Exertional dyspnea in symptomatic patients with mild COPD is associated with the combined deleterious effects of higher ventilatory demand and abnormal dynamic ventilatory mechanics, both of which are potentially amenable to treatment.

prevalence of activity-related breathlessness increases with age, particularly in women, but the specific underlying mechanisms have not been studied. This novel cross-sectional study was undertaken to examine the effects of age and sex, and their interaction, on the perceptual and ventilatory responses to incremental treadmill exercise in 73 healthy participants (age range 40 -80 yr old) with normal pulmonary function. Age-related changes at a standardized oxygen uptake (V O2) during exercise included significant increases in breathlessness ratings (Borg scale), ventilation (V E), ventilatory equivalent for carbon dioxide, and the ratio of tidal volume (VT) to dynamic inspiratory capacity (IC) (all P Ͻ 0.05). These changes were quantitatively similar in women (n ϭ 39) and in men (n ϭ 34). For the group as a whole, exertional breathlessness ratings increased as resting static inspiratory muscle strength diminished (P ϭ 0.05), as exercise ventilation increased relative to capacity (P ϭ 0.013) and as the VT/IC ratio increased (P ϭ 0.003) during exercise. Older women (60 -80 yr old, n ϭ 23) reported greater (P Ͻ 0.05) intensity of exertional breathlessness at a standardized V O2 and V E than age-matched men (n ϭ 16), despite similar age-related changes in ventilatory demand and dynamic ventilatory mechanics. These increases in breathlessness ratings in older women disappeared when sex differences in baseline maximal ventilatory capacity were accounted for. In conclusion, although increased exertional breathlessness with advancing age is multifactorial, contributory factors included higher ventilatory requirements during exercise, progressive inspiratory muscle weakness, and restrictive mechanical constraints on VT expansion related to reduced IC. The sensory consequences of this age-related respiratory impairment were more pronounced in women, who, by nature, have relatively reduced maximal ventilatory reserve. dyspnea; aging; inspiratory capacity CARDIOVASCULAR FACTORS are widely accepted as a proximate limit to maximal oxygen uptake (V O 2 ) during weight-bearing exercise in healthy humans (42,48). By contrast, the respiratory system is regarded as relatively "overbuilt" and less likely to contribute to exercise limitation except in elite athletes at very high power outputs (15, 21). However, it is recognized that in sedentary older individuals, intolerable exertional breathlessness may contribute to exercise limitation even before physiological maxima are attained (39). A number of studies have reported that more than 30% of the elderly (Ͼ65 yr) experience breathlessness during activities of daily living (23,24,30,47). The nature and mechanisms of exertional breathlessness in older healthy humans are poorly understood.While the physiological effects of aging on the respiratory system are well established (14,25,40), the interaction between these changes in respiratory system compliance, muscle function, and ventilation/perfusion (V /Q ) matching and the perceptual responses to physical exertion is largely unknow...

The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre-and post-bronchodilator (salbutamol). COPD was likely the predominant diagnosis but patients with asthma may have been included. We studied 2,265 subjects (61% male), age 65 ± 9 years (mean ± SD) with a postbronchodilator FEV 1 /FVC <0.70. We examined relationships between indices of airway obstruction and lung hyperinflation, and measured responses to bronchodilation across subgroups stratified by GOLD criteria. In GOLD stage I, vital capacity (VC) and inspiratory capacity (IC) were in the normal range; pre-bronchodilator residual volume (RV), functional residual capacity (FRC) and specific airway resistance were increased to 135%, 119% and 250% of predicted, respectively. For the group as a whole, RV and FRC increased exponentially as FEV 1 decreased, while VC and IC decreased linearly. Regardless of baseline FEV 1 , the most consistent improvement following bronchodilation was RV reduction, in terms of magnitude and responder rate. In conclusion, increases (above normal) in airway resistance and plethysmographic lung volumes were found in those with only minor airway obstruction. Indices of lung hyperinflation increased exponentially as airway obstruction worsened. Those with the greatest resting lung hyperinflation showed the largest bronchodilator-induced volume deflation effects. Reduced air trapping was the predominant response to acute bronchodilation across severity subgroups.

Summary. von Willebrand Factor (VWF) is a large multimeric glycoprotein involved in the transport and protection of factor VIII and in mediating platelet±subendothelium and platelet±platelet interactions. We have documented the presence of a single nucleotide polymorphism (SNP) at nucleotide (nt) 21793 (G 0´36 or C 0´64) in the VWF 5 Hflanking sequence. This polymorphism is in strong linkage disequilibrium with the previously reported SNPs at nts 21234, 21185 and 21051 and, like this other group of polymorphisms, shows a significant association with plasma VWF levels. This association is more marked in subjects who are more than 40 years of age. Further, circumstantial evidence to support a role for the 21793 sequence in regulating VWF expression comes from our demonstration of differential binding of endothelial cell nuclear proteins, including the transcription factor NFkB, by this sequence. In summary, the association of the 21793 SNP with plasma VWF levels provides additional evidence for the role of the VWF regulatory region between nts 21793 and 21051 in controlling VWF expression.

No abstract