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1.  Sustained reduction in bronchial hyperresponsiveness with inhaled fluticasone propionate within three days in mild asthma: time course after onset and cessation of treatment 
Thorax  2003;58(6):500-504.
Background: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks.
Methods: Twenty six asthmatic patients aged 21–59 years were selected for this randomised, double blind, parallel group study. The effect of 250 µg inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV1) by 15% (PD15FEV1) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD15FEV1 were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves.
Results: The increase in PD15FEV1 from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD15FEV1 was 1.85–2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment.
Conclusions: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 µg. The effect tapered within 2 weeks of cessation of treatment.
doi:10.1136/thorax.58.6.500
PMCID: PMC1746689  PMID: 12775860
2.  Hyperventilation syndrome 
Thorax  2001;56(1):84.
doi:10.1136/thorax.56.1.84d
PMCID: PMC1745894  PMID: 11193487
3.  Orthostatic increase of respiratory gas exchange in hyperventilation syndrome 
Thorax  2000;55(4):295-301.
BACKGROUND—Hyperventilation syndrome (HVS) is a common disorder which is difficult to diagnose because of somatic symptoms and its episodic nature. In previous studies respiratory alkalosis in arterial blood was often found during orthostatic tests in patients with HVS. The purpose of this study was to assess these orthostatic changes by non-invasive pulmonary gas exchange measurements and to evaluate whether these responses discriminate patients with HVS from healthy subjects.
METHODS—Respiratory gases were collected with a face mask and pulmonary gas exchange was measured after 10 minutes at rest and after eight minutes standing upright in 16 patients with HVS and 13healthy control subjects. In patients with HVS arterial blood samples were also drawn at rest and in the standing position.
RESULTS—At rest the variables of respiratory gas exchange did not differ significantly between the groups. As a response to standing, minute ventilation increased in both study groups but significantly more in the patients with HVS (mean difference 5.4 l/min (95% CI 1.1 to 9.6)). The changes in end tidal CO2 fraction (FETCO2) and in ventilatory equivalents for oxygen (V̇E/V̇O2) and for CO2 (V̇E/V̇CO2) during the orthostatic test were also significantly larger in patients with HVS than in healthy controls. During standing FETCO2 was significantly lower (mean difference -1.1 kPa; 95% CI -1.5 to -0.6) and V̇E/V̇O2 (mean difference 18.4; 95% CI 7.7to 29.0) and V̇E/V̇CO2 (mean difference 11.7; 95% CI 4.8 to 18.6) were significantly higher in HVS patients than in healthy controls. By using the cut off level of 4% for FETCO2 the sensitivity and specificity of the test to discriminate HVS were 87% and 77%, respectively, and by using the cut off level of 37 for V̇E/V̇O2 they were 93% and 100%, respectively. In the HVS patients arterial PCO2 and FETCO2 were closely correlated during the orthostatic test (r = 0.93, p<0.0001).
CONCLUSIONS—As a response to change in body position from supine to standing, patients with HVS have an accentuated increase in ventilation which distinguishes them from healthy subjects. These findings suggest that non-invasive measurements of pulmonary gas exchange during orthostatic tests are useful in the clinical evaluation of patients with hyperventilation disorders.


doi:10.1136/thorax.55.4.295
PMCID: PMC1745734  PMID: 10722769

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