In 102 healthy Caucasians, 20–50 years old, we investigated the effect of anthropometrics on the 6-min walk test (6MWT), in order to provide reference values for walk distance (6MWD), oxygen ...saturation (SpO
2), pulse rate (PR), respiratory rate (RR), breathlessness perception (VAS) and for the walking distance and body weight product (
DW).
The mean 6MWD and
DW values were 593±57 and 638±44
m (
P<0.01) and 35,030±5306 and 48,882±6555
kg
m (
P<0.01), respectively for women and for men. While walking, SpO
2 remained unaltered and subjects reached 67±10% of their maximal predicted heart rate and a RR mean value of 19±4
bpm. VAS ratings were significantly higher in females as compared to males (24±15 vs. 18±5
mm,
P<0.05), however, when corrected for PR change while walking, they were not different. The equation by stepwise multiple regression analysis included height, age and gender for the 6MWD and accounted for 42% of the total variance.
This study confirms the relevant effect of anthropometrics on walking capacity and suggests that when rating dyspnea, the change in heart rate during walking should be considered.
Treatment guidelines recommend the regular use of inhaled corticosteroids for patients with mild persistent asthma. We investigated whether the symptom-driven use of a combination of beclomethasone ...dipropionate and albuterol (also known as salbutamol) in a single inhaler would be as effective as the regular use of inhaled beclomethasone and superior to the as-needed use of inhaled albuterol.
We conducted a 6-month, double-blind, double-dummy, randomized, parallel-group trial. After a 4-week run-in, patients with mild asthma were randomly assigned to receive one of four inhaled treatments: placebo twice daily plus 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler as needed (as-needed combination therapy); placebo twice daily plus 100 microg of albuterol as needed (as-needed albuterol therapy); 250 microg of beclomethasone twice daily and 100 microg of albuterol as needed (regular beclomethasone therapy); or 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler twice daily plus 100 microg of albuterol as needed (regular combination therapy). The primary outcome was the morning peak expiratory flow rate.
In 455 patients with mild asthma who had a forced expiratory volume in 1 second of 2.96 liters (88.36% of the predicted value), the morning peak expiratory flow rate during the last 2 weeks of the 6-month treatment was higher (P=0.04) and the number of exacerbations during the 6-month treatment was lower (P=0.002) in the as-needed combination therapy group than in the as-needed albuterol therapy group, but the values in the as-needed combination therapy group were not significantly different from those in the groups receiving regular beclomethasone therapy or regular combination therapy. The cumulative dose of inhaled beclomethasone was lower in the as-needed combination therapy group than in the groups receiving regular beclomethasone therapy or regular combination therapy (P<0.001 for both comparisons).
In patients with mild asthma, the symptom-driven use of inhaled beclomethasone (250 microg) and albuterol (100 microg) in a single inhaler is as effective as regular use of inhaled beclomethasone (250 microg twice daily) and is associated with a lower 6-month cumulative dose of the inhaled corticosteroid. (ClinicalTrials.gov number, NCT00382889 ClinicalTrials.gov.).
In recent years, there has been increased interest in the vascular component of airway remodelling in chronic bronchial inflammation, such as asthma and COPD, and in its role in the progression of ...disease. In particular, the bronchial mucosa in asthmatics is more vascularised, showing a higher number and dimension of vessels and vascular area. Recently, insight has been obtained regarding the pivotal role of vascular endothelial growth factor (VEGF) in promoting vascular remodelling and angiogenesis. Many studies, conducted on biopsies, induced sputum or BAL, have shown the involvement of VEGF and its receptors in the vascular remodelling processes. Presumably, the vascular component of airway remodelling is a complex multi-step phenomenon involving several mediators. Among the common asthma and COPD medications, only inhaled corticosteroids have demonstrated a real ability to reverse all aspects of vascular remodelling. The aim of this review was to analyze the morphological aspects of the vascular component of airway remodelling and the possible mechanisms involved in asthma and COPD. We also focused on the functional and therapeutic implications of the bronchial microvascular changes in asthma and COPD.
We investigated whether a relationship between small airways dysfunction and bronchial hyperresponsiveness (BHR), expressed both in terms of ease of airway narrowing and of excessive ...bronchoconstriction, could be demonstrated in asthma.
63 (36 F; mean age 42 yr ± 14) stable, mild-to-moderate asthmatic patients (FEV1 92% pred ±14; FEV1/FVC 75% ± 8) underwent the methacholine challenge test (MCT). The degree of BHR was expressed as PD20 (in μg) and as ∆FVC%. Peripheral airway resistance was measured pre- and post-MCT by impulse oscillometry system (IOS) and expressed as R5-R20 (in kPa sL-1).
All patients showed BHR to methacholine (PD20 < 1600 μg) with a PD20 geometric (95% CI) mean value of 181(132-249) μg and a ∆FVC% mean value of 13.6% ± 5.1, ranging 2.5 to 29.5%. 30 out of 63 patients had R5-R20 > 0.03 kPa sL-1 (>upper normal limit) and showed ∆FVC%, but not PD20 values significantly different from the 33 patients who had R5-R20 ≤ 0.03 kPa sL-1 (15.8% ± 4.6 vs 11.5% ± 4.8, p < 0.01 and 156(96-254) μg vs 207 (134-322) μg, p = 0.382). In addition, ∆FVC% values were significantly related to the corresponding pre- (r = 0.451, p < 0.001) and post-MCT (r = 0.376, p < 0.01) R5-R20 values.
Our results show that in asthmatic patients, small airway dysfunction, as assessed by IOS, is strictly associated to BHR, expressed as excessive bronchoconstriction, but not as ease of airway narrowing.
Physical deconditioning is involved in the impaired exercise tolerance of patients with multiple sclerosis (MS), but data on the effects of aerobic training (AT) in this population are scanty. The ...purpose of this study was to compare the effects of an 8-week AT program on exercise capacity-in terms of walking capacity and maximum exercise tolerance, as well as its effects on fatigue and health-related quality of life-as compared with neurological rehabilitation (NR) in subjects with MS.
Nineteen subjects (14 female, 5 male; mean age X+/-SD=41+/-8 years) with mild to moderate disability secondary to MS participated in a randomized crossover controlled study. Eleven subjects (8 female, 3 male; mean age X+/-SD=44+/-6 years) completed the study.
After AT, but not NR, the subjects' walking distances and speeds during a self-paced walk were significantly improved, as were their maximum work rate, peak oxygen uptake, and oxygen pulse during cardiopulmonary exercise tests. The increases in peak oxygen uptake and maximum work rate, but not in walking capacity, were significantly higher after AT, as compared with after NR. Additionally, the subjects who were most disabled tended to benefit more from AT. There were no differences between AT and NR in effects on fatigue, and the results showed that AT may have partially affected health-related quality of life.
The results suggest that AT is more effective than NR in improving maximum exercise tolerance and walking capacity in people with mild to moderate disability secondary to MS.
Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation ...and cardiovascular response to maximal exercise in COPD patients.
We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.
Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.
The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.
Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain ...about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy.
This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency.
Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events.
Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control.
clinicaltrials.gov NCT00497237.
Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular diseases, in particular systemic arterial hypertension. We postulated that intermittent nocturnal hypoxia in OSAS may be ...associated to decreased fractional exhaled nitric oxide (FENO) levels from distal airspaces.
Multiple flow rate measurements have been used to fractionate nitric oxide (NO) from alveolar and bronchial sources in 34 patients with OSAS, in 29 healthy control subjects, and in 8 hypertensive non-OSAS patients. The effect of 2 days of treatment with nasal continuous positive airway pressure (nCPAP) on FENO was examined in 18 patients with severe OSAS.
We found that the mean ± SE concentrations of exhaled NO at a rate of 50 mL/s was 21.8 ± 1.9 parts per billion (ppb) in patients with OSAS, 25.1 ± 3.3 ppb in healthy control subjects, and 15.4 ± 1.7 ppb in hypertensive control patients. The mean fractional alveolar NO concentration (CANO) in OSAS patients was significantly lower than that in control subjects (2.96 ± 0.48 vs 5.35 ± 0.83 ppb, respectively; p < 0.05). In addition, CANO values were significantly lower in OSAS patients with systemic hypertension compared to those in normotensive OSAS patients and hypertensive patients without OSAS. The mean values of CANO significantly improved after nCPAP therapy (2.67 ± 0.41 to 4.69 ± 0.74 nL/L, respectively; p = 0.01).
These findings suggest that alveolar FENO, and not bronchial FENO, is impaired in patients with OSAS and that this impairment is associated with an increased risk of hypertension. NO production within the alveolar space is modified by treatment with nCPAP.
Background There is increasing evidence to support a role for total mast cells (MCTOT ) in the vascular component of airway remodeling in asthma. On the contrary, up to now, no study has addressed ...the role of chymase-positive mast cells (MCTC ) in microvasculature changes. Objective We sought to assess the role of MCTC in the vascular component of airway remodeling in asthma. Methods We recruited 8 patients with mild-to-moderate asthma and 8 healthy volunteers as a control group. Fiberoptic bronchoscopy with endobronchial biopsy was successfully performed in all subjects. Immunostaining was performed for quantification of vessels, vascular endothelial growth factor (VEGF)–positive cells, MCTOT , and MCTC. Results Compared with those from healthy subjects, endobronchial biopsy specimens from asthmatic patients showed increased numbers of MCTOT and MCTC and VEGF+ cells ( P < .05). In asthmatic patients the number of vessels and the vascular area was also greater than in healthy subjects ( P < .05). Additionally, in asthmatic patients the number of MCTC was significantly related to the vascular area ( rs = 0.74, P < .01) and to the number of VEGF+ cells ( rs = 0.78, P < .01). Moreover, a colocalization study revealed that MCTC were a relevant cellular source of VEGF. Finally, a 6-week treatment with inhaled fluticasone propionate was able to reduce MCTC numbers. Conclusion MCTC can play a role in the vascular component of airway remodeling in asthma, possibly through induction of VEGF. Clinical implications Specific targeting of MCTC might be a tool for treating vascular remodeling in asthma.
In chronic obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), changes in bronchial microvasculature are present in response to inflammatory stimuli. ...Vascular changes may significantly contribute to airway wall remodelling. Angiogenesis and vascular leakage are prevalent in asthma, while vasodilation and vascular leakage dominate in COPD. An endothelial dysfunction may be present both in asthma and in COPD. Vascular changes may occur simultaneously with the thickening of the airway wall and the narrowing of the bronchial lumen. Consequently, pharmacological control of bronchial vascular remodelling may be crucial for symptom control in asthma and COPD. In asthmatic airways, inhaled steroids can downregulate vascular remodelling by acting on proangiogenic factors. Additionally, studies on combination therapy with long-acting β2-agonists and inhaled steroids have provided evidence of a possible synergistic action on components of vascular remodelling in asthma. In COPD, there is less experimental evidence on the effect of inhaled steroids on airway microvascular changes. Importantly, vascular endothelial growth factor (VEGF), the most specific growth factor for vascular endothelium, is crucially involved in the pathophysiology of airway vascular remodelling, both in asthma and COPD. The inhibition of VEGF and its receptor may be useful in the treatment of the vascular changes in the airway wall.
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