Abstract
Patients with lung cancer have high mortality and high morbidity. Lung cancer-related symptoms and problems such as dyspnea, fatigue, pain, and cachexia that begin in the early phase later result in poor physical functioning, psychosocial, and quality of life status. In addition, advancing age is associated with significant comorbidity. These patients may benefit from multidisciplinary therapy to reduce the perceived severity of dyspnea and fatigue and increase physical functioning and quality of life. Based on management of symptoms and problems such as dyspnea, physical inactivity, cancer-related fatigue, respiratory secretions, pain, and anxiety–depression of these patients, it is thought that physiotherapy techniques can be used on advanced lung cancer patients following a comprehensive evaluation. However, well-designed, prospective, and randomized-controlled trials are needed to prove the efficacy of physiotherapy and pulmonary rehabilitation in general for patients with advanced lung cancer.
Introduction
Lung cancer is the most common type of cancer. It is responsible for more cancer-related deaths than the total of the other common cancers such as breast, prostate, and colorectal cancer. 1 Patients with lung cancer have a high mortality as well as high morbidity. In most of the patients, cancer-related symptoms are seen. These patients confront problems such as dyspnea, fatigue, pain, and cachexia especially in the late phase. These symptoms and problems that begin in the early phase compromise compliance with treatment causing poor physical functional condition accompanied by psychosocial disorders and briefly negatively affect the quality of life of patients with advanced lung cancer who have limited life expectancy.2,3
Pharmacological and nonpharmacological therapies focus on increasing physical function and improving quality of life. 4 Pulmonary rehabilitation decreases respiratory symptoms and improves functional exercise capacity and increases quality of life, especially in chronic obstructive pulmonary disease (COPD). 5 Patients with lung cancer, like COPD, frequently suffer from symptoms such as dyspnea, fatigue, deconditioning, exercise intolerance, malnutrition, impaired life status, and quality. It has been found that COPD is present in 73% of male and 53% of female patients with lung cancer. 6 It is obvious that when COPD accompanies the disease, the systemic effects of COPD (peripheral muscle dysfunction, osteoporosis, loss of nonfat body mass, anxiety, and depression) will intensify the symptoms and problems of lung cancer. 7
The value of rehabilitation has been described in the context of thoracic surgery including lung resections, volume reduction surgery, and lung transplantation.5,8 However, in relation to patients with advanced lung cancer, there have been only a limited number of studies that explore the effectiveness of pulmonary rehabilitation. The adaptation and implementation of pulmonary rehabilitation is thought to be possible and effective.2,6,7,9–12 In this article, only the physiotherapy aspects of pulmonary rehabilitation applied to lung cancer will be discussed.
Dyspnea
Dyspnea is one of the most distressing symptoms in advanced lung cancer, and treatment of this symptom may be difficult and complex. 3 Although the severity of dyspnea in lung cancer varies according to the disease’s stage and progress, it has been suggested that 78% of the patients with advanced lung cancer have dyspnea. 13 Once diagnosed with lung cancer fatigue, pain, anorexia, coughing, and insomnia are the most frequent problems. In the later phase, dyspnea, pain, noisy breathing, and psychological stress frequently cause problems.14,15 It has been determined that dyspnea is seen in every stage of lung cancer and is associated with patients’ quality of life.16–18 Dyspnea in cancer patients is caused by associated conditions and diseases such as the cancer itself, the treatment, COPD, cardiac failure, anxiety, and the patient’s behavioral responses to other symptoms of the disease. 19
Nonpharmacological approaches are preferred to pharmacological ones such as opioids or anxiolytic medication, which is used to reduce dyspnea caused by respiratory depression. 20 There are a variety of methods and strategies to reduce dyspnea among COPD patients that are proved to be effective.14,21 Educating the patient and his or her family about arranging the humidity and temperature of the patient’s room, preventing noise, and creating a relaxing environment with music are useful suggestions.14,21,22
Anxiety, depression, and other psychological factors occur frequently in patients with advanced lung disease and influence breathlessness. 22 Therefore, breathing control and relaxation therapy may be beneficial for both the individual and the family.23,24 It has been shown that a forward leaning position is a particularly effective strategy to reduce dyspnea. Forward leaning is associated with a significant reduction in electromyographic activity of the scalenes and sternomastoid muscle, an increase in transdiaphragmatic pressure and inspiratory mouth pressure, and significant improvement in thoracoabdominal movements. This position has been shown to improve diaphragmatic function and hence improves all chest movements and decreases accessory muscle recruitment and dyspnea. 25
It has been shown that fanning cold air on the nose, mouth, and chin reduces dyspnea perception. It has been thought that cold air circulation changes patients’ dyspnea perception by stimulating extrathoracic mechanoreceptors on the face or within the nasal passages. 26 The usage of a small, portable, and cheap fan may decreasing dyspnea even among advanced lung cancer patients.26–28
Acupuncture may be an alternative approach to reduce breathlessness, but the data are limited and mixed.28,29
A number of studies have shown that the pursed lip breathing technique is particularly helpful in reducing or settling dyspnea.20,25,30,31 Other studies on breathing training has observed that when breathing training is applied to patients (panic management, pursed lip breathing, and diaphragmatic breathing), their respiratory rate dyspnea decreases dramatically and their functional capacities improve.21,28,31,32
At present there is no information about the application and effects of inspiratory muscle training on lung cancer patients with chronic pulmonary disease. When the advantages and benefits of this technique are considered, it is assumed that it can be used with an exercise program on advanced lung cancer patients. 33 Inspiratory resistive training was used only in one study on a pulmonary rehabilitation program for nonsmall cell lung cancer (NSCLC) patients who had undergone lung resection, but the effects of the application alone are not stated. 34
It has been stated that lung cancer patients employ an avoidance of activity strategy so as to prevent dyspnea and this situation causes a sedentary lifestyle and deconditioning. 35 Therefore, it would be useful to inform the patients about energy conservation techniques in order to increase their physical condition.20,36 Recommending portable oxygen support and/or assistive tools for walking (walkers, wheelchairs, rollators, etc.) when necessary and giving the patients breathing control training during activities are other assistive strategies for reducing dyspnea.23,37 It has been found that pursed lip breathing taught during walking activity reduces the severity of dyspnea in COPD patients and increases the walking distance. 38
Physical inactivity
Particularly in the advanced stage, the lung cancer patients’ physical abilities reduce due to the symptoms of the illness and problems caused by the treatment. 39 It has been determined before that the physical activity level is relevant to the quality of life.4,15,17,39
It is thought that in these patients skeletal muscle dysfunction arises from skeletal myopathy (due to use of oral corticosteroids), deconditioning (from physical inactivity), and high levels of systemic inflammation (from underlying disease and therapy). 40 For these reasons, exercise training should be applied in every stage of the disease. It has been proved that exercise training frequently applied in pre- and postoperative periods decreases the symptoms of lung cancer patients and improves exercise capacity and quality of life.41,42 But, generally there is no clear information about the content of exercise programs that should be applied in advanced lung cancer patients. When skeletal muscle influence on patients is suggested, resistance exercises should also be applied. It is thought that the combination of aerobic and resistance training may be the most effective form of exercise training to optimally augment peak oxygen consumption in patients with lung cancer. It is believed that the suggested comprehensive program will improve oxidative capacity, additionally increase muscle strength and endurance, reduce fatigue, and improve exercise tolerance.43,44 It is determined that aerobic and resistance exercise with exercise training frequently used with breast cancer patients increase their cardiopulmonary capacity and quality of life, reduce fatigue, improve physical functional levels, and cure psychological problems (resulting in regular sleep patterns, general well-being, self-confidence, energy, and so on). 45 Although there are differences in intensity and frequency in exercise training studies, it should be noted that exercise applied in cancer patients should not cause over fatigue and should be programmed individually according to patients’ tolerance.10,11,43–47 In accordance with this purpose, it is thought that interval exercise programs may be more suitable and beneficial for lung cancer patients instead of continuous exercise. 47 It has been identified that interval exercise programs that can be applied even in severe COPD patients improve the quality of life and are safe and beneficial. 48 Moreover, it has been found that one-legged exercise training, which is a new exercise strategy used in severe COPD patients, causes lower ventilatory stress than conventional bipedal cycling and also increases aerobic capacity much more. 49 Also, this exercise strategy is appropriate especially for advanced lung cancer patients. There is a need for more research into this subject.
Although some research shows that multidimensional exercise programs are suitable for patients with lung cancer, exercise adherence is considerably low (19–44%).50,51 Even though supervised outpatient exercise programs are preferred for patients with comorbid disease and poor health, community-based programs are thought to be more acceptable and more feasible for patients undergoing chemotherapy. For this reason, improving low intensity and more appropriate programs, especially for patients with advanced lung cancer who are undergoing chemotherapy, is necessary. There is no information about home-based exercise training for these patients. However, it has been proved that home-based exercise programs are feasible and improve functional status and quality of life in patients with breast cancer and reduce cardiac dysfunction.2,52,53
A few studies have described the effectiveness of exercise in patients with advanced lung cancer. 8 Spruit et al. 54 researched the multidisciplinary inpatient rehabilitation program’s effects in NSCLC patients with comorbidity such as COPD, arterial hypertension, and transient ischemic attack. Exercise training consisted of daily cycle ergometry, treadmill walking, weight training, and gymnastics. The impairment of pulmonary function was unchanged, while significant improvements were found in the 6-minute walking distance and peak cycling power output. 54 Jones et al. 55 applied an aerobic exercise program to 19 lung cancer patients (I–III B NSCLC). Significant improvements in quality of life, exercise performance, and fatigue severity of patients were reported. 55 Cesario et al. 34 applied a multidisciplinary inpatient pulmonary rehabilitation program to 25 NSCLC patients who had undergone lung resection. It was found that walking distance was significantly improved despite there being no change in pulmonary function. 34 Ozalevli et al. 11 enrolled 18 patients with stage IIIA–B and IV advanced lung cancer who did not have surgical indications and received intense chemotherapy and radiotherapy in an inpatient chest physiotherapy program. Although there was no change in pulmonary function at the end of the program, a significant decrease in severity of fatigue and dyspnea was perceived by patients, and a significant increase in their quality of life and exercise capacity was determined. 11 Riesenberg and Lübbe 56 applied an aerobic exercise program to 45 multimorbid lung cancer patients who had undergone surgery and/or radiotherapy and/or chemotherapy. It determined that after increased work performance by bicycle ergometry and a 6-minute walk test (functional status), heart rate at rest was reduced, quality of life was improved, and fatigue was reduced. 56 Temel et al. 50 enrolled 25 patients with advanced lung cancer (advanced NSCLC, stage IIIB with pleural or pericardial effusions or stage IV), who were receiving chemotherapy, in an aerobic and strength-training exercise program. Authors have stated that this program is applicable in patients with advanced lung cancer. 50
Interestingly, it is observed in the studies that cycle ergometer is preferred over treadmill walking. Exercise intensity can be arranged more accurately and monitoring of patients is easier. Besides, the cycle ergometer is a more appropriate exercise device than the treadmill because most of the patients with lung cancer are old and probably suffer from balance problems. 43 There is not enough information about exercise and physiotherapy approaches for patients with advanced lung cancer, especially during chemotherapy. But it has been said that to protect physical performance, despite chemotherapy-related over fatigue and exhaustion, aerobic exercises can be appropriate and effective in this period.57,58 It has been stated through research that aerobic exercise, massage, relaxation, and body awareness training in advanced lung cancer patients undergoing chemotherapy especially decrease fatigue symptoms and help to cope with symptoms.2,57 Generally in this period, doing exercises in rhythmic contraction without increasing fatigue and low rhythm with relaxation in the applied aerobic exercise programs is suggested. 58
In patients with advanced lung cancer, mobilization, with or without oxygen, of patients who suffer particularly from severe deconditioning is useful. It is stated that applied passive or active assistive exercises used for preventing muscular atrophy can be beneficial for severe lung cancer patients who cannot do active muscle contraction effectively. In these cases, it has been shown that neuromuscular electrical stimulation (NMES) is also effective. 59 Several investigators have shown that NMES intervention is well tolerated and effective alone or in combination with exercise, results in improvements in strength, muscle mass, exercise capacity, and sense of dyspnea during daily living activities in patients with very severe COPD, chronic heart failure, and mechanically ventilated intensive care unit patients who experience intolerable symptoms during or after active training due to the progression of their underlying disease.12,22,60,61 It has been suggested that applying the NMES as a home-based NMES program maintains and improves quadriceps femoris muscle strength in patients with lung cancer.62,63 Randomized-controlled trials are needed to study the efficacy and safety of NMES for severely disabled lung cancer patients.
A small number of studies have shown that pulmonary rehabilitation reduces perioperative risks and improves functional capacity in patients with lung cancer. Pulmonary rehabilitation is suggested as a feasible and safe therapeutic treatment in patients with lung cancer. 8 However, there is not much literature about the effectiveness and content of pulmonary rehabilitation in patients with advanced lung cancer. Well-designed, further research is needed to expand the role of pulmonary rehabilitation and special exercise programs in patients with advanced lung cancer.
Cancer-related fatigue
One of the most common and distressing effects of cancer is fatigue. Cancer-related fatigue is defined as “an unusual persistent subjective sense of tiredness” arising directly and/or indirectly from cancer or its treatment. 53 This symptom occurs from the earliest stages of the disease and affects patients negatively. 64 A study defined that 57% of the patients with stage 1A-1B NSCLC have fatigue according to Brief Fatigue Inventory. It has been stated that the high level of fatigue despite the early stage of disease causes the impaired functional status of the patients. 65
It has been found that physical functioning of patients with advanced lung carcinoma decreased due to fatigue. The fatigue was not caused by weight loss and anemia but was related to psychological factors. 66 In a study conducted in ambulatory patients with advanced lung cancer, stage lllA–B, IV suffered from 81.5% fatigue and accompanying 74.5% dyspnea and 65% pain symptoms. It was found that approximately one-third of patients with fatigue had limited daily life activities such as walking due to fatigue, which also affected the emotional state of the patients in a negative way. 15
As well as resulting from the cancer itself, there can be many reasons for cancer-related fatigue such as anemia, medications, changes in metabolism, infection, dehydration, loss of strength and muscle coordination, decline in physical condition, emotional distress, trouble sleeping, inactivity, pain, poor nutrition, and other comorbidities or medical conditions in addition to cancer. 67 Cancer-related fatigue is a complex problem with physical and psychosocial influences. Thus, the therapies and strategies to be used to reduce fatigue must be considered in a multidirectional and comprehensive manner.
To combat cancer-related fatigue, the stage of the disease, treatment regimes, age factor, fatigue-aggravating dyspnea, pain, vomiting and such problems, the severity of these problems, and the quality of life of the individual must be assessed comprehensively. Based on this assessment, exercise training, diet therapy, sleep therapy, cognitive therapy, and pharmacological therapy can be individually adjusted and applied to reduce cancer-related fatigue. 68
Nonpharmacological interventions for fatigue consist of education, counseling, and support groups for stress reduction and energy conservation, nutrition, and exercise. It is believed that exercise changes the negative neuromuscular influence caused by the disease. Thus, fatigue can be reduced with regular exercise. It has been shown in patients with COPD that exercise training for at least 4 weeks, with or without education and/or psychological support, leads to a clinically significant reduction in fatigue, as well as improving dyspnea, emotional function and patients’ sense of control. 69 There is some evidence to support the use of exercise for cancer-related fatigue, although the role of exercise for patients with lung cancer specifically has not been examined. Exercise would likely provide a benefit to this patient population, although additional data are needed to support this.12,57,67,70,71
Chemotherapy-induced fatigue leads to physical discomfort and exhaustion, leading to reduced activity levels and avoidance of physical effort. 2 Despite this symptom, it has been found that aerobic exercise training applied in the chemotherapy period reduces psychological stress and perceived fatigue severity. 57 Moreover, moderate walking training as a home program decreases fatigue. 53 Exercise programs to reduce fatigue may not be appropriate for advanced lung disease, but it is assumed that fatigue can be reduced by addressing the symptoms of dyspnea, depression, and insomnia related to fatigue.72,73 In addition, understanding the underlying mechanisms for energy loss and gain, as well as the relationship between the right amount and type of activity and sleep, are important and can lead to more effective therapy programs. It is known that training in energy conservation techniques reduces fatigue and improves functional capacities, thereby maintaining symptom control.9,28,68,74 Energy conservation strategies can also be used for patients with advanced lung cancer.
Cough and respiratory secretions
Cough and excess secretions are a common and distressing symptom in patients with lung cancer. Both symptoms are seen particularly in patients in the late stages of lung cancer at an approximate rate of 40%. Lung cancer patients with underlying COPD can suffer from more severe cough with bronchial secretion. 75
Cough in patients with lung cancer results from pulmonary pathology (upper and lower respiratory infection, COPD, asthma or pulmonary edema, etc.), gastroesophageal reflux disease, aspiration, and some drugs (angiotensin converting enzyme inhibitor and nonsteroidal anti-inflammatory drugs, etc.). 14 Chronic and severe cough increases the cancer pain of patients with lung cancer, causes sleep deficit, dyspnea, and fatigue or increases their severity and causes anxiety.14,75 Even though in lung cancer, cough is helped with medication, it has been stated that hydration, gentle suctioning, postural drainage, chest physiotherapy, and external oscillation applications can be useful for patients with lung cancer, underlying COPD and bronchiectasis who have poor cough reflex to maintain bronchial hygiene.5,7,9,14,23,25,61 Unfortunately, there are no studies in this area. Since the risk of metastasis is high in patients with advanced lung cancer, it is sensible to avoid the percussive applications on the chest wall (percussion, vibration, etc.). 76 Although there is no related evidence, interpretation can be made for patients with lung cancer based on the application of the techniques that maintain bronchial hygiene in risky and complex diseases. For example, thoracic expansion exercise and breathing control may be helpful to assist in mobilizing secretions up the bronchial tree. Forced expiratory technique and coughing can be used to help the patient mobilize secretions. Forced expiratory technique consists of one or two huffs combined with breathing control. This technique can be used in any position according to the individual’s requirements, and studies have shown that there is no effect on hypoxemia. Besides, it has been stated that these techniques were used and proved effective in the acute exacerbation periods of patients with COPD.76,77 In addition to this, flutter, a device that is simple, easy to use, and self-applicable, increases sputum removal during treatment and diminishes total and peripheral airway resistance in hypersecretive patients. 78
Pain
It has been observed that 56% of patients with advanced COPD and cancer patients suffer from distressing pain. 13 Moreover, it has been found that 28% of lung cancer patients have severe pain. 79 Causes of pain in COPD include subcostal pain due to diaphragmatic and intercostal muscle fatigue, rib fractures related to coughing and/or corticosteroid-induced osteoporosis, and pleural inflammation caused by infection. 20 In patients with lung cancer, pain may be caused by tumor invasion into soft tissues, nerves or bone, either at primary site or from metastasis. 12 What is more, it is obvious that pain related to inactivity that develops as a result of dyspnea and fatigue will further reduce the quality of life of advanced lung cancer patients, most of whom also have COPD.
Pain reduction strategies used on patients with COPD can also be used on patients with lung cancer. It has been stated that biofeedback and breathing techniques can be effective in reducing the pain of cancer patients generally. 12 In particular, transcutaneous electrical nerve stimulation (TENS) may be helpful. It has been shown that TENS reduces the pain related with lung resection.60,80 Ozalevli at al. 11 reported that 77.8% of 18 advanced lung cancer patients who they monitored with an inpatient physiotherapy program suffered from pain, especially in the waist–hip and thorax regions. It was found that with the application of TENS (conventional TENS: 80 Hz, using square wave 100 microseconds pulses), the pain and its severity was reduced significantly, while the analgesic intake of the patients did not change. This study has shown that TENS can be safely used for the reduction of pain and is effective on patients with advanced lung cancer. 11 Massage can be a safe and effective application in palliation of symptoms and mood that occur in patients with advanced cancer. 81 It has been found that massage therapy (6 therapies every 2 weeks) significantly reduces the severity of the pain and improves the mood of patients with advanced lung cancer. 82
Anxiety and depression
It has been shown that, particularly in patients with advanced COPD, depression and anxiety increase the perceived dyspnea severity and associated with the poor physical, social and quality of life of patients.72,83 Similar to COPD, patients with lung cancer can also experience psychological morbidities like depression and anxiety. It has been stated that the most frequently used methods to reduce anxiety and depression are cognitive behavioral therapy and progressive muscular relaxation applications.20,53,66,84,85 Methods include progressive muscular relaxation with systematic tensing and relaxing of all muscle groups, visualization and guided imagery, self hypnosis, and distraction by music 20,28,86 It has been proved that the progressive muscular relaxation technique reduces anxiety, dyspnea, and heart and respiratory rate, especially in patients with COPD.25,59,84 It is acknowledged that this technique and teaching other relaxation methods and positions are advantageous and simple for COPD patients in that they require no devices and allow the patients self-control of symptoms. 25 However, it has been found that these applications are not effective in reducing anxiety and depression in advanced lung cancer patients. 87 They must be taught to the patients, practised, and adapted specifically to each individual at the earliest stage possible when there are no respiratory problems and/or the severity of the problem is at its lowest so that these approaches used for reducing symptoms and problems may prove effective.20,87
Besides, it has been shown that depression and anxiety reduce the physical activity level of an individual, and exercise cures these symptoms. 88 Exercising reduces anxiety and depression, perceived dyspnea severities and fatigue, and increases quality of life, especially in older COPD patients.12,89,90 The effect of exercise on depression and anxiety is, on the other hand, unknown in advanced lung cancer patients. Although the symptoms of fatigue, pain, and dyspnea of 171 advanced lung cancer patients at an age average of 63 were defined as low severity (1 to 3 on a 0–10 numerical scale), these symptoms proved significantly effective in their daily life activities, walking, working, and moods. Moreover, it has been detected that the dyspnea perception of patients is affected by their psychological state as well as by symptoms such as pain and coughing. It has been thought that, in these patients, reducing depression and anxiety decreases the severity of dyspnea and the negative effect of dyspnea on daily activities. 15 Briefly, curing symptoms like dyspnea, pain, and coughing that cause and are increased by psychological stress, especially in advanced lung cancer patients, will reduce the negative influence of the disease in its early stages. Or, the appropriate psychological support given, starting at the early stage of the disease, will definitely contribute to the treatment of patients. Comprehensive research is required on this topic.
Conclusion
Since the life span of even metastatic lung cancer patients is increasing, the need for satisfactory and effective applications to enhance the functional status and life quality of lung cancer patients from the earliest stage is necessary.
Due to the age factor, comorbid conditions, complex symptoms, and multiple factors resulting from the disease and treatment, the need for appropriate physiotherapy and rehabilitation applications, especially for advanced lung cancer patients whose care is difficult, is increasingly obvious. Since there are few studies on the topic, it is thought that physiotherapy techniques, the effectiveness of which has been proved in patients with severe pulmonary disease, can be used on advanced lung cancer patients. All the physiotherapy approaches should be planned and applied as individual programs tailored to these patients following a comprehensive evaluation. 90 However, well-designed, prospective, adequately powered and randomized-controlled trials are needed to prove the efficacy of physiotherapy and pulmonary rehabilitation in general for patients with advanced lung cancer.
Footnotes
Conflict of interest
The authors declared no conflicts of interest.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
