. [2004], 1.2.4 Unless contraindicated, offer nicotine replacement therapy, varenicline or bupropion as appropriate to people who want to stop smoking, combined with an appropriate support programme to optimise smoking quit rates for people with COPD. PDE4 inhibitors in COPD: a more selective approach to treatment. Culpitt SV, Rogers DF, Shah P, de Matos C, Russell REK, Donnelly LE, Barnes PJ. Definition of abbreviations: NK-κB, nuclear factor-κB; TNF-α = tumor necrosis factor-α. In the absence of significant contraindications, use oral corticosteroids, in conjunction with other therapies, in all people admitted to hospital with a COPD exacerbation. Thus, total PDE activity in human lung extracts is inhibited by only approximately 5 to 10% by therapeutic concentrations of theophylline (20). It recommends changes to usual practice to maximise the safety of … For people who have used 3 or more courses of oral corticosteroids and/or oral antibiotics in the last year, investigate the possible reasons for this. 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. To find out why the committee made the 2018 recommendations on lung volume reduction procedures, bullectomy and lung transplantation and how they might affect practice, see rationale and impact. A major limitation to the use of theophylline is the frequency of adverse effects (56). 1.2.16 For people with COPD who are taking LAMA+LABA, consider LAMA+LABA+ICS if: 1.2.17 These findings suggest that theophylline has the potential to “unlock” the resistance to corticosteroids that is seen in patients with COPD. It is still widely prescribed worldwide, because it is inexpensive. Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. Even in the resting state, histones are acetylated, and small differences in the number of acetylated histones result in relatively large biophysical changes (50). This effect may be mediated via PDE inhibition (26), although this has not been seen at the low doses that are effective in asthma (27). Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding. There appears to be a relatively selective effect on Class I HDACs, with less effect on Class II HDACs (49). Although adenosine has little effect on normal human airway smooth muscle in vitro, it constricts airways of patients with asthma via the release of histamine and leukotrienes, suggesting that adenosine releases mediators from sensitized mast cells (22). 1.2.67 [2004]. NICE has produced a COVID-19 rapid guideline on community-based care of patients with chronic obstructive pulmonary disease (COPD). [2004], 1.3.35 Consider NIV for people who are slow to wean from invasive ventilation. To find out why the committee made the 2018 recommendations on education and how they might affect practice, see rationale and impact. Theophylline is the best … Polson JB, Kazanowski JJ, Goldman AL, Szentivanyi A. Inhibition of human pulmonary phosphodiesterase activity by therapeutic levels of theophylline. [2004], 1.2.37 Take particular caution when using theophylline in older people, because of differences in pharmacokinetics, the increased likelihood of comorbidities and the use of other medications. 1.2.46 Consider azithromycin (usually 250 mg 3 times a week) for people with COPD if they: have optimised non-pharmacological management and inhaled therapies, relevant vaccinations and (if appropriate) have been referred for pulmonary rehabilitation and. [2010], 1.1.7 Think about a diagnosis of COPD in younger people who have symptoms of COPD, even when their FEV1/FVC ratio is above 0.7. Devereux G, Cotton S, Barnes P, et al. Clinical guideline [CG101] Published date: 23 June 2010. [2004]. [2018], 1.2.64 To ensure everyone eligible for long-term oxygen therapy is identified, pulse oximetry should be available in all healthcare settings. [2004]. In this section of the guideline, the term theophylline refers to slow-release formulations of the drug. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. [2004], 1.3.45 Give people (or home carers) appropriate information to enable them to fully understand the correct use of medications, including oxygen, before discharge. Because of the problems with side effects, there have been attempts to improve on theophylline, and there has been increasing interest in the development of selective phosphodiesterase (PDE) inhibitors. Pulmonary rehabilitation is not suitable for people who are unable to walk, who have unstable angina or who have had a recent myocardial infarction. 1.2.1 For guidance on the management of multimorbidity, see the NICE guideline on multimorbidity. 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