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Asthma & Exercise Physiology and Pathophysiology

Asthma & Exercise Physiology and Pathophysiology

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Asthma & Exercise Physiology and Pathophysiology

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  1. Asthma & ExercisePhysiology and Pathophysiology Michele R. Shaw, RN, PhD

  2. Asthma General Mechanisms • Inflammatory response • Involving T cells, mast cells, basophils, macrophages, T helper cells, and eosinophils (Hamid et al., 2003; Macfarlane et al., 2000; Wegmann et al., 2005) • T lymphocytes (predominant cells involved in asthmatic airway mucosa) (Hamid et al., 2003)

  3. T Lymphocytes • Produce large amounts of cytokines • CD4+ (T helper cells) • Assist in the inflammatory response by signaling other cells to the area of inflammation. • CD8+ (T cytotoxic cells) • Assist by actually attempting to kill the invader (Hamid et al., 2003)

  4. CD4+ T Helper Cells • Broken down into Th1, Th2, and Th3 • TH3 cells are another subtype of CD4+ cells and are suggested to be regulatory T helper cells. • Th3 are involved in high level production of transforming growth factor ß (TGF) • TGF, by binding to it’s type 1 and type 2 receptor sites, is thought to exert many physiological effects including, both anti-inflammatory and profibrotic activities. • Role of TGF is debated as it can assist in the ANTI-inflammatory process and/or have a profibrotic effect. (Barbato et al., 2003).

  5. Cellular Counts in Subepithelium(Barbato et al., 2003) Children with Asthma Children with Atopy Control Children Eosinophils 48 (13–376)* 81 (8–330)* 15 (0–72) Neutrophils 87 (16–244) 98 (19–225) 90(38–268) Mast cells 23 (0–132) 93 (0–213) 56 (0–157) CD4 T-lymph’s 89 (42–535) 259 (97–357) 213 (11–316) Macrophages 175 (56–344) 138 (68–225) 137 (11–244) TGFß1+ cells 182 (66–354) 172 (78–372) 87 (9–470) TGFß-RI+ cells 623 (291–1167) 550 (308–1381) 952 (196–1,092) TGFß-RII+ cells 179 (47–332)* 543 (391–676) 479 (71–948) *Values are expressed as cells/mm2 *p<0.05 as compared with control children

  6. Airway RemodelingBasement Membrane Thickening(Barbato’s et al)

  7. Airway RemodelingIncreased Eosinophils

  8. Asthma and Exercise Phys/Pathophysiology • Two Hypotheses: • Heat loss & the re-warming of the airways leading to vascular engorgement = bronchoconstriction (McFadden & Gilbert, 1994; Anderson & Daviskas, 2000). • Dehydration of airways = changes initiating epithelial and mast cell activation = inflammatory process (McFadden & Gilbert; Anderson & Daviskas)

  9. Exercise as a non-drug treatment? • Pastva et al. (2004) hypothesized that moderate aerobic exercise would attenuate the inflammatory activities usually seen within the asthmatic airway. • Utilized a mouse model of atopic asthma. • Compared sedentary mice to an exercised group.

  10. Sedentary Vs. Exercised Airway in a Mouse Model of Atopic Asthma (Pastva et al., (2004)

  11. Aerobic Exercise as Treatment… • Pastva et al (2004) findings demonstrate decreased inflammatory processes, including: • Mucus production & epithelial cell hypertrophy (lung tissue) • Cellular infiltrate & total protein concentration (airway lumen) • Secretion of the proinflammatory mediators (KC (a chemokine), IL-4, & IL-5 into the airway lumen) • Expression of the adhesion molecule VCAM-1 (vascular cell adhesion molecule-1 = promotes the adhesion of lymphocytes, monocytes, eosinophils, and basophils) (intact lung tissue) • Production of OVA-specific IgE in serum. • Summary: Data suggest moderate aerobic exercise reduces airway inflammation. Moderate training may provide beneficial anti-inflammatory effects in asthmatic humans.

  12. Asthma Summary • Complex disease with multiple etiologies. • Environmental & Genetic components • Decreased physical activity among school aged children may be a risk factor for development of asthma. • In addition, decreased activity may lead to an increase in symptom severity. • Need for further research among school aged asthmatic children, particularly in the area of exercise as a non-drug treatment.

  13. Asthma and Exercise Model: Moderate Aerobic Exercise (Moderate aerobic exercise = 60 minutes, 3 times per week) ↓ ↓ Inflammatory Response ↓ ↓ ↓Asthma Symptoms & Severity↓ (among school aged children)

  14. Asthma & ExercisePhysiology and Pathophysiology Michele R. Shaw, RN, PhD