Asthma & ExercisePhysiology and

Pathophysiology

Michele R. Shaw, RN, PhD

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)

T Lymphocytes

Produce large amounts of cytokinesCD4+ (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)

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).

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

Airway RemodelingBasement Membrane Thickening

(Barbato’s et al)

Airway RemodelingIncreased Eosinophils

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)

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.

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

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.

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.

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)

Asthma & ExercisePhysiology and

Pathophysiology

Michele R. Shaw, RN, PhD