Respiratory muscle training with enzyme replacement therapy improves muscle strength in late - onset Pompe disease.

Background Pompe disease is an autosomal recessive metabolic disorder caused by the deficiency of the lysosomal enzyme acid \u3b1-glucosidase. This deficiency leads to glycogen accumulation in the lysosomes of muscle tissue causing progressive muscular weakness particularly of the respiratory system. Enzyme replacement therapy (ERT) has demonstrated efficacy in slowing down disease progression in infants. Despite the large number of studies describing the effects of physical training in juvenile and adult late onset Pompe disease (LOPD). There are very few reports that analyze the benefits of respiratory muscle rehabilitation or training. Methods The effectiveness of respiratory muscle training was investigated using a specific appliance with adjustable resistance (Threshold). The primary endpoint was effect on respiratory muscular strength by measurements of MIP and MEP. Eight late-onset Pompe patients (aged 13 to 58 years; 4 female, 4 male) with respiratory muscle deficiency on functional respiratory tests were studied. All patients received ERT at the dosage of 20 mg/kg/every 2 weeks and underwent training with Threshold at specified pressures for 24 months. Results A significant increase in MIP was observed during the follow-up of 24 month: 39.6 cm H2O (+ 25.0%) at month 3; 39.5 cm H2O (+ 24.9%) at month 6; 39.1 cm H2O (+ 23.7%) at month 9; 37.3 cm H2O (+ 18.2%) at month 12; and 37.3 cm H2O (+ 17.8%) at month 24. Median MEP values also showed a significant increase during the first 9 months: 29.8 cm H2O, (+ 14.3%) at month 3; 31.0 cm H2O (+ 18.6) at month 6; and 29.5 cm H2O (+ 12.9) at month 9. MEP was then shown to be decreased at months 12 and 24; median MEP was 27.2 cm H2O (+ 4.3%) at 12 months and 26.6 cm H2O (+ 1.9%) at 24 months. The FVC remain stable throughout the study. Conclusion An increase in respiratory muscular strength was demonstrated with Threshold training when used in combination with ERT

ERS International Congress 2023: highlights from the Pulmonary Vascular Diseases Assembly.

peer reviewedPulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation

Chronic inflammation and frequent exacerbations in patients with COPD: the role of PDE4 inhibitors

Inflammation represents an important hallmark of several diseases. In COPD the inflammatory lung response may be chronic and dysregulated with accumulation of inflammatory cells that causes lung parenchyma damage and airway remodeling. The inflammatory cascade involves different cells, mediators, proteins, oxygen species that leads the local inflammation to become systemic and promotes comorbidities and complications. Different stimuli may worsen the COPD pathology, including the well known COPD exacerbation, a peak of local and systemic inflammation. Also hypoxia may stimulate inflammatory genes worsening local and systemic level of inflammation. Understanding the inflammation can allow us to differentiate COPD phenotype and lead as to personalize the therapy. Several have the specific target of inflammation, particularly PDE4 inhibitors may have a role in certain COPD phenotype

Venous thromboembolism in sarcoidosis: Mere comorbidity or catalyst for disease evolution?

International audienc

Balloon pulmonary angioplasty: are we there yet? Lessons learned and unanswered questions

International audienc

Exercise training for patients with pulmonary arterial hypertension

In spite of evidence-based consensus recommendations on exercise training for patients with pulmonary arterial hypertension (PAH) its use outside specialized rehabilitation Centers has been accounted a handful of reports. Dyspnoea and fatigue are common symptoms reducing the exercise tolerance of subjects with PAH even when specific drug are correctly administered. Moreover, the mechanisms of exercise limitation in subjects with PAH are known and thandful of reports. There is evidence of impaired signaling between the periphery and central hemodynamic performance. Exercise training has recently been proven to be effective and safe to enhance physical performance in patients with PAH already treated with specific drug therapy. The rationale of training in PAH has been specifically proven also in experimental animal models of PAH. Moreover, repeated positive results in randomized controlled trials and observational studies in humans gave convincing evidence on the beneficial effects of exercise training as a routine treatment for patients with PAH. To date only 3 small randomized controlled trials and several non-randomized experiences were published in the last decade. Nevertheless, there is a full concordance among all studies, unrespective of the design, training protocol and any possible bias. Exercise training showed to improve physical performance and daily activity, reducing dyspnoea and fatigue, and enhancing the quality of life and muscle strength. So, the final message from the available literature reports is a strong recommendation to adopt exercise training and cardiopulmonary rehabilitation programs for any patient suffering from exertional dyspnoea and fatigue. Many questions remain unanswered regarding the optimization of the exercise training and rehabilitation programs. Ongoing rehabilitative trials in patients with PAH will help answer some of the remaining questions

Epidemiology of Tuberculosis and the Rise of XDR-TB

The global spread of multidrug-resistant strains of tuberculosis (TB) mycobacteria was one of the main reasons leading the World Health Organisation to launch the Stop TB program worldwide. In spite of a slow decline of TB incidence and mortality worldwide, multidrug-resistant TB (MDR-TB) has increased in several countries. MDR-TB is caused by organisms that are resistant to at least isoniazid and rifampicin. The most drug-resistant forms of TB are the extensively drug-resistant TB (XDR-TB) strains caused by organisms that are resistant also to fluoroquinolones and any of the second-line anti-TB injectable drugs. XDR-TB can take 2 years or more to treat with drugs that are less effective, more toxic, and more expensive. Mortality for XDR-TB is very high, and the risk of the transmission between persons of XDR-TB strains is a matter of concern for health systems. Major issues associated with enhanced XDR-TB are non-implementation of DOT (directly observed therapy) and DOT expansion strategies, the insufficient supply or the poor quality of the anti-tuberculosis drugs, and the inadequate intake of the anti-tuberculosis medicines. Nevertheless, prior treatment of MDR-TB with second-line drugs is the strongest associated factor increasing the risk for XDR tuberculosis more than fourfold. Specialized rapid, effective diagnostic methods, including drug-sensitivity testing, are essential for a precise diagnosis of XDR-TB, and subsequent proper treatment. The global rise and spread of XDR-TB have serious effects on TB-control programs, and urge effective health policy responses. National TB control programmes working with all health services can prevent XDR-TB by ensuring that all the physicians and professionals caring for people with TB adhere to the International Standards for TB Care. Specialized centres at regional and national levels should be dedicated to care for difficult-to-treat and untreatable patients with XDR-TB

Respiratory muscle training with enzyme replacement therapy improves muscle strength in late - onset Pompe disease

Background: Pompe disease is an autosomal recessive metabolic disorder caused by the deficiency of the lysosomal enzyme acid α-glucosidase. This deficiency leads to glycogen accumulation in the lysosomes of muscle tissue causing progressive muscular weakness particularly of the respiratory system. Enzyme replacement therapy (ERT) has demonstrated efficacy in slowing down disease progression in infants. Despite the large number of studies describing the effects of physical training in juvenile and adult late onset Pompe disease (LOPD). There are very few reports that analyze the benefits of respiratory muscle rehabilitation or training. Methods: The effectiveness of respiratory muscle training was investigated using a specific appliance with adjustable resistance (Threshold). The primary endpoint was effect on respiratory muscular strength by measurements of MIP and MEP. Eight late-onset Pompe patients (aged 13 to 58 years; 4 female, 4 male) with respiratory muscle deficiency on functional respiratory tests were studied. All patients received ERT at the dosage of 20 mg/kg/every 2 weeks and underwent training with Threshold at specified pressures for 24 months. Results: A significant increase in MIP was observed during the follow-up of 24 month: 39.6 cm H2O (+25.0%) at month 3; 39.5 cm H2O (+24.9%) at month 6; 39.1 cm H2O (+23.7%) at month 9; 37.3 cm H2O (+18.2%) at month 12; and 37.3 cm H2O (+17.8%) at month 24. Median MEP values also showed a significant increase during the first 9 months: 29.8 cm H2O, (+14.3%) at month 3; 31.0 cm H2O (+18.6) at month 6; and 29.5 cm H2O (+12.9) at month 9. MEP was then shown to be decreased at months 12 and 24; median MEP was 27.2 cm H2O (+4.3%) at 12 months and 26.6 cm H2O (+1.9%) at 24 months. The FVC remain stable throughout the study. Conclusion: An increase in respiratory muscular strength was demonstrated with Threshold training when used in combination with ERT