Progressive Resistance Training of the Extensor Muscle of the Thigh in COPD-patients Hospitalized With an Exacerbation
Progressive Resistance Training of the Extensor Muscle of the Thigh in COPD-patients Hospitalized With an Exacerbation
We want to test the hypothesis, that resistance training by the use of weigth cuffs on the
 angle can prevent loss or improve the strength of the quadriceps muscle in COPD patients
 admitted to hospital due to an exacerbation. The training is started at day one of admittance
 and the strength of the quadriceps is measured by a portable dynamometer.
Background Chronic obstructive pulmonary disease (COPD) is one of the most costly chronic
 diseases (1). In Denmark it can be estimated that approximately 400.000 people suffers from
 COPD amounting to about 15% of the adult population. COPD causes 10.000 visits to the
 emergency room, approx. 25.000 acute admissions to hospital and 3.500 deaths a year. The
 disease costs approx 2 billion Danish croners (400 million dollars) a year. Hospital
 admissions due to exacerbations adds to the most costly part of the disease burden to
 society. COPD is one of the few chronic diseases still on the rise (1).

 COPD is characterized by an accelerated decline in lung function. Most of the patients with
 severe degree of COPD suffer from recurrent acute deterioration named exacerbations. An
 exacerbation is defined as a deterioration in symptoms including shortness of breath and
 sputum production leading to a chance in medical treatment. Frequent exacerbations are
 associated with an extra high rate of decline in lung function and a strongly negative impact
 on the quality of life. The disease progression is followed by a gradual loss in muscle mass
 and strength (3).

 Admission to hospital has well known effects on maximal oxygen consumption and a reduction in
 the physical condition leads to a more severe degree of shortness of breath during physical
 activity (4). Just a few days in bed is followed by an important loss of muscle mass and
 strength. Immobilization causes a decrease in metabolism and a loss of active motor units and
 a reduced ability to activate the resting motor units. This has a greater negative impact on
 the strength in the extensors that are engaged in maintaining the upright position than other
 muscle groups. In keeping with this, the loss of muscle strength occurs at twice as high a
 rate in muscles of the lower limb than in those of the upper limb (5). This leads to an
 increased production of lactic acid and corresponding muscle fatique (6). Muscles engaged in
 knee extension loose strength at the highest rate during immobilization. This loss has great
 impact on the activities of daily life such as getting out of bed, rising from a chair and
 climbing stairs. Even though the patients regain their premorbide lung function and their
 symptoms improve to the "normal" level usually within 6 weeks, they do not reach their
 habitual level of physical activity as expressed by the 6MWT (7). Admittance due to
 exacerbations is followed by muscle wasting and prolonged inactivity, leading to an increased
 risk of recurrent exacerbations.

 Physical training of the muscles is the most efficient treatment to maintain or increase
 muscle strength to prevent muscle wasting during immobilization. Since most of the decline in
 muscle strength occurs during the first days of bed rest - 3-4% per day - and most pronounced
 in the muscles of the lower limb, there is god reason for early intervention with physical
 training of the extensors of the lower limb, the earlier after admittance, the better.

 There is solid evidence for a positive effect of training of clinically stable COPD patients.
 Only two studies have investigated the effect of training during admittance for an acute
 exacerbation (8) In the study by Troosters, the training consisted of 3 sets of 8 repetitions
 amounting to 70% of 1 repetition maximum (1RM: repetitions maximum: the maximal weight that
 can be handled only one time). The subjects had an FEV1 of 40 ± 12 % of predicted, and were
 trained by the use of a knee extension machine. We do not know the exact exclusion criteria
 of the study - did they include patients who were unable to move from the bed to the knee
 extension machine? Did the physiotherapists handled the most severely diseased patients
 differently? Moreover, it would be more general applicable, if the training could be
 performed with a less demanding and expensive equipment than a knee extension machine.
 Accordingly, there is a need for at study with a more detailed description of the training
 procedure, using a simple, low cost training device, that is applicable to many centers and
 hospital units.

 Most patients suffering from a severe degree of COPD (GOLD III and IV) (3)will experience
 severe shortness of breath leading to exhaustion even after very low level activities.
 Unilateral resistance training of the quadriceps by the use of wrist weights is low cost, low
 technology.

 The pilot study at our department of pulmonary medicine, Frederikssund Hospital, including 8
 severely diseased COPD patients, trained by wrist weights on average for 5 days, showed that
 all patients improved their muscle strength - amounting to an average of 50%.

 The study showed that progressive lower limb muscle exercise was possible even in the most
 severely disabled patients on home oxygen. We do not know if the surprisingly high degree of
 improvement should be ascribed to the training or other factors. Accordingly, we want to
 perform a randomized controlled single blinded study to clarify if progressive resistance
 training with wrist weights can improve the strength of the large extensor muscle of the
 lower limb to a degree that will translate into improved physical ability after discharge
 from hospital.

 Randomizing The investigation is designed as a randomized, controlled, single blinded study.
 Patients who fulfill the inclusion criteria and none of the exclusion criteria are invited to
 participate in the study. After an initial evaluation and testing the patients are randomized
 to either standard pulmonary physiotherapy and physical training (intervention group) or
 standard physiotherapy without training (control group). The list of randomization is based
 on a computer program. Numbers of randomization are kept in 70 closed envelopes. The content
 of the envelope is disclosed only after inclusion, initial evaluation and testing. The
 envelopes are numbered on the outside (a consecutive line of numbers different from the
 numbers of randomization) and kept by a secretary and released in the order of outside
 number.

 Tests at inclusion and after 6 weeks will be performed by physiotherapists blinded to the
 randomization. It is impossible to blind the physicians, nurses and physiotherapists at the
 pulmonary ward.

 Security and Ethics Based on the current evidence, the patients are not exposed to any kind
 of risk, except that a slight degree of muscle soreness may occur following the first few
 days of physical training. The study is not blinded to the physiotherapists who perform the
 training, and if any problem related to training should occur, it will be easily addressed.

 The present study aims at progressive physical training with cheap equipment which is easy to
 handle for both the physiotherapists and the patients with minimal risk to the patients. This
 adds to the importance of the study.

 The control group will be treated according to usual therapeutic guidelines. The study is
 reported to the local ethical committee. The patients are covered by patient insurance of
 Frederikssund Hospital.

 Registration of data and informed consent Data evaluation agrees to the technical demands
 made by the Danish Data Protection Agency The patients are familiar with all collected data,
 and information about this included in the informed consent.

 All data of the study will be kept in a separate locked container in a locked room. Only the
 principal investigator has access to the room and container. Data will be stores in excel,
 where every patient has a unique number and all date from that particular patient is stored
 under this number. The security container is obtained for the specific purpose of the study
 and is in accordance with the procedures of the local region regarding login on the internet.

 The patients will be contacted by the principal investigator or another member of the staff
 adequately trained for the study within 24 hours of admittance to the pulmonary ward of
 Frederikssund Hospital.

 The patients will receive oral information and information in writing about the study the day
 of admittance, about their rights as voluntaries in a scientific study in the field of health
 science. The patient will be informed about the nature of the study according to the
 guidelines of The Danish Council of Ethics. The oral information is guided by the information
 in writing, where every aspect of the study is explained in detail to the patient. Informed
 consent is obtained the day after information after a minimum of 24 hours of reconsideration.
 The patient can decide to withdraw from the study at any time during the investigation. The
 investigators can also decide that a patient should be withdrawn from the study and the
 reason for exclusion should be documented in the research files.

 Statistics The primary aim of the study is to compare the strength of the extensor of the
 thigh of the intervention group with that of the control group by an isometric contraction
 test.

 Calculations have showed that the need for 35 subjects in each group to be able to reveal a
 difference in strength of at least 30%, with a limit of statistical significance of 5% and a
 power of 80%. The power calculation is based on the expected change in extension strength
 from the start of the study to discharge where it is not expected that the control group will
 improve in strength. .

 The applied statistical analyses (by SPSS) will be repeated measures (ANOVA) to determine a
 systematic difference between muscle strenght with or without quadriceps training.

 Measurements All participants are tested latest on day one after admittance, at discharge
 from hospital and on an outpatient basis 6 weeks later. The day of admittance is denoted as
 day 0. The 6 weeks follow up are chosen due to the belief that most COPD patients are
 clinically stable 6 weeks after an exacerbation.

 Economy and Time schedule The study is started up by the persons responsible for the
 investigation. The study is not yet fully financed. We are planning to apply for additional
 finalcial support. None of the foundations will have any connection to the drug industry and
 none of the possible supporters will have any impact on the results, their interpretation or
 publication.

 The study will start in autumn 2012 and finished when all 70 COPD patients are included and
 followed up, hopefully finished autumn 2013.

 The results of the study both positive, negative and inconclusive will be reported in an
 international journal of pulmonary medicine. The results will be presented at relevant
 congresses both in Denmark and abroad

 References

 (1) Juel K, Døssing M. KOL i Danmark: sygdommen der hver dag koster 10 danskere livet. Kbh.:
 Statens Institut for Folkesundhed; 2003.

 (3) GOLD- Guidelines. Global Strategy for the Diagnosis, Management and Prevention of COPD,
 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011.. Available at:
 www.goldcopd.org. Accessed 26.06.12.

 (4) Bernard S, LeBlanc P, Whittom F, Carrier G, Jobin J, Belleau R, et al. Peripheral muscle
 weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med
 1998 Aug;158(2):629-634.

 (5) Bloomfield SA. Changes in musculoskeletal structure and function with prolonged bed rest.
 Med Sci Sports Exerc 1997 Feb;29(2):197-206.

 (6) Steiner MC, Evans R, Deacon SJ, Singh SJ, Patel P, Fox J, et al. Adenine nucleotide loss
 in the skeletal muscles during exercise in chronic obstructive pulmonary disease. Thorax 2005
 Nov;60(11):932-936.

 (7) Pitta F, Troosters T, Probst VS, Spruit MA, Decramer M, Gosselink R. Physical activity
 and hospitalization for exacerbation of COPD. Chest 2006 Mar;129(3):536-544.

 (8) Troosters T, Probst VS, Crul T, Pitta F, Gayan-Ramirez G, Decramer M, et al. Resistance
 training prevents deterioration in quadriceps muscle function during acute exacerbations of
 chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010 May
 15;181(10):1072-1077
Inclusion Criteria:

 -  Have a primary diagnosis of COPD

 -  Be admitted to the pulmonary ward due to an exacerbation in COPD

 -  Provide informed consent to participation in the study

 -  Be able to maintain an upright position on a chair

 -  Be able to be guided to training and understand instructions for participating.

 Exclusion Criteria:

 -  Patients suffering from diseases that prevents the use of wrist weights such as

 -  Deep venous thrombosis (DVT)

 -  Erysipelas

 -  Painfull edema of the limbs And

 -  Lack of ability to walk, habitually

 -  Already participating in COPD rehabilitation program

 -  Predicted hospital stay of less than tree days as predicted by a • pulmonary
 physician

 -  Patients admitted Friday night or Saturday morning cannot be stared up within 24
 hours of admittance