Grigoris Stratakos

Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD

It is known that non-cachectic patients with chronic obstructive pulmonary disease (COPD) respond well to pulmonary rehabilitation, but whether cachectic COPD patients are capable of adaptive responses is both important and unknown. 10 cachectic and 19 non-cachectic COPD patients undertook high-intensity cycling training, at the same relative intensity, for 45 min·day−1, 3 days·week−1 for 10 weeks. Before and after rehabilitation vastus lateralis muscle biopsies were analysed morphologically and for the expression of muscle remodelling factors (insulin-like growth factor (IGF)-I, myogenic differentiation factor D (MyoD), tumour necrosis factor (TNF)-α, nuclear factor (NF)-&kgr;B and myostatin) and key components of ubiquitin-mediated proteolytic systems (muscle ring finger protein (MURF)-1 and Atrogin-1). Rehabilitation improved peak work-rate and the 6-min walk distance similarly in non-cachectic (18±3% and 42±13 m, respectively) and cachectic (16±2% and 53±16 m, respectively) patients, but quality of life only improved in non-cachectic COPD. Mean muscle fibre cross-sectional area increased in both groups, but significantly less in cachectic (7±2%) than in non-cachectic (11±2%) patients. Both groups equally decreased the proportion of type IIb fibres and increased muscle capillary/fibre ratio. IGF-I mRNA expression increased in both groups, but IGF-I protein levels increased more in non-cachectic COPD. MyoD was upregulated, whereas myostatin was downregulated at the mRNA and protein level only in non-cachectic patients. Whilst rehabilitation had no effect on TNF-α expression, it decreased the activation of the transcription factor NF-&kgr;B in both groups by the same amount. Atrogin-1 and MURF-1 expression were increased in cachectic COPD, but it was decreased in non-cachectic patients. Cachectic COPD patients partially retain the capacity for peripheral muscle remodelling in response to rehabilitation and are able to increase exercise capacity as much as those without cachexia, even if they exhibit both quantitative and qualitative differences in the type of muscle fibre remodelling in response to exercise training.

Effects of rehabilitative exercise on peripheral muscle TNFα, IL-6, IGF-I and MyoD expression in patients with COPD

Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation. This study investigated whether rehabilitative exercise training decreases the levels of systemic or local muscle inflammation or reverses the abnormalities associated with muscle deconditioning. Methods: Fifteen patients with COPD (mean (SE) forced expiratory volume in 1 s 36 (4)% predicted) undertook high-intensity exercise training 3 days/week for 10 weeks. Before and after the training programme the concentration of tumour necrosis factor &agr; (TNF&agr;), interleukin-6 (IL-6) and C-reactive protein (CRP) in plasma was determined by ELISA, and vastus lateralis mRNA expression of TNF&agr;, IL-6, total insulin-like growth factor-I (IGF-I) and its isoform mechanogrowth factor (MGF) and myogenic differentiation factor D (MyoD) were assessed by real-time PCR. Protein levels of TNF&agr;, IGF-I and MyoD were measured by Western blotting. Results: Rehabilitation improved peak exercise work rate by 10 (2%) (p = 0.004) and mean fibre cross-sectional area from 4061 (254) &mgr;m2 to 4581 (241) &mgr;m2 (p = 0.001). Plasma inflammatory mediators and vastus lateralis expression of TNF&agr; and IL-6 were not significantly modified by training. In contrast, there was a significant increase in mRNA expression of IGF-I (by 67 (22)%; p = 0.044), MGF (by 67 (15)%; p = 0.002) and MyoD (by 116 (30)%; p = 0.001). The increase observed at the mRNA level was also seen at the protein level for IGF-I (by 72 (36)%; p = 0.046) and MyoD (by 67 (21)%; p = 0.012). Conclusions: Pulmonary rehabilitation can induce peripheral muscle adaptations and modifications in factors regulating skeletal muscle hypertrophy and regeneration without decreasing the levels of systemic or local muscle inflammation.

Effect of Pulmonary Rehabilitation on Peripheral Muscle Fiber Remodeling in Patients With COPD in GOLD Stages II to IV

BACKGROUND In most patients with COPD, rehabilitative exercise training partially reverses the morphologic and structural abnormalities of peripheral muscle fibers. However, whether the degree of improvement in muscle fiber morphology and typology with exercise training varies depending on disease severity remains unknown. METHODS Forty-six clinically stable patients with COPD classified by GOLD (Global Initiative for Obstructive Lung Disease) as stage II (n = 14), III (n = 18), and IV (n = 14) completed a 10-week comprehensive pulmonary rehabilitation program consisting of high-intensity exercise three times weekly. RESULTS At baseline, muscle fiber mean cross-sectional area and capillary density did not significantly differ between patients with COPD and healthy control subjects, whereas muscle fiber type I and II proportion was respectively lower (P < .001) and higher (P < .002) in patients with GOLD stage IV compared with healthy subjects and patients with GOLD stages II and III. Exercise training improved, to a comparable degree, functional capacity and the St. George Respiratory Questionnaire health-related quality of life score across all three GOLD stages. Vastus lateralis muscle fiber mean cross-sectional area was increased (P < .001) in all patient groups (stage II: from 4,507 ± 280 μm² to 5,091 ± 271 μm² [14% ± 3%]; stage III: from 3,753 ± 258 μm² to 4,212 ± 268 μm² [14% ± 3%]; stage IV: from 3,961 ± 266 μm² to 4,551 ± 262 μm² [17% ± 5%]), whereas all groups exhibited a comparable reduction (P < .001) in type IIb fiber proportion (stage II: by 6% ± 2%; stage III: by 6% ± 1%; stage IV: by 7% ± 1%) and an increase (P < .001) in capillary to fiber ratio (stage II: from 1.48 ± 0.10 to 1.81 ± 0.10 [23% ± 5%]; stage III: from 1.29 ± 0.06 to 1.56 ± 0.09 [21% ± 5%]; stage IV: from 1.43 ± 0.10 to 1.71 ± 0.13 [18 ± 3%]). The magnitude of changes in the aforementioned variables did not differ across GOLD stages. CONCLUSIONS Functional capacity and morphologic and typologic adaptations to rehabilitation in peripheral muscle fibers were similar across GOLD stages II to IV. Pulmonary rehabilitation should be implemented in patients at all COPD stages.

Effects of rehabilitation on chest wall volume regulation during exercise in COPD patients

In order to investigate underlying mechanisms, the present authors studied the effect of pulmonary rehabilitation on the regulation of total chest wall and compartmental (ribcage, abdominal) volumes during exercise in patients with chronic obstructive pulmonary disease. In total, 20 patients (forced expiratory volume in one second, mean±sem 39±3% predicted) undertook high-intensity exercise 3 days·week-1 for 12 weeks. Before and after rehabilitation, the changes in chest wall (cw) volumes at the end of expiration (EEV) and inspiration (EIV) were computed by optoelectronic plethysmography during incremental exercise to the limit of tolerance (Wpeak). Rehabilitation significantly improved Wpeak (57±7 versus 47±5 W). In the post-rehabilitation period and at identical work rates, significant reductions were observed in minute ventilation (35.1±2.7 versus 38.4±2.7 L·min-1), breathing frequency (26±1 versus 29±1 breaths·min-1) and EEVcw and EIVcw (by 182±79 and 136±37 mL, respectively). Inspiratory reserve volume was significantly increased (by 148±70 mL). Volume reductions were attributed to significant changes in abdominal EEV and EIV (by 163±59 and 125±27 mL, respectively). The improvement in Wpeak was similar in patients who progressively hyperinflated during exercise and those who did not (24 and 26%, respectively). In conclusion, pulmonary rehabilitation lowers chest wall volumes during exercise by decreasing the abdominal volumes. The improvement in exercise capacity following rehabilitation is independent of the pattern of exercise-induced dynamic hyperinflation.

A randomised trial of lung sealant versus medical therapy for advanced emphysema

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events. Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility. Emphysematous lung sealant therapy is highly efficacious in some patients, but benefits bring significant risks http://ow.ly/JJ2vg

Lymphangioleiomyomatosis and Tuberous Sclerosis Complex

Lymphangioleiomyomatosis (LAM) is a rare multisystemic disease of women of child-bearing age and affects mainly the lungs, promoting cystic destruction of lung parenchyma or leading to abdominal tumor formation (e.g., angiomyolipomas, lymphangioleiomyomas). LAM can arise sporadically or in association with tuberous sclerosis complex (TSC), an autosomal inherited syndrome characterized by hamartoma-like tumor growth and pathologic features that are distinct from manifestations of pulmonary LAM. A substantial body of evidence has now been gathered suggesting that the two diseases share a common genetic origin. TSC is caused by mutations in two genes, TSC1 on chromosome 9q34 and TSC2 on 16p13. Both of these genes are tumor suppressor genes encoding hamartin (TSC1) and tuberin (TSC2). Sporadic LAM is correlated with a mutation in the TSC2 gene and tuberin appears to play a central role in the pathogenesis of the disease. A TSC2 loss or mutation leads to disruption of the tuberin-hamartin heteromer and dysregulation of S6K1 activation leading to aberrant cell proliferation seen in LAM disease. The extremely diverse clinical and radiologic features of the disease and the complex therapeutic approach are reviewed in detail. Although new therapeutic agents have been tested, to date no effective treatment has been proposed and the prognosis of patients with LAM remains poor. As long as newer therapeutic agents do not change this picture, lung transplantation remains the last hope for patients with respiratory failure at the advanced stage of the disease.

Throwing performance after resistance training and detraining.

Terzis, G, Stratakos, G, Manta, P, and Georgiadis, G. Throwing performance after resistance training and detraining. J Strength Cond Res 22: 1198-1204, 2008-The purpose of the present study was to investigate the effect of short-term resistance training and detraining on shot put throwing performance. Eleven young healthy subjects with basic shot put skills participated in 14 weeks of resistance training, which was followed by 4 weeks of detraining. Shot put performance in four field tests was measured before (T1) and after (T2) resistance training and after detraining (T3). At the same time points, one repetition maximum (1RM) was measured in squat, bench press, and leg press. Fat-free mass (FFM) was determined with dual x-ray absorptiometry and muscle biopsies obtained from vastus lateralis for the determination of fiber type composition and cross-sectional area (CSA). 1RM strength increased 22-34% (p < 0.01) at T2 and decreased 4-5% (not significantly different) at T3. Shot put performance increased 6-12% (p < 0.05) after training and remained unaltered after detraining. FFM increased at T2 (p < 0.05) but remained unchanged between T2 and T3. Muscle fiber CSA increased 12-18% (p < 0.05) at T2. Type I muscle fiber CSA was not altered after detraining, but type IIa and IIx fiber CSA was reduced 10-12% (p < 0.05). The percentage of type IIx muscle fibers was reduced after training (T1 = 18.7 ± 4, T2 = 10.4 ± 1; p < 0.05), and it was increased at T3 compared with T2 (T3 = 13.7 ± 1; p < 0.05). These results suggest that shot put performance remains unaltered after 4 weeks of complete detraining in moderately resistance-trained subjects. This might be linked to the concomitant reduction of muscle fiber CSA and increase in the percentage of type IIx muscle fibers.

Chest wall volume regulation during exercise in COPD patients with GOLD stages II to IV

The present study investigated how end-expiratory ribcage and abdominal volume regulation during exercise is related to the degree of dynamic chest wall hyperinflation in patients with different spirometric severity of chronic obstructive pulmonary disease (COPD) based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. In total, 42 COPD patients and 11 age-matched healthy subjects were studied during a ramp-incremental cycling test to the limit of tolerance (Wpeak). Volume variations of the chest wall (at end expiration (EEVcw) and end inspiration) and its compartments (ribcage (Vrc) and abdominal (Vab)) were computed by optoelectronic plethysmography. At Wpeak, only patients in GOLD stages III and IV exhibited a significant increase in EEVcw (increase of 454±509 and 562±363 mL, respectively). These patients did not significantly reduce end-expiratory Vab, whereas patients in GOLD stage II resembled healthy subjects with significantly reduced end-expiratory Vab (decrease of 287±350 mL). In patients, the greater the increase in EEVcw at Wpeak, the smaller the reductions in end-expiratory Vab and the greater the increase in end-expiratory Vrc. In chronic obstructive pulmonary disease patients with different spirometric disease severity, greater degrees of exercise-induced dynamic chest wall hyperinflation were accompanied by lower degrees of end-expiratory abdominal volume displacement and larger increases in end-expiratory ribcage volume.

Effects of interval-load versus constant-load training on the BODE index in COPD patients

The BODE index is frequently used to assess functional capacity in patients with COPD. The aim of this study was to investigate the effectiveness of interval-load training (ILT) to improve the BODE index in comparison to the commonly implemented constant-load training (CLT). Forty-two patients with COPD [FEV(1): (mean+/-SEM) 42+/-3% predicted] were randomly allocated to either ILT (n=21) or CLT (n=21). The training program consisted of cycling exercise 3 days/week for 10 weeks. Patients assigned to ILT exercised at a mean intensity of 126+/-4% of baseline peak work rate (Wpeak) with 30-s work periods alternated with 30-s rest periods for 45 min per day, whereas patients allocated to CLT exercised at a mean intensity of 76+/-5% of baseline Wpeak for 30 min per day. The BODE index and its components: body mass index, FEV(1), MMRC dyspnea score and the 6-min walk test (6-MWT) as well as cycling Wpeak were assessed before and after both exercise training regimes. Both ILT and CLT significantly (p<0.001) decreased the BODE index (from 4.8+/-0.5 to 4.0+/-0.5 units and from 4.4+/-0.5 to 3.8+/-0.5 units, respectively). In addition, both ILT and CLT significantly decreased the MMRC dyspnea score by 0.4+/-0.1 units and increased the 6-MWT (by 52+/-16 and 44+/-12 m, respectively) as well as cycling Wpeak (by 14+/-2 and 10+/-2W, respectively). The magnitude of these changes was not significantly different between ILT and CLT. Consequently, ILT is equally effective to CLT in terms of improving the BODE index in patients with COPD and as such it may constitute an alternative rehabilitative modality in COPD.

Drug Eluting Stents for Malignant Airway Obstruction: A Critical Review of the Literature

Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin C and sirolimus have been observed to assist a successful stent placement by reducing granuloma tissue formation. Additionally, these drugs enhance the normal tissue ability against cancer cell infiltration. In this mini review we will concentrate on mitomycin C and sirolimus and their use in stent placement.