New research from Japan brings hope of a new treatment for asthma patients resistant to corticosteroids. In a study researchers from the RIKEN Center for Integrative Medical Sciences and Keio University in Japan report that a type of lymphocytes called natural helper (NH) cells plays a critical role in corticosteroid resistance and demonstrate that the anti-psychotic drug Pimozide can be used to overcome resistance to steroids in severe asthma patients.
Asthma is a chronic disease characterised by a persistent inflammation of the airways. The condition can be controlled with a moderate dose of inhaled corticosteroids in most patients. However, 5-10% of patients with ‘severe asthma’ respond poorly to a maximal dose of steroids. These patients experience uncontrolled and frequent asthma symptoms that have a profound impact on their quality of life and health care costs. Unveiling the mechanism leading to steroid resistance in these patients is therefore crucial for the development of a new, effective therapy.

T lymphocytes and NH cells in the asthmatic lung produce proteins named interleukin (IL)-5 and IL-13 that are responsible for severe airway inflammation. In asthma patients, inhaled steroids function by suppressing both T lymphocytes and NH cells.
However, in severe asthma patients, another protein called interleukin-33 (IL-33) produced in the airways strongly activates NH cells to produce IL-5 and IL-13, leading to severe airway inflammation.

In the current study, the researchers led by Drs Shigeo Koyasu from RIKEN and Koichiro Asano from Keio University, employed an experimental mouse model for airway inflammation to study the pathway leading to IL-33-mediated NH activation. Their research shows that NH resistance to steroids is induced by the protein thymic stromal lymphopoietin (TSLP), present in the airways of severe asthma patients.

The team tested reagents that block the intracellular signals triggered by TSLP in NH cells. They identified one drug, Pimozide, an approved anti-psychotic drug, that restored the effects of steroids on NH cells.
‘Therefore, administration of Pimozide or related drugs would be an effective treatment in human severe asthmatic patients,’ conclude the authors. RIKEN

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Experts from the Too Fit to Fracture Initiative presented the results of an international consensus process to establish exercise recommendations for people with osteoporosis, with or without spine fractures. The results were presented at the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases in Seville, Spain.

Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method, the international multidisciplinary panel examined literature on exercise effects on: 1) falls, fractures, BMD, and adverse events for individuals with osteoporosis or spine fractures; and 2) pain, quality of life, and physical function after spine fracture. Evidence was rated as high, moderate, low, or very low.

In addition, a consensus process was used to established recommendations on assessment, exercise, and physical activity in the context of three cases with varying risk – one having osteoporosis based on bone density; one having osteoporosis and 1 spine fracture; and one having osteoporosis and multiple spine fractures, hyperkyphosis and pain.

The panel recommends that all individuals with osteoporosis should engage in a multicomponent exercise programme that includes resistance and balance training; they should not engage in aerobic training to the exclusion of resistance or balance training.

Other key points included:
current national physical activity guidelines are appropriate for individuals with osteoporosis in the absence of spine fracture, but not for those with spine fracture;
after spine fracture, aerobic activity of moderate intensity is preferred to vigorous; physical therapy consultation is recommended;
daily balance training and endurance training for spinal extensor muscles are recommended for all individuals with osteoporosis;
restrictions are a disincentive to activity participation, and for people with osteoporosis but no history of spine fracture, desired activities should be encouraged if they can be performed safely or modified;
health care providers should provide guidance on safe movement, rather than providing generic restrictions (e.g., lifting);
physical or occupational therapist consult is recommended for advice on exercise and physical activity among those with a history of spine fracture, particularly in the presence of balance or posture impairments, pain, comorbid conditions or that increase the risk of adverse events with exercise or activity, or unsafe movement patterns.

Lead author Dr Lora Giangregorio, University of Waterloo, Waterloo, Canada, stated, ‘People with osteoporosis and spinal fractures should be encouraged to participate in resistance training and balance training, as the strongest evidence we have supports multimodal exercise programs. We have developed evidence-based recommendations, as well as a report that addresses the ‘frequently asked questions’ of patients and health care providers around physical activity. We hope that the recommendations are helpful to health professionals worldwide as they guide their osteoporosis patients in safe, effective – and enjoyable – exercise regimens.’ International Osteoporosis Foundation