Impaired Respiratory Muscle Function Research Articles

Efficacy of chest expansion resistance exercise on respiratory function, trunk control and dynamic balance in patients with chronic stroke: A Comparative study.

BackgroundMotor impairments caused by stroke result in impaired diaphragmatic and respiratory muscle function, changes in thoracic biomechanics on the hemiparetic side ultimately resulting in decreased efficiency of lung ventilation. This study aimed to examine the efficacy of chest expansion resistance exercise (CERE) on respiratory function, trunk control ability, and balance in patients with chronic stoke. Following a purposive sampling, thirty-five patients with chronic stroke were randomly allocated into two groups, i.e., the experimental group receiving CERE with conventional therapy and the control group receiving conventional therapy alone. Both the groups received therapy four times per week for a period of four weeks (total 16 sessions). Following assessments were done before and after treatment in both the groups: chest expansion ( axillary, nipple, xiphisternal levels) using measure tape, respiratory muscle strength using micro-respiratory pressure meter, trunk control using the Trunk Impairment Scale, and balance using mini-Balance Evaluation Systems Test.ResultsBoth groups had 17 participants each (n = 34, drop-outs = 1) consisting of 12 males and 5 females having a mean age of 56.5 ± 12.98 years and 59.7 ± 10.2 years, respectively. Intra-group analysis showed a statistically significant increase in mean values of chest expansion, respiratory muscle strength, trunk control ability, and balance in the experimental group whereas the control group showed improvement only in trunk control ability and balance. Inter-group comparison revealed a better improvement in all the outcome variables in experimental group compared to the control group.ConclusionsBased on these results, this study proved that CERE was more effective in improving respiratory function, trunk control, and balance in patients with chronic stroke.

Epigenetic silencing by early-life hypoxic stress programmes respiratory motor control.

Epigenetic silencing by early-life hypoxic stress programmes respiratory motor control.

Derangements of amino acids in cachectic skeletal muscle are caused by mitochondrial dysfunction.

BackgroundCachexia is the direct cause of at least 20% of cancer‐associated deaths. Muscle wasting in skeletal muscle results in weakness, immobility, and death secondary to impaired respiratory muscle function. Muscle proteins are massively degraded in cachexia; nevertheless, the molecular mechanisms related to this process are poorly understood. Previous studies have reported conflicting results regarding the amino acid abundances in cachectic skeletal muscle tissues. There is a clear need to identify the molecular processes of muscle metabolism in the context of cachexia, especially how different types of molecules are involved in the muscle wasting process.MethodsNew in situ ‐omics techniques were used to produce a more comprehensive picture of amino acid metabolism in cachectic muscles by determining the quantities of amino acids, proteins, and cellular metabolites. Using matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry imaging, we determined the in situ concentrations of amino acids and proteins, as well as energy and other cellular metabolites, in skeletal muscle tissues from genetic mouse cancer models (n = 21) and from patients with cancer (n = 6). Combined results from three individual MALDI mass spectrometry imaging methods were obtained and interpreted. Immunohistochemistry staining for mitochondrial proteins and myosin heavy chain expression, digital image analysis, and transmission electron microscopy complemented the MALDI mass spectrometry imaging results.ResultsMetabolic derangements in cachectic mouse muscle tissues were detected, with significantly increased quantities of lysine, arginine, proline, and tyrosine (P = 0.0037, P = 0.0048, P = 0.0430, and P = 0.0357, respectively) and significantly reduced quantities of glutamate and aspartate (P = 0.0008 and P = 0.0124). Human skeletal muscle tissues revealed similar tendencies. A majority of altered amino acids were released by the breakdown of proteins involved in oxidative phosphorylation. Decreased energy charge was observed in cachectic muscle tissues (P = 0.0101), which was related to the breakdown of specific proteins. Additionally, expression of the cationic amino acid transporter CAT1 was significantly decreased in the mitochondria of cachectic mouse muscles (P = 0.0133); this decrease may play an important role in the alterations of cationic amino acid metabolism and decreased quantity of glutamate observed in cachexia.ConclusionsOur results suggest that mitochondrial dysfunction has a substantial influence on amino acid metabolism in cachectic skeletal muscles, which appears to be triggered by diminished CAT1 expression, as well as the degradation of mitochondrial proteins. These findings provide new insights into the pathobiochemistry of muscle wasting.

Hypoxia induced mitogenic factor (HIMF) triggers angiogenesis by increasing interleukin-18 production in myoblasts

Inflammatory myopathy is a rare autoimmune muscle disorder. Treatment typically focuses on skeletal muscle weakness or inflammation within muscle, as well as complications of respiratory failure secondary to respiratory muscle weakness. Impaired respiratory muscle function contributes to increased dyspnea and reduced exercise capacity in pulmonary hypertension (PH), a debilitating condition that has few treatment options. The initiation and progression of PH is associated with inflammation and inflammatory cell recruitment and it is established that hypoxia-induced mitogenic factor (HIMF, also known as resistin-like molecule α), activates macrophages in PH. However, the relationship between HIMF and inflammatory myoblasts remains unclear. This study investigated the signaling pathway involved in interleukin-18 (IL-18) expression and its relationship with HIMF in cultured myoblasts. We found that HIMF increased IL-18 production in myoblasts and that secreted IL-18 promoted tube formation of the endothelial progenitor cells. We used the mouse xenograft model and the chick chorioallantoic membrane assay to further explore the role of HIMF in inflammatory myoblasts and angiogenesis in vivo. Thus, our study focused on the mechanism by which HIMF mediates IL-18 expression in myoblasts through angiogenesis in vitro and in vivo. Our findings provide an insight into HIMF functioning in inflammatory myoblasts.

Effects of inspiratory muscle exercise in the pulmonary function, autonomic modulation, and hemodynamic variables in older women with metabolic syndrome.

The aim of the present study was to investigate the effects of inspiratory muscle exercise (IME) on metabolic and hemodynamic parameters, cardiac autonomic modulation and respiratory function of older women with metabolic syndrome (MS). For this, sixteen older women with MS and 12 aged-matched controls participated of the present study. Two days before and 2 days after the main experiment, fasting blood samples (i.e., total cholesterol, triglycerides and blood glucose), cardiac autonomic modulation (i.e., heart rate variability), and respiratory muscle function were obtained and evaluated. The sessions of physical exercise was based on a IME, which was performed during 7 days. Each session of IME was performed during 20 min, at 30% of maximal static inspiratory pressure. In the results, MS group presented higher levels of triglycerides, blood glucose, and systolic blood pressure when compared to control group. IME was not able to change these variables. However, although MS group showed impaired respiratory muscle strength and function, as well as cardiac autonomic modulation, IME was able to improve these parameters. Thus, the data showed that seven days of IME are capable to improve respiratory function and cardiac autonomic modulation of older women with MS. These results indicate that IME can be a profitable therapy to counteracting the clinical markers of MS, once repeated sessions of acute IME can cause chronical alterations on respiratory function and cardiac autonomic modulation.

Targeting IL‐6 and CRFR2 Improves Diaphragm Muscle Function and Restores Ventilation in Mdx Mice

Duchenne muscular dystrophy (DMD) is a genetic disease caused by a mutation in the dystrophin gene, leading to the absence of the structural protein ‐ dystrophin. Patients have severe muscle weakness and die prematurely due to respiratory and cardiac failure. The mdx mouse model of DMD shows evidence of reduced normoxic ventilation and impaired respiratory muscle function at 8 weeks of age.6 week old mdx (C57BL/10ScSn‐Dmdmdx/J; n=24) and wild‐type (WT; C57BL/10ScSn; n=23) mice received either saline (0.9% w/v) or a co‐treatment of neutralizing IL‐6 receptor antibodies (xIL‐6R; 0.2 mg/kg) and corticotrophin releasing factor receptor 2 agonist (Urocortin‐2; 30μg/kg). Animals received 6 subcutaneous injections over 2 weeks. Following this, ventilation was assessed in animals by use of whole body plethysmography. Diaphragm muscle contractile function was examined ex vivo. Muscle fibre nucleation and inflammatory cell infiltration were examined by haematoxylin and eosin staining. Immunofluorescence was used to visualize collagen deposition in muscle. Fibre type distribution and cross‐sectional area (CSA) was determined by myosin heavy chain (MHC) immunofluorescence. Values are reported as mean±SD and data were statistically compared by two‐way ANOVA with Bonferroni post‐hoc test.Peak specific force (Fmax) was significantly reduced in mdx (8.7±2.8 N/cm2) compared with WT (19.3±5.5). Co‐treatment increased Fmax for mdx (15.6±2.7) towards WT values. Minute ventilation was significantly reduced in mdx (0.9±0.2 ml/min/g) compared with WT (1.2±0.2). Co‐treatment restored ventilation in mdx (1.3±0.2) to values equivalent to WT. The percentage of centrally‐nucleated muscle fibres was significantly increased in mdx (15.9±2.8%) compared with WT (0.8±0.5%). In addition, the areal density of inflammatory cell infiltrates was significantly increased (6.6±1.5% vs. 2.2±0.7%; mdx vs. WT). Similarly, percentage of collagen deposition was significantly increased in mdx compared with WT (12.2±1.7% vs. 7.0 ± 2.2%). All indices were unaffected by drug co‐treatment. Altered fibre type distribution was apparent in the mdx diaphragm muscle. The areal and numerical density of MHCIIa fibres was significantly increased, whereas MHCIIx and IIb fibres were significantly decreased compared with WT. Differences in fibre type complement were ameliorated by drug co‐treatment.Co‐treatment restored ventilation in mdx and had a positive inotropic effect, increasing mechanical force in dystrophic diaphragm muscle. Co‐treatment restored fibre distribution in mdx but did not affect the infiltration of inflammatory cells, the proportion of fibres with evidence of central nucleation and enhanced collagen type I deposition. Preservation of MHCIIx fibres may underpin, at least in part, recovery of breathing and force production in the co‐treated mdx mice. These data may have implications for the development of pharmacotherapies for DMD with relevance to respiratory muscle performance and ventilatory status.Support or Funding InformationDepartment of Physiology (UCC) and Muscular Dystrophy Ireland. The IL‐6R antibodies were kindly gifted by Chugai Pharmaceuticals, Japan.

Targeting Heat Shock Proteins Mitigates Ventilator Induced Diaphragm Muscle Dysfunction in an Age-Dependent Manner.

Intensive care unit (ICU) patients are often overtly subjected to mechanical ventilation and immobilization, which leads to impaired limb and respiratory muscle function. The latter, termed ventilator-induced diaphragm dysfunction (VIDD) has recently been related to compromised heat shock protein (Hsp) activation. The administration of a pharmacological drug BGP-15 acting as a Hsp chaperone co-inducer has been found to partially alleviate VIDD in young rats. Considering that the mean age in the ICU is increasing, we aimed to explore whether the beneficial functional effects are also present in old rats. For that, we exposed young (7–8 months) and old (28–32 months) rats to 5-day controlled mechanical ventilation and immobilization with or without systemic BGP-15 administration. We then dissected diaphragm muscles, membrane–permeabilized bundles and evaluated the contractile function at single fiber level. Results confirmed that administration of BGP-15 restored the force-generating capacity of isolated muscle cells from young rats in conjunction with an increased expression of Hsp72. On the other hand, our results highlighted that old rats did not positively respond to the BGP-15 treatment. Therefore, it is of crucial importance to comprehend in more depth the effect of VIDD on diaphragm function and ascertain any further age-related differences.

Empfehlungen der Deutschen Atemwegsliga zur Messung der Atemmuskelfunktion

Based on the tremendous impact of impaired respiratory muscle function, tests on their function play a significant role in respiratory and intensive care medicine. Besides differential diagnosing e.g. during prolonged weaning and quantification of impaired respiratory muscle function, e.g. in COPD, neuro-muscular diseases or ventilator-induced diaphragmatic dysfunction, those tests qualify for follow-up assessment, e.g. phrenic nerve lesions or specific respiratory muscle training. In general, (simple) volitional and (complex) non-volitional tests are available. Volitional tests aim at screening for potential respiratory muscle impairment, while non-volitional tests - including ultrasound application - are used to further specify low values assessed by volitional tests and to assess complex clinical conditions (e.g. intubated, sedated patients). Several tests are complementary or additive to each other. Complete assessment for respiratory muscle function, therefore, frequently requires the combination of different test regimes. The current recommendations include in-depth description and practical guidelines for the different tests and approaches to assess respiratory muscle function.

The Combination of Exercise and Respiratory Training Improves Respiratory Muscle Function in Pulmonary Hypertension

Increased dyspnea and reduced exercise capacity in pulmonary arterial hypertension (PAH) can be partly attributed to impaired respiratory muscle function. This prospective study was designed to assess the impact of exercise and respiratory training on respiratory muscle strength and 6-min walking distance (6MWD) in PAH patients. Patients with invasively confirmed PAH underwent 3weeks of in-hospital exercise and respiratory training, which was continued at home for another 12weeks. Medication remained constant during the study period. Blinded observers assessed efficacy parameters at baseline (I) and after 3 (II) and 15weeks (III). Respiratory muscle function was assessed by twitch mouth pressure (TwPmo) during nonvolitional supramaximal magnetic phrenic nerve stimulation. Seven PAH patients (4 women; mean pulmonary artery pressure 45±11mmHg, median WHO functional class 3.1±0.4, idiopathic/associated PAH n=5/2) were included. The training program was feasible and well tolerated by all patients with excellent compliance. TwPmo was I: 0.86±0.37kPa, II: 1.04±0.29kPa, and III: 1.27±0.44kPa, respectively. 6MWD was I: 417±51m, II: 509±39m, and III: 498±39m, respectively. Both TwPmo (+0.41±0.34kPa, +56±39%) and 6MWD (+81±30m, +20±9%) increased significantly in the period between baseline and the final assessment (pairwise comparison: p=0.012/<0.001; RM-ANOVA considering I, II, III: p=0.037/<0.001). Exercise and respiratory training as an adjunct to medical therapy may be effective in patients with PAH to improve respiratory muscle strength and exercise capacity. Future, randomized, controlled trials should be carried out to further investigate these findings.

ChronicPseudomonas aeruginosaInfection and Respiratory Muscle Impairment in Cystic Fibrosis

Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is associated with increased morbidity. Chronic infection can cause limb and respiratory muscle compromise. Respiratory muscle function can be assessed via maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and the pressure-time index of the respiratory muscles (PTImus). We studied the effect of chronic P. aeruginosa infection on respiratory muscle function in patients with CF. This cross-sectional study assessed PImax, PEmax, PTImus, FEV1, FVC, maximum expiratory flow during the middle half of the FVC maneuver, body mass index, and upper arm muscle area in 122 subjects with CF, in 4 subgroups matched for age and sex at different stages of P. aeruginosa infection, according to the Leeds criteria. We compared respiratory muscle function in the subgroups according to P. aeruginosa infection state. Median PImax was significantly lower in CF subjects with chronic P. aeruginosa infection (PImax = 62 cm H2O), compared to subjects who were never infected (PImax = 86 cm H2O, P = .02), free of infection (PImax = 74 cm H2O, P = .01), or intermittently infected (PImax = 72 cm H2O, P = .02). Median PTImus was significantly increased in CF subjects with chronic P. aeruginosa infection (PTImus = .142), compared to subjects who were free of infection (PTImus = .102, P = .006). Median upper-arm muscle area was significantly lower in CF subjects with chronic P. aeruginosa infection (upper-arm muscle area = 2,219 mm(2)), compared to subjects who were never infected (2,754 mm(2), P = .03), free of infection (2,678 mm(2), P = .01), or intermittently infected (2,603 mm(2), P = .04). Multivariate logistic regression revealed P. aeruginosa state of infection as a significant determinant of PTImus (P = .03) independently of sex, upper-arm muscle area, and FEV1. CF subjects with chronic P. aeruginosa infection exhibited impaired respiratory muscle function and decreased inspiratory muscle strength, and chronic P. aeruginosa infection independently impacts respiratory muscle function in subjects with CF.

Low-dose Sugammadex Reversal

Low-dose Sugammadex Reversal

Low Exercise Tolerance Correlates With Reduced Inspiratory Capacity and Respiratory Muscle Function in Recipients With Advanced Chronic Lung Allograft Dysfunction

Advanced chronic lung allograft dysfunction limits survival after lung transplantation. We hypothesize that patients with chronic lung allograft dysfunction can be subdivided by exercise tolerance in two groups, and quality of life (QOL) and survival differ between the groups. A single-center, cross-sectional, partly prospective, study was performed in our outpatient clinic between July and November 2011, including all patients with a forced expiratory volume in 1 s <50% baseline. Respiratory parameters, 6-min walk test, and QOL were measured. Patients with low exercise capacity were defined as 6-min walk test <50% predicted or use of rollator or wheelchair. Fifty-two patients consented to participating in the study and 22 demonstrated low exercise capacity. These patients had pathologic respiratory muscle function (P=0.005) and decreased inspiratory capacity (IC; P=0.001). QOL was significantly reduced. Multivariate analysis proved that low IC (hazard ratio, 17.9; 95% confidence interval, 2.8-111; P=0.002) and increased P0.1/Pimax (hazard ratio, 7.1; 95% confidence interval, 1.4-35.8; P=0.016) were independently associated with decrease exercise capacity. Heterogeneity of patients with advanced lung allograft dysfunction regarding exercise tolerance might result from altered IC and impaired respiratory muscle function.

Respiratory muscle function in interstitial lung disease

Interstitial lung diseases limit daily activities, impair quality of life and result in (exertional) dyspnoea. This has mainly been attributed to a decline in lung function and impaired gas exchange. However, the contribution of respiratory muscle dysfunction to these limitations remains to be conclusively investigated. Interstitial lung disease patients and matched controls performed body plethysmography, a standardised 6-min walk test, volitional tests (respiratory drive (P0.1), global maximal inspiratory mouth occlusion pressure (PImax), sniff nasal pressure (SnPna) and inspiratory muscle load) and nonvolitional tests on respiratory muscle function and strength (twitch mouth and transdiaphragmatic pressure during bilateral magnetic phrenic nerve stimulation (TwPmo and TwPdi)). 25 patients and 24 controls were included in the study. PImax and SnPna remained unaltered (both p>0.05), whereas P0.1 and the load on the inspiratory muscles were higher (both p<0.05) in interstitial lung disease patients compared with controls. TwPmo and TwPdi were lower in interstitial lung disease patients (mean±sd TwPmo 0.86±0.4 versus 1.32±0.4, p<0.001; TwPdi 1.34±0.6 versus 1.88±0.5, p=0.022). Diaphragmatic force generation seems to be impaired in this cohort of interstitial lung disease patients while global respiratory muscle strength remains preserved. Central respiratory drive and the load imposed on the inspiratory muscles are increased. Whether impaired respiratory muscle function impacts morbidity and mortality in interstitial lung disease patients needs to be investigated in future studies.

Residual Neuromuscular Blockade Affects Postoperative Pulmonary Function

Residual neuromuscular blockade (RNMB) is known to be associated with respiratory complications in the postoperative period after muscle relaxant usage. The authors hypothesized that RNMB causes reductions in pulmonary function test (PFT) parameters in the immediate postoperative period. An open-label prospective randomized cohort study was conducted comparing reductions in PFT parameters due to RNMB among different neuromuscular blocking agents. One hundred and fifty patients were randomized to receive vecuronium, atracurium, or rocuronium. After reversal of neuromuscular blockade and extubation, train-of-four ratio was measured every 5 min until the train-of-four ratio of 0.9 or greater was attained. PFTs were performed preoperatively and postoperatively when the patients were willing and fit. The train-of-four ratio, measured at PFT, was used to classify patients into "RNMB absent" and "RNMB present." RNMB was defined as a train-of-four ratio less than 0.9. Thirty-nine patients had RNMB at the time of performing PFT. There was no statistically significant difference in the postoperative reductions in PFT parameters in patients with RNMB among different neuromuscular blocking agents. Patients were regrouped as RNMB absent and RNMB present, irrespective of neuromuscular blocking agents. Postoperative PFT values for the RNMB-absent and RNMB-present groups were 62% and 49% of baseline forced vital capacity and 47% and 38% of baseline peak expiratory flow of the baseline, respectively. Postoperative forced vital capacity and peak expiratory flow values of RNMB-present patients were lower by 13% and 9% in absolute terms (P<0.008) and 21% and 19% in relative terms, respectively, compared with RNMB-absent patients. RNMB results in reductions in forced vital capacity and peak expiratory flow in the immediate postoperative period indicating impaired respiratory muscle function.

Respiratory muscle function in patients with cystic fibrosis

Respiratory muscle function in patients with cystic fibrosis (CF) can be assessed by measurement of maximal inspiratory pressure (Pimax ), maximal expiratory pressure (Pemax ), and pressure-time index of the respiratory muscles (PTImus ). We investigated the differences in maximal respiratory pressures and PTImus between CF patients with no gross hyperinflation and healthy controls and described the effects of pulmonary function and nutrition impairment on respiratory muscle function in this group of CF patients. Forced expiratory volume in 1 sec (FEV1 ), forced vital capacity (FVC) and maximal expiratory flow between 25% and 75% of VC (MEF25-75 ), body mass index (BMI), upper arm muscle area (UAMA), Pimax , Pemax , and PTImus were assessed in 140 CF patients and in a control group of 140 healthy subjects matched for age and gender. Median Pimax and Pemax were significantly lower in CF patients compared to the controls [Pimax = 74 (57-94) in CF vs. 84 (66-102) in controls, P = 0.009], [Pemax = 71 (50-95) in CF vs. 84 (66-102) in controls, P < 0.001]. Median PTImus in CF patients compared to controls was significantly increased [PTImus = 0.110 (0.076-0.160) in CF vs. 0.094 (0.070-0.137) in controls, P = 0.049] and it was significantly higher in CF patients with impaired pulmonary function. In CF patients, PTImus was significantly negatively related to upper arm muscle area (r = 0.184, P = 0.031). These findings suggest that CF patients with no severe lung disease compared to healthy subjects exhibit impaired respiratory muscle function, while CF patients with impaired pulmonary function and nutrition indices exhibit higher PTImus values.

Effect of acetazolamide on respiratory muscle fatigue in humans

Previous studies have demonstrated that carbonic anhydrase inhibition with acetazolamide reduces exercise capacity. The mechanism responsible for this early fatigue is unclear, but may be partly mediated by impaired respiratory muscle function. Inspiratory muscle strength and endurance were assessed in seven healthy men (age 28±5yrs, ±SD) by measuring maximal inspiratory pressure (MIP) and time to task failure during a constant-load breathing test (CLBT), respectively, under control (CON) and acetazolamide (ACZ; 500mg/8h po for 3 days) conditions that were separated by two weeks and randomized between subjects. In addition, MIP was measured before and after moderate-intensity cycling exercise to fatigue while pulmonary gas exchange, plasma pH, and ventilation were measured during exercise. ACZ did not alter pulmonary function (FVC, FEV1, MVV) or MIP measured at rest (CON, −157±47 vs. ACZ, −154±45cmH2O, p>0.05), but decreased time to task failure during the CLBT (CON, 1340±820 vs. ACZ, 698±434s; p=0.01). Exercise duration during cycling exercise was reduced (p=0.003) with ACZ (1090±254s) compared to CON (1944±532s) in the presence of a significantly lower plasma pH and higher ventilation compared to control (p<0.05). Compared to resting values, MIP was reduced (p=0.03) in ACZ but not CON at exhaustion. In conclusion, carbonic anhydrase inhibition with ACZ is associated with impaired respiratory muscle function at rest and following constant load cycling which may contribute to reduced exercise tolerance with carbonic anhydrase inhibition.

Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia

Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilatory failure and hypercapnia. On the other hand, it is known that acute metabolic acidosis can also negatively affect (respiratory) muscle function and, therefore, could lead to a deterioration of respiratory failure. Moreover, we reasoned that the impact of metabolic acidosis on respiratory muscle strength and respiratory muscle endurance could be more pronounced in COPD patients as compared to asthma patients and healthy subjects, due to already impaired respiratory muscle function. In this study, the effect of metabolic acidosis was studied on peripheral muscle strength, peripheral muscle endurance, airway resistance, and on arterial carbon dioxide tension (PaCO(2)). Acute metabolic acidosis was induced by administration of ammonium chloride (NH(4)Cl). The effect of metabolic acidosis was studied on inspiratory and expiratory muscle strength and on respiratory muscle endurance. Effects were studied in a randomized, placebo-controlled cross-over design in 15 healthy subjects (4 male; age 33.2 +/- 11.5 years; FEV(1) 108.3 +/- 16.2% predicted), 14 asthma patients (5 male; age 48.1 +/- 16.1 years; FEV(1) 101.6 +/- 15.3% predicted), and 15 moderate to severe COPD patients (9 male; age 62.8 +/- 6.8 years; FEV(1) 50.0 +/- 11.8% predicted). An acute metabolic acidemia of BE -3.1 mmol x L(-1) was induced. Acute metabolic acidemia did not significantly affect strength or endurance of respiratory and peripheral muscles, respectively. In all subjects airway resistance was significantly decreased after induction of metabolic acidemia (mean difference -0.1 kPa x sec x L(-1) [95%-CI: -0.1 - -0.02]. In COPD patients PaCO(2) was significantly lowered during metabolic acidemia (mean difference -1.73 mmHg [-3.0 - -0.08]. In healthy subjects and in asthma patients no such effect was found. Acute metabolic acidemia did not significantly decrease respiratory or peripheral muscle strength, respectively muscle endurance in nomal subjects, asthma, or COPD patients. Metabolic acidemia significantly decreased airway resistance in asthma and COPD patients, as well as in healthy subjects. Moreover, acute metabolic acidemia slightly improved blood gas values in COPD patients. The results suggest that stimulation of ventilation in respiratory failure, by induction of metabolic acidemia will not lead to deterioration of the respiratory failure.

Symposium 6: Young people, artificial nutrition and transitional care The nutritional challenges of the young adult with cystic fibrosis: transition

Cystic fibrosis (CF) is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. Intestinal malabsorption occurs in approximately 90% of patients. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. For many young adults requirements will be 120-150% of the age-related estimated average requirement. To meet these energy needs patients are encouraged to eat a high-fat high-energy diet with appropriate pancreatic enzyme supplements. Many patients are unable to achieve an adequate intake as a result of a variety of factors including chronic poor appetite, infection-related anorexia, gastro-oesophageal reflux and abdominal pain. Oral energy supplements and enteral tube feeding are widely used. Nutritional support has been shown to improve nutritional status and stabilise or slow the rate of decline in lung function. With such emphasis on nutritional intake and nutritional status throughout life, poor adherence to therapies and issues relating to body image are emerging. The median survival of patients with CF is increasing. CF is now considered a life-limiting disease of adulthood rather than a terminal childhood illness. With increased longevity new challenges are emerging that include the transition of young adults with CF to adult services, CF-related diabetes, disordered eating, osteoporosis, liver disease and transplantation.

Recent advances and current clinical perspectives in the diagnosis and treatment of glycogenosis type II

Glycogenosis type II (GSDII), or acid maltase deficiency, is a disorder affecting skeletal and cardiac muscle and is caused by a deficiency of acid alpha-glucosidase (GAA). The disease encompasses a wide spectrum of clinical presentations, ranging from very severe cases presenting soon after birth (the “classic” infantile form) to milder, late-onset cases. Infant patients show a rapidly progressive course of the disease, with muscle weakness, hypertrophic cardiomyopathy, and death usually before the first year of age; alpha-glucosidase is virtually absent. Affected children and adults show a more slowly progressing myopathy with decreased limb strength and often impaired respiratory muscle function. The adult-onset form was first recognized by Engel.1 Variable levels of GAA were described in muscle and leukocytes from patients with infantile, childhood, and adult forms by Engel and Angelini,2 whereas morphologic and biochemical abnormalities were also found in adult-cultured fibroblasts,3 showing the multisystemic involvement of the enzyme defect. In this educational supplement, two articles describe this prototypic lysosomal disorder. The first article deals with the diagnosis of GSDII, and the second, by the same group of authors, is about suggested management to achieve the best medical practice. Although a rare disease, adult-onset GSDII can be challenging for many neurologists, because advances in the diagnosis and long-term treatment are relevant issues. The exact diagnosis of late-onset GSDII is still a controversial problem, because histopathologic, biochemical, and molecular studies of such patients are needed. Late-onset GSDII diagnosis may be difficult and missed on a routine muscle biopsy as pathology could be normal in certain muscles or be mild or not noted.4 Therefore, the combined use of muscle histopathology, …

Impairment of respiratory muscle function in pulmonary hypertension

It has been suggested that impaired respiratory muscle function occurs in patients with PH (pulmonary hypertension); however, comprehensive investigations of respiratory muscle function, including the application of non-volitional tests, needed to verify impairment of respiratory muscle strength in patients with PH have not yet been performed. In the present study, respiratory muscle function was assessed in 31 patients with PH (20 females and 11 males; mean pulmonary artery pressure, 51+/-20 mmHg; median World Health Organization class 3.0+/-0.5; 25 patients with pulmonary arterial hypertension and six patients with chronic thromboembolic PH) and in 31 control subjects (20 females and 11 males) well-matched for gender, age and BMI (body mass index). A 6-min walking test was performed to determine exercise capacity. Volitionally assessed maximal inspiratory (7.5+/-2.1 compared with 6.2+/-2.8 kPa; P=0.04) and expiratory (13.3+/-4.2 compared with 9.9+/-3.4 kPa; P<0.001) mouth pressures, sniff nasal (8.3+/-1.9 compared with 6.6+/-2.2 kPa; P=0.002) and transdiaphragmatic (11.3+/-2.5 compared with 8.7+/-2.5 kPa; P<0.001) pressures, non-volitionally assessed twitch mouth (1.46+/-0.43 compared with 0.97+/-0.41 kPa; P<0.001) and transdiaphragmatic (2.08+/-0.55 compared with 1.47+/-0.72 kPa; P=0.001) pressures during bilateral anterior magnetic phrenic nerve stimulation were markedly lower in patients with PH compared with control subjects. Maximal inspiratory mouth (r=0.58, P<0.001) and sniff transdiaphragmatic (r=0.43, P=0.02) pressures were correlated with the 6-min walking distance in patients with PH. In conclusion, the present study provides strong evidence that respiratory muscle strength is reduced in patients with PH compared with well-matched control subjects. Furthermore, the 6-min walking distance is significantly linked to parameters assessing inspiratory muscle strength.