RESUMEN
BACKGROUND: In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it. METHODS: We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster(®), Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), "top responders", were then compared with those below the 25th percentile (n = 15) "poor responders". RESULTS: On average, the 59 patients completing the study (mean age ± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P < 0.001), but not in the inflammatory indicators (EBT, CRP and Eos). However, when comparing the "top responders" with the "poor responders", significant improvement in these inflammatory indicators was observed: EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[°C] to 33.57 ± 0.33, P = 0.003, Eos in blood fell from 381.7 ± 91.2 [cells/µL] to 244.2 ± 43.2, P = 0.02. Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders (Mann-Whitney test, P = 0.04). CONCLUSION: Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation. These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping. Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment. However, improved compliance due to the "promise of a new drug" effect should also be considered as contributing to the treatment results.
Asunto(s)
Antiasmáticos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Administración por Inhalación , Adulto , Albuterol/administración & dosificación , Albuterol/análogos & derivados , Albuterol/uso terapéutico , Androstadienos/administración & dosificación , Androstadienos/uso terapéutico , Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/fisiopatología , Beclometasona/administración & dosificación , Beclometasona/uso terapéutico , Broncodilatadores/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Proteína C-Reactiva/metabolismo , Combinación de Medicamentos , Etanolaminas/administración & dosificación , Etanolaminas/uso terapéutico , Femenino , Combinación Fluticasona-Salmeterol , Fumarato de Formoterol , Humanos , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Calidad de Vida , Espirometría , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
We report a patient with chronic obstructive pulmonary disease (COPD) in whom severe lung function disorders are combined with completely preserved exercise capacity. We assessed the exercise capacity of a 44-year-old man (height 155 cm, BMI 19.6 kg.m-2, FEV1%pred. = 30.9%, FRC%pred. = 158%, KCO%pred. = 46.2%, PaO2 = 64.0 mmHg, Medical Research Council Dyspnea scale = 1, Baseline Dyspnea Index = 10) by the 6-minute walking distance test (6MWD) and the symptom-limited cardiopulmonary exercise test (CPET) on a treadmill using the Bruce protocol. The patient was able to walk 667 meters in the test and achieved peak relative oxygen consumption (VO2/kg) of 21.9 mL.min-1.kg-1. We attribute the preserved exercise capacity of the patient to the combined beneficial effect of the following factors: 1. Efficient extraction of the hemoglobin-transported oxygen from the alveoli (P50 = 3.10 kPa). 2. Optimal right ventricle remodelling with mild hypertrophy, without dilatation and congestion. 3. Hypoxic normoxemia without polyglobulia, resulting in good rheologic properties of blood. 4. A preserved locomotory activity of the patient. Such a combination of severe lung function disorders with mildly pronounced dyspnea and preserved exercise capacity supports the concept that the function profile of COPD patients is multidimensional and therefore such patients should have a complete assessment of their disability condition.
Asunto(s)
Tolerancia al Ejercicio/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Adulto , Disnea/fisiopatología , Prueba de Esfuerzo , Humanos , Masculino , Consumo de OxígenoRESUMEN
The purpose of the present study was to investigate the correlation between dyspnea ratings and a large group of lung function parameters, and extract those factors that best reflect the functional profile of patients with COPD using factor analysis. Ninety nine patients with COPD in stable clinical condition (age 60 +/- 8 years, ATS score = 2.5 +/- 0.9, FEV1% pred. = 33 +/- 13%) were included in the study. The factor analysis of the results yielded 5 factors which accounted for 80.1% of the total variance of the changes. The highest coefficients found between the factors and the original group of variables after Varimax rotation are given in the following table: Factor 1: Oxygen-cost diagram: 0.92; ATS dyspnea score: -0.80; TL,CO/VA: 0.78; Factor 2: FEV1% pred.: 0.87; FEV1/VC%: 0.86; FEV1L: 0.79; Factor 3: MIF50% pred.: 0.85; FIV1% pred.: 0.76; PImax: 0.67; Factor 4: PaCO2: -0.81; SaO2: 0.77; Mean pulmonary arterial pressure: -0.67 Factor 5: Age: 0.88; Six minutes walk distance: -0.72 The factor analysis showed that the functional profile of COPD patients has several dimensions. Therefore, in order to have COPD comprehensively evaluated, assessment of dyspnea and the respective set of lung function parameters (exercise capacity, forced inspiration and pulmonary hemodynamics), should be included in the battery of tests, besides the conventional tests.