High‐Altitude Climate Therapy Reduces Local Airway Inflammation and Modulates Lymphocyte Activation

Abstract

High-altitude climate therapy is a well-established therapeutic option, which improves clinical symptoms in asthma. However, little is known about the underlying immunological mechanisms. The study investigates the influence of high-altitude climate therapy on airway inflammation and cellular components of specific and unspecific immune response. Exhaled NO significantly decreased within 3 weeks of therapy in patients with allergic and intrinsic, moderate and severe asthma. Interleukin-10 (IL-10)-secreting peripheral blood mononuclear cells (PBMC) increased within 3 weeks of therapy in six of 11 patients, whereas transforming growth factor-b 1 -secreting PBMC remained stable. Furthermore, monocyte activation, assessed by CD80 expression significantly decreased during therapy. The frequency of CRTH2-expressing T cells decreased, while regulatory T cells (T reg ) remained stable. FOXP3 and GATA-3 mRNA expression in CD4 þ T cells did not change, while interferon-g and IL-13 mRNA expression decreased in eight of 10 patients. The current data demonstrate that high-altitude climate therapy reduces local airway inflammation. Furthermore, monocytes switch towards a tolerogenic phenotype under high-altitude climate therapy. The T reg /Th2 ratio increases; however, because of the absence of antigens/allergens, no de novo differentiation of Th2 nor T reg cells is observed. The high-altitude climate therapy therefore may form the immunological basis for the endogenous control of allergen-driven diseases.

Associations among high altitude, allergic rhinitis, and bronchial hyperreactivity

“…The CD80 expression level decreased from 5.02% to 3.32% at the end of 3 weeks of HA therapy (p<0.01). [3] Also, and importantly, the Treg/Th2 ratio increased, showing that HA was useful for endogenous control of allergen-triggered disease. [3] After a stay above 3000 m, the plasma levels of the suprarenal hormones norepinephrine, epinephrine, and cortisol elevated.…”

“…[4] Pathogenic hypotheses relevant to HA HA mitigates allergic respiratory disease even when the allergen concentration is high; the mechanism remains poorly understood. The hypoxia-induced reduction in Tlymphocyte numbers may reduce local airway inflammation, [3] or the high levels of suprarenal hormones and/or atrial natriuretic peptide [4,11] may exert protective effects.…”

“…Tregs create peripheral tolerance to allergens and autoantigens by secreting IL-10 and transforming growth factor-β1 (TGF-β1) (these are suppressive cytokines), and by stimulating synthesis of the key FOXP3 transcription factor. [3] One study investigating the effects of HA on airway inflammation and the cell-mediated immune system showed that 3 weeks of HA therapy significantly reduced the exhaled nitric oxide (NO) level, a determinant of local airway inflammation, in patients with intrinsic moderate and severe asthma. Peripheral blood mononuclear cells (PBMCs) secreting IL-10 increased in numbers in 6 of 11 patients, but the numbers of PBMCs secreting TGF-β1 remained unchanged over 3 weeks at HA.…”

“…[1,2] Industrial development, exposure to pollutants, indoor mites and other allergens, and humidity problems are increasing the incidences of allergic airway disease, bronchial responsiveness, and airway inflammation. [3] Several treatment options have been developed. These include nasal steroids and antihistamines and inhaled steroids and β2-agonists.…”

Severe refractory asthma: an update

“…Most patients with severe asthma benefit from a stay at high altitude [102,103]. The high altitude climate offers decreased levels of house dust mite allergens and decreased exposure to pollens, fungal spores and air pollution.…”