Systematic Review of Pain in Clinical Practice Guidelines for Management of COPD: A Case for Including Chronic Pain?

Chronic pain is highly prevalent and more common in people with chronic obstructive pulmonary disease (COPD) than people of similar age/sex in the general population. This systematic review aimed to describe how frequently and in which contexts pain is considered in the clinical practice guidelines (CPGs) for the broad management of COPD. Databases (Medline, Scopus, CiNAHL, EMbase, and clinical guideline) and websites were searched to identify current versions of COPD CPGs published in any language since 2006. Data on the frequency, context, and specific recommendations or strategies for the assessment or management of pain were extracted, collated, and reported descriptively. Of the 41 CPGs (English n = 20) reviewed, 16 (39%) did not mention pain. Within the remaining 25 CPGs, pain was mentioned 67 times (ranging from 1 to 10 mentions in a single CPG). The most frequent contexts for mentioning pain were as a potential side effect of specific pharmacotherapies (22 mentions in 13 CPGs), as part of differential diagnosis (14 mentions in 10 CPGs), and end of life or palliative care management (7 mentions in 6 CPGs). In people with COPD, chronic pain is common; adversely impacts quality of life, mood, breathlessness, and participation in activities of daily living; and warrants consideration within CPGs for COPD.

: The clinical practice guidelines for the management of chronic obstructive pulmonary disease (COPD) included in this review.

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Chronic Obstructive Pulmonary Disease: Official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care 2013 Czech Republic [29] Diagnosis and Management of Chronic Obstructive Pulmonary Disease: The Swiss Guidelines 2013 Switzerland [30] 慢性阻塞性肺疾病诊治指南(2013 年修订版) (Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (Revised 2013)) 2013 China [31] Guía Portugal [34] (COPD national academic policy and guidelines for prevention, diagnosis, and care) 2012 Norway [35] Chronic Obstructive Pulmonary Disease 2012 Michigan: USA [36] PCO Prise en Charge De la Broncho-Pneumopathie Chronique Obstructive Guide pratique à l'usage du praticien (Chronic Obstructive Pulmonary Practice Guide for the Practitioner) 2012 Algeria [14] Danske KOL-Guideline (Danish COPD guideline) 2012 Denmark [37] Recomendaciones para la prevención, diagnóstico y tratamiento de la epoc en la Argentina (Recommendations for the prevention, diagnosis, and treatment of COPD in Argentina)

2012
Argentina [38] Diagnosis  [39] Guideline for the management of Chronic obstructive pulmonary disease-2011 update 2011 South Africa [40] Chronic obstructive pulmonary disease (COPD) 2011 BC: Canada [41] Guía de práctica clínica Diagnóstico y tratamiento de la enfermedad pulmonar obstructiva crónica(Clinical Practice Guideline Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease) 2011 Mexico [42] 5 Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care 2010 United Kingdom [43] Richtlijn Diagnostiek en behandeling van COPD (Guideline for the diagnosis and treatment of COPD)  In section Oral Bronchodilators, Phosphodiesterase type-4 Inhibitors, "Drug related adverse effects mainly affect the gastrointestinal system; diarrhoea, abdominal pain, nausea and vomiting and weight loss are approximately twice as common in subjects taking PDE-4 inhibitors as in those taking placebo." p. 39 Drug adverse effects (phosphodiesterase-4 inhibitors) In section Palliation and End of Life Issues, "The World Health Organisation defines palliative care as an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual." p. 71 Palliative care for management and assessment (non-specific) In section Confirm Exacerbation and Categorise Severity, Arterial Blood Gas, "The primary reasons for preferring VBG (over ABG) samples cited by the authors were less pain and lower risk of bruising." p. 100 Lung function testing indication/contraindication NHG: In section Diagnosis, "In the case of differential diagnosis between COPD and heart failure, pay attention to cardiovascular risk factors or conditions in the history, such as hypertension, a myocardial infarction or angina pectoris, and ask for topical complaints, such as palpitations or chest pain that fits angina pectoris." Physician visit to assess for differential diagnosis (chest pain) In section Evaluation, "In differential diagnostics, the following conditions are particularly important: * Lung carcinoma; their suspicion may be based on symptoms (haemoptysis, altered cough pattern, chest pain, weight reduction) or on a chance finding on a chest X-ray…." Physician visit to assess for differential diagnosis (chest pain) Saudi Arabia [16] 2014 1 In section Phosphodiesterase-4 Inhibitors, "The most common side effects are nausea, abdominal pain, diarrhea, reduced appetite, headache, and sleep disturbance. Most of these adverse effects improve over time. Mild weight reduction was also reported." p. 62 Drug adverse effect (phosphodiesterase-4 inhibitors) In section: What are Symptoms of COPD? "Chest Pain and Haemoptysis: These are not the usual symptoms of COPD. Their presence is often a pointer to an alternative diagnosis e.g., lung malignancy, PTB etc.)." p. 18 Physician visit to assess for differential diagnosis (chest pain) In section What are the Surgical Treatments that can be Offered for the Treatment of COPD?, "Bullectomy: Bullectomy. The presence of large bullae is one of the common findings in patients with COPD. However, extensive data on the natural history of bullae is not available. Generally, enlargement of these bullae occurs, with complications like dyspnoea, haemoptysis, chest pain and pneumothorax. Some the accepted indications for bullectomy are the presence of single large bullae compressing the remaining lung, breathlessness due the bulla, haemoptysis, and reduction in the FEV1 to <50%." p. 41 Symptom of COPD (from bullae) In section Palliative and End of Life Care in COPD, Palliative care for management "Palliative care should be integrated within the treatment plan for patients with COPD [9][10][11] and be initiated when symptoms such as dyspnea, pain, depression, anxiety and constipation are not completely controlled by standard pharmacological treatment. The term palliation encompasses interventions aimed at preventing and relieving patient suffering through symptom control, so as to stabilize or improve quality of life." p. 10 VA/DoD: "One observational study of 242 patients found 10% of patients admitted with COPD exacerbation actually met standard criteria for myocardial infarction (chest pain combined with elevated troponin and/or electrocardiogram changes). Therefore, it is important to exclude a myocardial infarction in patients with COPD who present with symptoms and signs suggestive of an exacerbation." p. 25 Physician visit to assess for differential diagnosis (chest pain) Following recommendation: We suggest against offering roflumilast in patients with confirmed, stable COPD in primary care without consultation with a pulmonologist. (Weak Against) "In general, adverse events were more common in patients receiving roflumilast compared to placebo. Gastrointestinal events such as diarrhea, nausea, vomiting, dyspepsia, and abdominal pain were observed more frequently in patients treated with roflumilast than placebo." p. 33 Drug adverse effects (phosphodiesterase-4 inhibitors) In  In Table 1 Highlights of major comorbidities in COPD patients, "Ischemic heart disease: Diagnostic features: Some common symptoms with COPD: chest pain in exacerbations, dyspnea as anginal equivalent." p. 4 (English 2014 guideline) Physician visit to assess for differential diagnosis (chest pain) Czech Republic [29] 2013 1 In section Palliative Care in COPD, "An important part of palliative care is the administration of opioids (orally, transdermally or parenterally), first justified in discussion with the patient's family or the patient himself/herself. The main rationale for the use of opioids in this situation is sedation and inhibition of pain (e.g. from compressive spinal fractures), and otherwise unmanageable sensation of dyspnoea. Monitored administration of benzodiazepines is also effective at this stage of the disease. Very severe dyspnoea treatment can be supported with inhalation of furosemide and several other non-pharmacological methods-e.g. by cooling the face." p. 197 Palliative care for management-with opioids In Guideline Preface, "In order to regulate chronic obstructive pulmonary disease, diagnosis and treatment, to ensure the quality of medical care, improve the level of clinical work, and thus effectively reduce the patient's pain, improve the quality of life, reduce the death of the disease rate, reduce the burden of disease, 1997 Chinese Medical Association Respiratory Diseases The club has organized relevant experts from China to refer to international experience and combine the actual situation in China has formulated the diagnosis and treatment of chronic obstructive pulmonary disease." Non-specific management (goal) In section Diagnosis and Differential Diagnosis, "Comprehensive collection of history to assess the diagnosis of chronic obstructive pulmonary disease, the first should be a comprehensive collection of medical history, including .other non-Physician visit to assess for differential diagnosis (chest pain) specific symptoms (wheezing, chest tightness, chest pain and morning headache, but also pay attention to the history of smoking (in terms of the year) and occupational, environmental exposure of harmful substances such as history." p. 70 In section Phosphodiesterase-4 (PDE-4) Inhibitor "Adverse reactions: the most common are nausea, loss of appetite, abdominal pain, diarrhea, sleep disorders and headaches…" p. 73 Drug adverse effects (phosphodiesterase-4 inhibitors) Chile [32]  In section Recommendations for Diagnosis, "When considering a COPD diagnosis, check for the presence of the following factors: weight loss, stress intolerance, nocturnal arousals, ankle inflammation, occupational hazards, chest pain, hemoptysis (11)." p. 16 Physician visit to assess for differential diagnosis (chest pain) In section Treatment of COPD Exacerbations, "Chest pain and fever are uncharacteristic for exacerbation of COPD and should be induced to find another cause of the disease." p. 84 Physician visit to assess for differential diagnosis (chest pain) In section COPD Diagnosis, "Patients who are suspected of COPD should also be asked about the following factors: …Is there a chest pain? … Note: The last two symptoms are uncharacteristic for COPD and, in their presence, the probability of another disease increases." p. 18 Physician visit to assess for differential diagnosis (chest pain)

Norway [35] 2012
In section Other Diseases, "Diseases that may give similar symptoms as COPD and which must be ruled out are heart failure, pulmonary artery disease (sarcoidosis, pulmonary fibrosis), sequela after tuberculosis, cystic fibrosis and tumors of the trachea and main bronchi. In exertion-related chest pain in addition to shortness of breath, coronary heart disease must be considered, while hemoptysis may include acute respiratory infection, pneumonia, lung cancer or pulmonary embolism." p. 31 Physician visit to assess for differential diagnosis (chest pain) In section Laboratory Test, "The test (cardiopulmonary exercise test) can tell whether it is the cardiocirculatory system, lung function, weight, ventilation/hypoxia/hypercapnia, peripheral muscle, pain in the musculoskeletal system, motivation/anxiety or irregular breathing patterns, or various combinations of these factors that explain a person's functioning." p. 53 CPET for pain assessment as exercise limitation In section Secretion Mobilisation, Techniques for Secretion Mobilisation, Positive Expiratory Pressure (PEP), "For PEP the respiratory tract is kept open during the exhalation and increased pressure with improved air supply to the alveoli can contribute to stretch expansion of atelectatic lung tissue. In practice, PEP is a suitable aid for patients with difficulty to increase ventilation due to low level of function, overweight, pronounced fatigue or pain in the thorax." p. 55 Alternative management strategy for patients with pain In section Systemic Drug Therapy, Phosphodiesterase Inhibitors (PDE4), "The most common side effects are nausea, abdominal pain, diarrhoea, sleep disorders and headaches. The side effects are early treatment is reversible and may decrease with prolonged use." p. 86 Drug adverse effects (phosphodiesterase-4 inhibitors) In section Osteoporosis and Fractures, "COPD patients are at increased risk of osteoporosis and fracture. In patients with severe COPD have almost 70% osteoporosis or osteopenia. Hip fractures contributes to an already reduced mobility, while compression breaks, beyond pain and functional limitation, also contribute to increasing kyphosis of the thoracic spine, and develop an addition of a spirometric restrictive component and hence more breathing difficulties." p. 106

Complication of COPD
In section Symptoms and Treatment Measures at Terminal COPD, "The main distressing symptoms in advanced COPD include fatigue, shortness of breath, anorexia, depression, insomnia, pain and dry mouth/thirst." p. 117

Symptom of COPD
In section Opiates, "The main drugs for the relief of heavy breathing are opiates… The dosage of morphine is lower than in pain…." p. 118 Non-specific pain management-reference to opioid dose In section Appendix, Borg CR10 Scale, "Instruction: You should use this scale to tell how strong your experience or feeling is. It can apply your experience of effort, pain, difficulty or anything else." p. 143 Rating scale for pain assessment (non-specific context) In section Appendix, Borg CR10 Scale (explanation of the tool), "…The experience of the effort depends primarily on the fatigue in your muscles, whether you feel breathless and eventual pain." p. 144 Rating scale for pain assessment (non-specific context) Algeria [14]  In the definition for Palliative Care, "Palliative care: Care aimed at alleviating symptoms, pain and distress, and hence improving quality of life, rather than at curing or slowing progression of a disease or condition. It is often associated with, but is actually not limited to, the end of life." p. 48 Palliative care for management In section Symptoms, "Patients in whom a diagnosis of COPD is considered should also be asked about the presence of the following factors: chest pain." p. 63 Physician to assess for differential diagnosis (chest pain) In section Symptoms of an Exacerbation, "Chest pain and fever are uncommon features of COPD exacerbations and should prompt a search for other aetiologies." p. 356 Physician to assess for differential diagnosis (chest pain) In section Oxygen Therapy during Exacerbations of COPD, "Radial stabs to obtain blood for arterial blood gas analysis are not more painful than arterialised ear lobe gases." p. 384 Lung function testing indication/contraindication (blood gas) In section Oxygen Therapy during Exacerbations of COPD "Arterialised ear lobe samples are an alternative way of obtaining arterial blood gases if there is local expertise and may be less painful for patients." p. 384 Lung function testing indication/contraindication (blood gas) 15 NVALT: Netherlands [44] 2010 10 In section Recommendation, "People with a mucus problem can be stimulated to be active and move in addition to other interventions. Using a simple questionnaire can get an impression of the problems that the patient experience and whether a reference here is useful: Questions concerning sputum retention: -Do you regularly cure (daily) mucus? -Can you easily cough or take a lot of effort? -How long are you coughing up in the morning? -Is it ever black for the eyes when coughing? -Are you very tired or short-tempered after coughing? -Is coughing painful? -Is the sputum tough?" p. 106 Questionnaire for assessment (painful cough for mucus clearance) In section Quality of Life of People with COPD, "People with mild to moderate COPD treated in general practice score lower on almost all dimensions of quality of life, certainly in comparison with people with asthma. In the patient panel chronic diseases people with COPD were compared with people with other chronic disorders (not asthma) with regard to a number of important aspects of the chronic disease. The differences between the two groups are not large. However, COPD patients believe that the disease will progressively deteriorate, see more physical limitations, but experience less pain and are of the opinion that their disease can be better controlled by medical treatment than people with other chronic conditions (Patiëntenpanel, 2000)." p. 124

Symptom of COPD
In section Quality of Life in Patients with COPD: Psychological Well-Being, Other Considerations, "If the patient experiences dyspnoea, the doctor should ask to what extent this leads to feelings of anxiety and worry (real or unreal). Also ask under which circumstances this is most common (ie physical exertion). Accompanying symptoms that the doctor asks about or in which he should think of the existence of an anxiety disorder are: palpitations, perspiration, tremor, pain, upset stomach, tingling, deaf feelings, heat or cold sensations, de-realization or depersonalization feelings, restlessness, being quickly tired, concentration problems, irritability, sleep problems. Depending on the severity, duration and course of the complaints, the influence Physician visit to assess for differential diagnosis (anxiety) on social functioning, and avoidance of certain situations or activities, the doctor decides whether targeted treatment is necessary." p. 129 In section Diagnosis for Lung Rehabilitation, Screening, Other considerations, "One problem with the screening lists is that lung patients often report thoracic pain. A complication is that exercise tests are not only time consuming, But also require expertise and medical supervision. Standard ergometric screening therefore rely heavily on capacity. For lung patients, (risk) groups should be defined based on the severity of the disorder (effort, desaturation), cardiovascular co-morbidity and training intensity." p. 190 Physician visit to assess for pulmonary rehabilitation In In section Palliative Care, "Dyspnoea, fatigue, depression and pain are the most common symptom in patients in the year before death." p. 24

Symptom of COPD
In section Bronchodilators-Theophylline, "Significant undesirable effects of Theophylline therapy are nausea, vomiting, abdominal pain, sleep disorders, muscle cramps, hypokalaemia and tachycardic heart rhythm disturbances, which occasionally already at serum concentrations in the therapeutic range." p. 41 Drug adverse effects (methylxanthines)