Age-related changes in immune function: Effect on airway inflammation

Abstract

Immunosenescence is defined as changes in the innate and adaptive immune response associated with increased age. The clinical consequences of immunosenescence include increased susceptibility to infection, malignancy, and autoimmunity, decreased response to vaccination and impaired wound healing. However, there are several immune alterations which may facilitate persistence of asthma into late adulthood, or development of asthma after the age of 50-60 years. Asthma in older patients is not uncommon and is a growing population as the average lifespan increases. Specific innate changes which may affect severity of asthma in older patients, or be involved in the development of late onset asthma include impaired in mucociliary clearance, and changes in airway neutrophil, eosinophil and mast cell numbers and function. Additionally, age-related altered antigen presentation and decreased in specific antibody responses may increases the risk of respiratory infections. Respiratory infections exacerbate asthma in older patients, and possibly play a role in the pathogenesis of late onset asthma. Furthermore, cytokine profiles may be modified with aging; some investigators suggesting a trend towards Th2 cytokine expression. This review examines specific innate and adaptive immune responses affected by aging that may impact the inflammatory response in older adults with asthma.

Molecular composition of the alveolar lining fluid in the aging lung

“…The relative changes in complement components observed in the ALF of old mice (decreased C2, increased C3 and C4) indicate that increasing age may lead to problems associated with MAC formation or antibody complex clearance associated with the classical arm of the complement cascade. This is supported by the reported reduced function of antibodies in elderly donors and may contribute to their increased susceptibility to infections (Busse and Mathur 2010;Doria et al 1978;Eaton et al 2004). Similarly, our data indicate that the low levels of C2 and high levels of factor B observed in the ALF of old mice may favor the alternative pathway in lower respiratory tract secretions (Robertson et al 1976).…”

Effects of omalizumab in severe asthmatics across ages: A real life Italian experience

“…All these features, different in younger subjects, may explain the reduced effect of Omalizumab in the elderly. Actually, the development of late-onset adult asthma may be also the clinical consequence of immunosenescence that would lead to decline in functionality of the immune system with increasing age (35)(36)(37)(38). This age-related process determines a progressive impaired mucociliary clearance, changes in airway neutrophil, eosinophil, and mast cell numbers and function over an altered antigen presentation and decreased specific antibody responses (37).…”

“…Furthermore, this immunosenescence and its associated chronic low grade systemic "inflammaging" may contribute to the development and progression of pulmonary disease in older individuals (34,37). Therefore, immunosenescence may favor a neutrophilic inflammation that determines a more severe disease and less effective asthma treatments in the elderly (38).…”

Impact of Age and Sex on Response to Asthma Therapy

“…More recent data suggest that older patients have increased "small airway" involvement, increased neutrophilic inflammation, and decreased eosinophil function and specific antibody response compared with younger cohorts (9)(10)(11). These important, but understudied age-related changes in pulmonary function, bronchial hyperresponsiveness, host defense, and inflammation highlight the need for more investigation into this important group of patients.…”