Considerations for managing chronic obstructive pulmonary disease in the elderly

George E Taffet,1 James F Donohue,2 Pablo R Altman31Geriatrics Section, Geriatrics and Cardiovascular Sciences, Baylor College of Medicine, The Methodist Hospital, Houston, TX, 2Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, 3Medical Affairs, Mylan Specialty L.P., Basking Ridge, NJ, USAAbstract: Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years. Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers. However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways. In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly. Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis. Nebulizers should be considered for patients unable to use handheld inhalers properly. What follows is a review of issues associated with COPD and its treatment in the elderly patient.Keywords: chronic obstructive pulmonary disease, inhaler, device, cognition, disability, comorbidities, maintenance therap

Conventional protein kinase C and atypical protein kinase Cζ differentially regulate macrophage production of tumour necrosis factor-α and interleukin-10

In chronic inflammatory diseases such as rheumatoid arthritis, joint macrophages/monocytes are the major source of pro- and anti-inflammatory cytokines. Little is understood regarding the signalling pathways which determine the production of the pro-inflammatory cytokine, tumour necrosis factor-α (TNF-α) and the anti-inflammatory cytokine, interleukin-10 (IL-10). Two pathways integral to macrophage function are the protein kinase C (PKC)- and the cAMP-dependent pathways. In this report, we have investigated the involvement of PKC and cAMP in the production of TNF-α and IL-10 by peripheral blood monocyte-derived macrophages. The utilization of the PKC inhibitors Go6983, Go6976 and RO-32-0432 demonstrated a role for conventional PKCs (α and β) in the production of TNF-α in response to stimulation by lipopolysaccharide and phorbol 12-myristate 13-acetate (PMA)/ionomycin. PKC stimulation resulted in the downstream activation of the p42/44 mitogen-activated protein kinase (MAPK) pathway which differentially regulates TNF-α and IL-10. The addition of cAMP however, suppressed activation of this MAPK and TNF-α production. Cyclic-AMP augmented IL-10 production and cAMP response element binding protein activation upon stimulation by PMA/ionomycin. In addition, cAMP activated PKCζ; inhibition of which, by a dominant negative adenovirus construct, selectively suppressed IL-10 production. These observations suggest that pro-inflammatory and anti-inflammatory cytokines are differentially regulated by PKC isoforms; TNF-α being dependent on conventional PKCs (α and β) whereas IL-10 is regulated by the cAMP-regulated atypical PKCζ