Katherine A. Webb

The role of dynamic hyperinflation (DH) in exercise limitation in chronic obstructive pulmonary disease (COPD) remains to be defined. We examined DH during exercise in 105 patients with COPD (FEV(1) = 37 +/- 13% predicted; mean +/- SD) and studied the relationships between resting lung volumes, DH during exercise, and peak oxygen consumption (VO(2)). Patients completed pulmonary function tests and incremental cycle exercise tests. We measured the change in inspiratory capacity (Delta IC) during exercise to reflect changes in DH. During exercise, 80% of patients showed significant DH above resting values. IC decreased 0.37 +/- 0.39 L or 14 +/- 15% predicted during exercise (p < 0.0005), but with large variation in range. Delta IC correlated best with resting IC, both expressed %predicted (r = -0.50, p < 0.0005). Peak VO(2) (%predicted maximum) correlated best with the peak tidal volume attained (VT standardized as % of predicted vital capacity) (r = 0.68, p < 0.0005), which, in turn, correlated strongly with IC at peak exercise (r = 0.79, p < 0.0005) or at rest (r = 0.75, p < 0.0005). The extent of DH during exercise in COPD correlated best with resting IC. DH curtailed the VT response to exercise. This inability to expand VT in response to increasing metabolic demand contributed importantly to exercise intolerance in COPD.

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44 +/- 13% pred): 96 patients received 18 microg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared. On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105 +/- 40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9 +/- 0.3 Borg scale units. In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.

PURPOSE: We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. PATIENTS AND METHODS: Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. RESULTS: The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. CONCLUSION: This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

Abstract There is considerable intersubject variability in the perceived intensity of breathlessness for a given level of activity among patients with chronic airflow limitation (CAL). To examine possible factors contributing to this variability we compared breathing pattern parameters, dynamic operational lung volumes, and Borg dyspnea ratings in 23 patients with severe CAL and in 10 healthy age-matched normal subjects during cycle ergometry to symptom-limitation. Patients with CAL had significantly (p &amp;lt; 0.01) higher levels of ventilation (% maximal voluntary ventilation) for a given work rate (slope of e(%MVV)/WR(% pred max) = 1.51 ± 0.18 versus 0.63 ± 0.10; mean ± SEM) and greater dynamic lung hyperinflation (DH) (change [Δ] in end-expiratory lung volume [EELVdyn] = +0.31 ± 0.11 L versus −0.16 ± 0.22 L). Compared with normal subjects at a standardized e (30 L/min), the CAL group was more breathless (Borg = 4 ± 1 versus 2 ± 1, p &amp;lt; 0.01) and hyperinflated (EELVdyn = 75 ± 3 versus 46 ± 6 %TLC, p &amp;lt; 0.001; end-inspiratory lung volume [EILVdyn] = 85 ± 3 versus 67 ± 5 %TLC, p &amp;lt; 0.01). Within the CAL group, change in Borg ratings correlated with Δ e(%MVV) (r = 0.77, p &amp;lt; 0.001) and with slope of e(%MVV)/WR(% pred max) (r = 0.48, p &amp;lt; 0.01). Regression analysis selected ΔEILVdyn (or Δ inspiratory reserve volume [ΔIRVdyn]) from various dynamic ventilatory parameters as the strongest predictor of Δ Borg (r = 0.63, p &amp;lt; 0.001). Components of ΔEILVdyn (i.e., ΔEELVdyn, ΔVt) each contributed significantly (p &amp;lt; 0.001) to breathlessness and with A breathing frequency accounted for 61% of the variance in ΔBorg (r = 0.78, f = 38.20, p &amp;lt; 0.001). Accounting for ventilation, EELVdyn continued to contribute significantly to breathlessness; at a standardized e (30 L/min), EELVdyn predicted 31% of the variance in Borg ratings (p &amp;lt; 0.01). Exertional breathlessness in CAL is a function of ventilatory demand and intensifies with encroachment on the inspiratory reserve volume or ventilatory reserve. Acute DH, with its attendant intrinsic mechanical loading, contributes importantly to intersubject variability in the perception of breathlessness for a given ventilation.

Changes in lung hyperinflation, dyspnea, and exercise endurance are important outcomes in assessing therapeutic responses in chronic obstructive pulmonary disease (COPD). Therefore, we studied the reproducibility of Borg dyspnea ratings, inspiratory capacity (IC; to monitor lung hyperinflation), and endurance time during constant-load symptom-limited cycle exercise in 29 patients with COPD (FEV1 = 40 +/- 2% predicted; mean +/- SEM). Responsiveness was also studied by determining the acute effects of nebulized 500 micrograms ipratropium bromide (IB) or saline placebo (P) on these measurements. During each of four visits conducted over an 8-wk period, spirometry and exercise testing were performed before and 1 h after receiving IB or P (randomized, double-blinded). Highly reproducible measurements included: endurance time (intraclass correlation R = 0.77, p < 0.0001); Borg ratings and IC at rest, at a standardized exercise time (STD), and at peak exercise (R > 0.6, p < 0.0001); and slopes of Borg ratings over time, oxygen consumption (V O2), and ventilation (R > 0.6, p < 0.0001). Responsiveness was confirmed by finding a significant drug effect for: change (Delta) in endurance time (p = 0.0001); DeltaBorgSTD and DeltaBorg-time slopes (p < 0.05); and DeltaIC at rest, at STD, and at peak exercise (p = 0.0001). With all completed visits, DeltaBorgSTD correlated better with DeltaICSTD than any other resting or exercise parameter (n = 115, r = -0.35, p < 0.001). We concluded that Borg dyspnea ratings, and measurements of IC and endurance time during submaximal cycle exercise testing are highly reproducible and responsive to change in severe COPD.