Patients with chronic obstructive pulmonary disease (COPD) complain of dyspnea and fatigue. We sought to estimate the prevalence of high fatigue in this population and to determine whether individuals with high fatigue had a different response to pulmonary rehabilitation.

This observational study was embedded within a randomized trial. Participants underwent 3 months of pulmonary rehabilitation including education and exercise training. We divided 251 individuals into low and high fatigue groups using population normal scores of the SF-36 vitality domain. Baseline data included spirometry, 6-minute walk distance (6MWD), peak exercise capacity, constant workrate cycling endurance time, and questionnaires including the St. George's and Chronic Respiratory questionnaires (SGRQ, CRQ). The response to pulmonary rehabilitation was evaluated using changes in these measures at 3 months and 1 year after entry.

High fatigue was present in 97/251 (39%) of patients. High fatigue patients were younger, had more depressive symptoms, greater dyspnea and poorer SGRQ scores (p < 0.01). They also had lower 6MWD, endurance times, and peak volume of oxygen consumption (VO(2); p < 0.05). Patients in both groups improved similarly in their dyspnea, the 6MWD and endurance time. High-fatigue patients had greater improvements in both the CRQ fatigue (by 0.74 more points) and the SGRQ scores (by 6.0 points; p < 0.01), with clinically significant gains maintained at 1 year.

This study suggests that high levels of fatigue is a common feature in patients with COPD. They have a lower exercise capacity and a lower health status. However, they benefit from pulmonary rehabilitation.

Both chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer amongst smokers.

Cigarette smoke induces the release of many inflammatory mediators and growth factors including TGF-β, EGFR, IL-1, IL-8 and G-CSF through oxidative stress pathways and this inflammation may persist for decades after smoking cessation. Mucus production is also increased by these inflammatory mediators, further linking airway inflammation to an important mechanism of lung cancer. A greater understanding of the molecular and cellular pathobiology that distinguishes smokers with lung cancer from smokers with and without COPD is needed to unravel the complex molecular interactions between COPD and lung cancer.

By understanding the common signalling pathways involved in COPD and lung cancer the hope is that treatments will be developed that not only treat the underlying disease process in COPD, but also reduce the currently high risk of developing lung cancer in these patients.

Asthma in the adult patient is a complex clinical syndrome. Multiple patient phenotypes and subphenotypes exist that contribute to disease heterogeneity. Whether adult asthma begins in utero, develops in childhood, or manifests for the first time in adulthood is not completely understood, nor are the mechanisms fully delineated. I

n this chapter, we update definitions that apply to this group, emphasize epidemiologic factors and pathogenic mechanisms, diagnosis, therapeutic options, and controversies regarding drug safety. Finally, we provide a brief discussion of biomarker technologies and novel therapies with the potential to impact adult-onset asthma outcomes.

Atopic asthma results from airway inflammation triggered by an environmental allergen. Symptoms include wheezing, dyspnea and cough, airway narrowing and/or hyperresponsiveness to several inhaled stimuli. Inflammation develops in a two-phase fashion.

The first phase after exposure to the allergen consists of degranulation and release of both histamine and other stored preformed inflammatory mediators as well as newly synthesized ones, including cytokines, all of which increase mucus secretion and smooth muscle contraction.

The second phase occurs later and lasts longer; it is due to different molecules: several cytokines and chemokines, arachidonic acid derivatives, enzymes such as metalloproteinases and cell adhesion molecules. Cytokines are key players in the chronic inflammation in asthma patients, but details on their role and interactions still remain undetermined. Recent evidence suggests that allergic asthma is a multifaceted condition actively controlled by effector as well as regulatory T cells (Tregs). T helper (Th) 2 cells and Th17 cells increase airway inflammation, while Tregs are anti- inflammatory. Cytokines are involved in the development and activation of all T cell subpopulations. They are also involved directly or indirectly in most approaches to asthma treatment. Several cytokines have been tested as therapeutic targets and some of the currently used therapies like corticosteroids, beta agonists and allergen immunotherapy affect cytokine production.

The increased knowledge on cytokine interplay and lymphocyte subsets should generate new therapeutic strategies in the near future.