It constitutes a complex syndrome, which also includes anorexia.
However, nutritional abnormalities may occur much earlier in lung cancer , predating clinically evident cachexia In fact, people with lung cancer who are candidates for surgical lung resection i. Nutritional abnormalities associated to lung cancer are related to anorexia but also to a hypermetabolic status, where the host and the tumor compete for nutrients. This is especially dramatic in the case of proteins since their synthesis is decreased and breakdown is increased in cancer. Since skeletal muscles account for around half of the entire body protein content, it is easy to anticipate that muscle mass would be affected, leading to muscle dysfunction 4.
This muscle mass reduction and the subsequent muscle weakness appears to be the most relevant clinical event induced by cancer cachexia , since they result in significant impairment in quality of life, exercise capacity, physical functions and mortality - As for different muscle groups, patients with thoracic cancers have been shown to have lower quadriceps strength than healthy controls Regarding etiology for the preceding abnormalities, most of the factors already mentioned for other respiratory conditions are also present in lung cancer, which in addition is frequently associated to COPD.
These factors include, not only nutritional abnormalities but also a low level of physical activity and muscle deconditioning, tobacco exposure, systemic inflammation most likely, cytokines such as TNF-alpha or IL-1 and oxidative stress, aging, comorbidities and cancer treatments 4 , , Respiratory muscle function in turn will also be influenced by changes undergone by thorax mechanics as a result of the neoplasm and underlying disorders. Aging in particular is a factor that can contribute in a relevant way to sarcopenia and muscle dysfunction in patients with lung cancer.
Lung cancer treatment, which can include surgery, chemotherapy, radiotherapy and immunotherapy, is an additional factor that can contribute to nutritional and skeletal muscle abnormalities. Radiotherapy for instance can induce esophagitis-dysphagia and anorexia, whereas chemotherapy can cause nausea and vomiting, both affecting the ability to achieve an adequate dietary intake , As to surgical resection it involves the loss of lung function and respiratory symptoms, which in turn can lead to a reduction in physical activities as well as to cardiovascular and skeletal muscle deconditioning.
Finally, all these treatment regimens can increase the anxiety-depression symptoms linked to the diagnosis of lung cancer, also leading to a reduction in physical activity and social life. Interestingly, a systematic review indicates that dietary counseling or nutritional supplements can improve protein intake in patients undergoing chemotherapy The same review shows that these measures are able to maintain the nutritional status in lung cancer patients receiving radiotherapy These periods, characterized by the impairment of symptoms, can be present in different chronic respiratory conditions.
Exacerbations bring together many of the different factors that can contribute to nutritional abnormalities and skeletal muscle dysfunction 9. Exacerbations increase the level of local and systemic inflammation markers see previous sections 12 , as well as those of leptin. Moreover, anorexia, fever, reduced physical activity, a negative energy balance, increases in the work of breathing and use of systemic steroids are often added to this adverse metabolic picture, which negatively impacts on nutritional status and muscle function 9 , - It should be noted that muscle wasting and dysfunction can develop early in acute episodes, lasting for a relatively long time 9.
In fact, many authors consider that exacerbations are one of the factors that contribute the most to these abnormalities 9 , Conversely, those patients with muscle dysfunction show an increased risk of hospital admission due to these acute events , Acute exacerbations are also frequent in this disorder, being accompanied by many of the factors that are also present in COPD dramatic decrease in physical activity, increase in lung and systemic inflammation, metabolic derangement between energetic requirements and offers, drugs with potential negative effect on muscle tissue, etc.
Weight loss is so important in CF exacerbations that it has been included in its definition , having also specific therapeutic measures that have been incorporated in the guidelines As in other chronic respiratory disorders acute episodes are characterized by a marked catabolic state combined with reduced appetite and physical activity, and inflammatory events.
Moreover, insulin-requirements can be dramatically increased during CF exacerbations As a result of these factors, quadriceps maximal strength decreases acutely during the episode , , although it generally recovers in the follow-up The natural history of this disorder is highly variable, but some patients show acute deteriorations among periods of relative stability Although little is known about the pathophysiology of these acute events, it has been shown that systemic inflammation levels become increased As in the other disorders included in the present review, this factor would be added to a greater reduction in physical activity, impairment in gas exchange, and a worse nutritional balance.
The actual prevalence of nutritional deficiency in chronic respiratory conditions is relatively high, although precise rates depend mainly on the criteria used for the diagnosis. The simplest but less specific is to obtain direct or derived anthropometric variables. Other traditional anthropometric determinations are triceps skinfold or thigh circumference, but they have been progressively abandoned in the clinical setting. However, anthropometric measurements can be poorly sensitive to mild-to-moderate nutritional abnormalities. A more appropriate approach is to determine body composition using bioelectrical impedance or dual-energy X-ray absorptiometry DEXA 7 , Both methods provide an accurate approximation of fat free mass, which in the case of the latter technique can even offer compartmentalization in different body parts such as trunk, upper or lower limbs.
FFMI is the body composition variable most widely used to assess nutritional status.
It should be noted that diagnosis of nutritional deficiencies can be especially difficult in female patients, since they can show loss of muscle mass even though body weight remains relatively stable, showing significant discrepancies between BMI and FFMI Other methods that can also be used to assess nutritional status are imaging techniques computed tomography, magnetic resonance and ultrasounds , air displacement plethysmography ADP , deuterium dilution, and isotopic techniques 7 , 11 , , Blood determinations of serum total proteins, albumin fraction, cholesterol and prothrombin time can also be useful to complete the assessment of nutritional status 7.
Since this score involves multiple variables, a simplified version miniCASCO or MCASCO , which only involves body weight-lean mass, blood analysis and a short questionnaire, has also been recently developed for clinical purposes Although closely related, nutritional deficiencies and muscle dysfunction are not always associated. Thus, specific methods should be used to directly assess muscle function 12 , 13 Figure 2. Functional evaluation of respiratory muscles can be addressed with different approaches from clinical semiology to instrumentalized techniques. On the one hand, muscle dysfunction can be suggested by the presence of different symptoms and signs such as a very high respiratory rate with small tidal volume, a relevant worsening of dyspnea when lying in supine, the use of accessory muscles for ventilation, thoraco-abdominal or upper-lower chest incoordination, and difficulties in effective coughing Imaging techniques, such as conventional chest X-ray and ultrasounds, can also be useful to suggest the presence of respiratory muscle dysfunction , More specific are those techniques that allow determination of maximum respiratory pressures as an expression of muscle strength.
Their measurement at the mouth, using dynamic or static maneuvers i.
The chemotherapy regimen depends on the tumor type. Occupations involving exposure to coal, silica, and asbestos have long been recognized as causing lung disease classified within the ILD spectrum, and the term pneumoconiosis has been applied here as well e. As this has been written by practising dermatologists for practising physicians, a special emphasis has been laid on various therapeutic modalities. SCLC that originates from neuroendocrine cells may express CD56 , neural cell adhesion molecule , synaptophysin , or chromogranin. Strategies are presented for responding to referee comments, as well as ideas for developing discipline-specific English language skills for manuscript writing. Holland-Frei Cancer Medicine 8th ed. However, over the past 10—15 years, the term IPF in clinical pulmonary medicine, research studies and consensus statements has been restricted to a narrow and well-defined phenotype of disease, with specific clinical, radiologic, and histopathologic findings [ 4 , 5 , 6 ].
However, both can also be determined from FRC. MIP and MEP values can be expressed in absolute and relative terms since validated references exist for both variables , Validated reference values are also available in this case , Since all the above-mentioned measurements are valid only in the presence of normal upper airways, it may be necessary to perform a more invasive technique in some patients.
A common limitation to all these procedures is the need for patient collaboration. The latter is better tolerated since the former is uncomfortable and can even be painful 11 , Approximations to reference values with twitch stimulation of the diaphragm have also been published 13 , , Values lower than 50—60 cmH 2 O in men and 35—40 cmH 2 O in women are considered as indicative of diaphragm dysfunction, and below 15 cmH 2 O would evidence a serious muscle malfunction 11 , Less extended is determination of those variables that reflect muscle endurance.
The simplest are maximum voluntary ventilation MVV and maximum sustainable ventilation MSV , although they are both very unspecific A good alternative is determination of the time elicited by the patient sustaining a percentage of the maximum respiratory pressure until task failure Tlim - Functional assessment of peripheral muscles in turn, can also be approximated by clinical semiology. In this case, the presence of lower limb symptoms during even mild-to-moderate exercise or an evident loss of muscle mass are both suggestive of limb muscle dysfunction , Those techniques used to assess body composition, which have been detailed previously, can also help in the suspicion of an impairment in muscle function.
However, as occurs for respiratory muscles, there are specific tests to assess limb muscle function. The strength can be determined by dynamometry, generally using a maximal isometric maneuver. Handgrip is most often used for assessing upper limb strength, whereas quadriceps isometric contraction is usually employed for lower limbs Quadriceps strength can also be determined by measuring the peak torque at fixed joint angle speed , , although this technique requires more experience. Reference values are available for both handgrip and quadriceps dynamometers - As in the case of respiratory muscles, electrical or magnetic stimulation can be used in subjects unable to participate in the maneuver , , and reference values are also available 11 , Limb muscle endurance can also be approximated using procedures and variables very similar to those used with respiratory muscles e.
As so many factors can contribute to nutritional abnormalities and muscle dysfunction in chronic respiratory disorders, the therapeutic approach should be multidimensional Table 1. Unhealthy lifestyle must be modified and patients should increase their physical activity, improve the quality of their diet, and abstain from tobacco smoking and alcohol.
It is also important to prevent and appropriately treat exacerbations and avoid, or at least, reduce treatments with drugs that are deleterious to nutritional status and muscle function. When these measures become insufficient, dietary supplements or anabolic drugs can be used.
Similarly, training programs would contribute to reconditioning not only of the skeletal muscles but of the cardiovascular system. This simple measure is able to improve nutritional status and muscle mass and function through different positive effects On the one hand, it will eliminate the anorectic effect of tobacco, improving diet quality To cope with nutritional abnormalities, it is important to emphasize the necessity of increasing the intake of proteins and polyunsaturated fatty acid-rich foods, as well as vitamins such as A, B6, B9, B12, C, D, and E - It also appears to be positive to increase the consumption of fibers, as this can delay the progression of some chronic respiratory diseases, perhaps through its effects on bowel microbiome , These can be used as an adjunct to an appropriate diet in order to achieve better results.
Supplements should essentially provide an additional amount of calories, but also proteins, amino acids especially those of branched chain , vitamins and minerals , , Liquid supplements with high-caloric content are especially helpful in restoring body weight and skeletal muscle mass in patients with some chronic respiratory disorders However, some recent reviews have not demonstrated clear benefits in others, when there is an already well-balanced diet Regarding protein and amino acid content, the source of the supplement is also important. Those derived from milk or whey appear to be better absorbed and utilized than those obtained from soybean , In the case of CF, pancreatic enzyme replacement is mandatory.
Positive results have not been demonstrated with the administration of these drugs such as megestrol, donabiol or pentoxifylline in underweight chronic respiratory patients Sedentarism, psychological symptoms, skeletal muscle dysfunction and, in some cases, ventilatory limitation, lead to reduced physical activities, which conversely will aggravate these same causes.
This vicious circle should be broken by recommending an increase in outdoor physical activities 11 ; a simple measure that can reduce hospital admissions and improve prognosis and quality of life in COPD - Although it also appears to be able to ameliorate some of these outcomes in other chronic respiratory diseases, more studies are needed , When physical activity is insufficient for obtaining positive results, training programs should be recommended These are able to improve cardiovascular and muscle function, increasing exercise capacity and reducing anxiety and depression symptoms 11 , - In addition, many of the structural and metabolic abnormalities shown by skeletal muscles will erode or even disappear with training , General training has different modalities including endurance exercise training, which is crucial for obtaining an improvement in muscle function and physical capacity 11 , - Strength and resistance training in turn can also be helpful for specifically ameliorating these functional properties of skeletal muscles.
Both the intensity of loads and the pattern of repetitions will determine improvements in strength, endurance or both , An important point is to reach an acceptable nutritional status before starting an intense training program In fact, dietary measures and training potentiate each other, obtaining better results with an appropriate combination 6 , 52 , It is also relevant to initiate training at a moderate level, since high intensity exercise can cause muscle oxidative stress in untrained patients A negative effect that can be easily avoided with progressive increases in the effort requirements until achieving an acceptable level of cardiovascular and muscle conditioning In patients with a very limited exercise capacity, who cannot follow volitional training modalities, it may be necessary to use electric or magnetic stimulation of skeletal muscles - A very interesting and still controversial point is whether it is beneficial, or not, to train patients during or immediately following exacerbations.
These drugs are only necessary in highly selected cases, and most are hormone derivates or releasers, notably those related to androgens or the GH. Some of the former, such as testosterone or nandrolone, are able to enhance the balance between protein synthesis and breakdown, increasing muscle mass 12 , However, they can also produce undesirable side effects, which can nonetheless be reduced with the use of selective androgen receptor modulators SARM As for GH, it also has a powerful anabolic effect, being able to increase body weight in chronic respiratory patients with malnutrition, but unfortunately not demonstrating systematically a clear improvement in muscle function The same appears to be the case for GH secretagogues drugs that promote synthesis or release of GH such as ghrelin, tesamorelin and anamorelin.
Nevertheless, there are some reports showing functional improvements associated with the gain of body and muscle weight with these drugs , Naturally, a good control of the chronic respiratory disease contributes to maintaining nutritional status and muscle function 11 , This is especially important regarding prevention and treatment of exacerbations, when many of the factors leading to nutritional abnormalities and muscle dysfunction become even more accentuated. The therapeutic measures mainly include the use of bronchodilators, vaccines and antibiotics in COPD and bronchiectasis, and the latter drugs and anti-fibrotic therapies in IPF.
Although systemic steroids can be necessary, their dose and the duration of the treatment should be carefully considered. An appropriate and more caloric diet , as well as early mobilization of the patient are also very important.
Series: Lung Biology in Health and Disease (Book ); Hardcover: pages; Publisher: CRC Press; 1 edition (April 18, ); Language: English; ISBN black book lung biology in health disease volume non neoplastic advanced I just were to find, he was. And what had to the one where was including two.
Moreover, more recently it has been suggested that initiating training during or immediately post-exacerbation can partially counterbalance the deleterious effects of these acute episodes , Different substances have been tested so far in order to neutralize local and systemic inflammation and oxidative stress. This is the case of antioxidant substances and antibodies against inflammatory cytokines, their receptors, or some transcription factors.
However, the evidence of positive effects is scarce and some of these therapies have also shown important side effects - These defects can appear together or separately, although they are closely interrelated and share many different etiological factors. Davis AT Collection. Davis PT Collection. Murtagh Collection.
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