Physiologic Determinants of Exercise Capacity in Pulmonary Langerhans Cell Histiocytosis: A Multidimensional Analysis.

BACKGROUND: Reduced exercise capacity severely impacts quality of life in pulmonary Langerhans cell histiocytosis. Ascertaining mechanisms that impair exercise capacity is necessary to identify targets for symptomatic treatments. METHODS: Dyspnea, pulmonary function tests and cardiopulmonary exercise test were analysed in 62 study participants. Data were compared between subjects with impaired and normal aerobic capacity (V'O2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included V'O2 peak as the dependent variable and principal components as covariates. RESULTS: V'O2 peak was reduced in 44 subjects (71%). Subjects with impaired aerobic capacity presented: (i) decreased FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA and increased AaDO2, (ii) increased ventilatory equivalents at ventilatory threshold, VD/VT peak, AaDO2 peak and PaCO2 peak and decreased ventilatory reserve and PaO2 peak. There was no difference between groups in dyspnea scores. Principal component analysis extracted 4 principal components interpreted as follows: PC1: gas exchange; PC2: "pseudorestriction"; PC3: exercise-induced hyperpnea; PC4: air trapping. Multivariate analysis explained 65% of V'O2 peak. The 4 principal components were independently associated with V'O2 peak (ßcoefficients: PC1: 9.3 [4.6; 14], PC2: 7.5 [3; 11.9], PC3: -5.3 [-9.6;-1.], PC4: -9.8 [-14,9;-4.7]). CONCLUSION: Impaired exercise capacity is frequent in pulmonary Langerhans cell histiocytosis. It is mainly caused by pulmonary changes but is not associated with increased dyspnea intensity. Therefore, treating the lung represents a relevant approach for improving exercise capacity, even in patients experiencing mild dyspnea.

Influence of cisplatin-use, age, performance status and duration of chemotherapy on symptom control in advanced non-small cell lung cancer: detailed symptom analysis of a randomised study comparing cisplatin-vindesine to gemcitabine.

BACKGROUND: We previously reported that treatment of patients with symptomatic advanced non-small cell lung cancer with single agent Gemcitabine (GEM) resulted in a superior clinical-benefit response rate (RR) compared to cisplatin-based combination chemotherapy. We now report the detailed individual symptom control analysis, and the influence of cisplatin-use, age, performance status (PS) and duration of treatment. PATIENTS AND METHODS: Patients received either GEM (1000 mg/m(2), days 1, 8 and 15) or cisplatin (100 mg/m(2), day 1) plus Vindesine (3 mg/m(2), days 1 and 15) (PV), both every 4 weeks. Scores of 9 symptoms were listed weekly by the patient on visual analogue scales. Improvement of a symptom was defined as 2 consecutive cycles of improvement over baseline. RESULTS: Baseline symptoms in the 169 patients were well balanced between the 2 arms (84 GEM, 85 PV). Both patients with objective response and disease stabilisation had clearly better symptom control than those with disease progression. Symptom control in both arms was similar for 'disease-specific' symptoms such as cough, dyspnea, pain or haemoptysis. Compared to PV, a significantly larger number of GEM-patients had better scores for 'constitutional' items such as anorexia (P=0.007), ability to carry on with daily activities (P=0.04) and overall impression of quality-of-life (P=0.008). Symptom control was very similar in younger (<65 years) versus older (>/=65 years) patients, and only slightly better in those with a Karnofsky PS >/=80% compared to those <80%. Most of the symptom improvement occurred in the first 3 cycles, with some further symptom improvement in the following cycles in the GEM-arm only. CONCLUSIONS: Both GEM and PV yield a symptom control rate much higher than expected by the objective tumour RR. GEM is equally effective in controlling 'disease-specific' symptoms, but superior in controlling 'constitutional' symptoms. Most of the symptom control was achieved during the first 3 cycles of treatment, with some further improvement thereafter in the GEM-arm only.

Impaired exercise response in sarcoid patients with normal pulmonary functio.

BACKGROUND AND AIM OF THE WORK: Sarcoidosis is a granulomatous disease with frequent pul monary involvement. Patients generally exhibit a 25-30% reduction in maximal aerobic capacit (VO2max). As most investigations have included patients with both normal and abnormal resting pulmonary function tests (PFT), the mechanisms responsible for this limitation remain unclear. We initiated a prospective study to characterize the cardio-respiratory response to exercise in sarcoid patients with normal resting PFT. METHODS: 19 untreated male patients with biopsy-proven sarcoidosis and 19 age- an sex-matched sedentary healthy controls (38 +/- 8.7 vs 37 +/- 8.7 yrs ; Body Mass Index: 24 +/- 3.05 vs 23 +/- 3.05) were included in the study. All patients had normal resting PFT including diffusing capacity for CO (DLCO) > 80% predicted and normal cardiac status at rest as assessed by EKG and echocardiography. A maximal cycling test was performed in all subjects. RESULTS: True maximal effort was obtaine in all subjects (plasma lactate 9.1 +/- 2.6 vs 11.0 +/- 2.2 mmol l(-1), pH 7.35 +/- 0.04 vs 7.34 +/- 0.04) (patients vs controls). Patients exhibited a 30% lower maximal workload and/or VO2max (2,128 +/- 413 vs 2,909 +/- 387 ml x min(-1)) than controls. Maximal ventilation (79 +/- 21.7 vs 110 +/- 21.7 l x min(-1)) and tital volume (VT) (2,313 +/- 517 ml vs 2,856 +/- 339) were significantly lower in patients than in controls while dead space t tital volume ratio (VD/V(T)) (0.18 +/- 0.09 vs 0.11 +/- 0.04) was higher in patients than in controls. PaO2, PAiO2, and PAi-aO2 at VO2max were not significantly different between patient and controls. Peak exercise EKG was normal in all but one patient. Interestingly, heart rate was significantly lower in patients for all relative exercise intensities > or = 60% VO2max including maximum (159 +/- 21.7 vs 182 +/- 13) CONCLUSION: The present observations indicate a significant maximal exercise limitation in sarcoid patients without significant pulmonary impairment which could be related at least in part to an impaired heart rate response to exercise.