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Biomedical subjects

Louis-Philippe Boulet

Publications and source records attributed to Louis-Philippe Boulet.

At least 37 records · Page 2Linked to original sources
PubMed2005

The CONCEPT trial: a 1-year, multicenter, randomized,double-blind, double-dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/budesonide in adults with persistent asthma.

BACKGROUND: A patient-driven, adjustable maintenance dosing (AMD) approach to asthma therapy, in which the dose is adjusted by patients according to the severity of their symptoms, has recently been compared with fixed-dose therapy in open-label studies. OBJECTIVE: This study used a double-blind, double-dummy design to compare the efficacy of 2 treatment approaches: stable dosing of salmeterol/fluticasone propionate (SAL/FP) and AMD of formoterol/budesonide (FOR/BUD). METHODS: This was a 1-year, multicenter, randomized, double-blind, double-dummy study in adult patients with symptomatic asthma that was not controlled by therapy with 200 to 500 microg/d inhaled corticosteroid (ICS) plus a long-acting beta2 agonist, or with >500 to 1000 microg/d ICS alone. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 microg BID or 2 inhalations of FOR/BUD 6/200 microg BID, both delivered via dry powder inhaler devices. After 4 weeks of stable dosing in both groups, eligible patients continued the study for an additional 48 weeks, receiving either a stable dose of SAL/FP or AMD of FOR/BUD. According to the AMD treatment plan, patients initially halved their dose and subsequently stepped up or down as indicated by the presence or absence of nocturnal awakenings due to asthma, frequency of rescue medication use, and changes in morning peak expiratory flow (PEF). The primary end point was the percentage of symptom-free days. Other parameters included daily asthma symptom scores, morning PEF, percentage of days free of rescue medication use, daily rescue medication use, percentage of nighttime awakenings due to asthma, percentage of weeks with well-controlled asthma, and number of exacerbations requiring oral corticosteroids or emergency department (ED) visits/hospitalizations. Tolerability was assessed in terms of adverse events spontaneously reported or elicited at clinic visits. RESULTS: The intent-to-treat population comprised 688 patients (344 per treatment arm) with a mean age of 45 years and a mean baseline forced expiratory volume in 1 second 81% of the predicted normal value. After 4 weeks' stable dosing, 581 patients (295 SAL/FP, 286 FOR/BUD) continued beyond visit 3 into the remaining 48-week treatment period. Over weeks 1 through 52, patients receiving stable dosing of SAL/FP had a significantly greater percentage of symptom-free days compared with those receiving AMD of FOR/BUD (median, 58.8% vs 52.1%, respectively; P = 0.034). The incidence of asthma exacerbations requiring oral steroids or an ED visit/hospitalization was 47% lower with SAL/FP compared with FOR/BUD (adjusted annual mean rate, 0.18 vs 0.33; P = 0.008). During weeks 5 through 52, patients in the FOR/BUD AMD group used a mean of 1.8 inhalations/d (equivalent to BUD 360 microg/d), and 235 (82.2%) patients stepped down to 1 inhalation/d. Mean (SD) daily ICS exposure over 52 weeks was 463 (81) microg FP and 480 (238) microg BUD in the respective treatment arms. CONCLUSIONS: In this adult population with persistent asthma, stable dosing of SAL/FP 50/250 microg BID resulted in significantly greater increases in symptom-free days, days free of rescue medication, and morning PEE, as well as almost halving the exacerbation rate, compared with AMD of FOR/BUD 6/200 microg. The results suggest that there is a minimum daily amount of maintenance therapy necessary to prevent exacerbations in adults with persistent asthma.

Adult↗
PubMed2005

Deep inspiration avoidance and airway response to methacholine: Influence of body mass index.

OBJECTIVE: To evaluate the effects of deep inspiration avoidance response to methacholine inhalation in 23 nonobese (body mass index between 18 kg/m2 and 30 kg/m2) and 27 obese (body mass index 30 kg/m2 or greater), nonatopic, nonasthmatic normal subjects. METHODS: Each subject had four methacholine challenges. In tests A and B, the first postmethacholine forced expiratory volume in 1 s (FEV1) was measured at 30 s and 3 min postinhalation, respectively; tests C and D were single-dose tests (using the final dose of test B), with the first postmethacholine FEV1 being obtained at 3 min, without (test C) or with (test D) 20 min of deep inspiration avoidance before inhalation. RESULTS: The mean provocative concentrations inducing a 20% fall in FEV1 on tests A and B were 80.6 mg/mL and 28.5 mg/mL (P<0.0001) in nonobese subjects, respectively, and 56.3 mg/mL and 21.5 mg/mL (P<0.0001) in obese subjects, respectively. No significant differences were observed in test A or B between control and obese subjects. Mean falls in FEV1 for tests C and D were 20.3% and 40.0% (P=0.0003) in nonobese subjects, respectively, and 18.5% and 23.6% (P>0.05) in obese subjects, respectively. CONCLUSIONS: As previously observed in patients with asthma, the present study found that nonasthmatic obese subjects had no increase in the fall in FEV1 after deep inspiration avoidance before methacholine, whereas nonobese subjects did, suggesting that obesity alters airway function. No significant changes were found between groups for symptom perception.

Adult↗
PubMed2005

Efficacy and safety of mometasone furoate administered once-daily in the evening in patients with persistent asthma dependent on inhaled corticosteroids.

BACKGROUND: Once-daily dosing with an inhaled corticosteroid (ICS) may simplify asthma management and improve patient compliance. Since asthma is frequently worse at night, evening dosing appears to be a more obvious choice to accommodate the chronobiology of asthma than morning dosing. OBJECTIVE: The primary study objective was to compare the efficacy and safety of mometasone furoate (MF) dry powder inhaler (MF-DPI) 400 microg qd PM (one 400 microg inhalation) with placebo for the treatment of asthma in patients previously dependent on twice a day (bid, bis in die) ICS therapy. We also compared different regimens of MF-DPI with each other and with placebo. METHODS: This 12-week, multicenter, double-blind, placebo-controlled study evaluated lung function and asthma symptoms in 400 subjects with persistent asthma randomized to MF-DPI 200 microg qd (once a day, quaque die) PM, 400 microg qd PM as one inhalation from a 400 microg device, 400 microg qd PM as two inhalations from a 200 microg device, 200 microg twice daily (bid), or placebo. Evening doses were to be taken in the late afternoon or early evening, preferably before dinner time. RESULTS: Mean changes from baseline at endpoint in FEV1 (forced expiratory volume in 1 s) were similar for MF-DPI 400 microg qd PM (one inhalation; 0.41 L), MF-DPI 400 microg qd PM (2 inhalations; 0.49 L), MF-DPI 200 microg qd PM (0.41 L), and MF-DPI 200 microg bid (0.51 L); and all were significantly improved compared with placebo (0.16 L; p < 0.001). Secondary efficacy variables, including nocturnal awakenings and use of rescue albuterol, were also significantly improved with MF-DPI treatment compared with placebo. All treatments were generally safe and well tolerated, with adverse events of mild to moderate severity. CONCLUSIONS: Once-daily evening dosing of MF-DPI at doses of 400 and 200 microg restored lung function and improved nocturnal and daytime symptom control in subjects with asthma previously dependent on bid ICS therapy. Comparable effectiveness of a total daily dose of 400 microg was demonstrated between once daily in the evening and twice-daily administration. The results also confirm the effectiveness of MF-DPI 200 microg qd PM, the lowest dose studied.

Adolescent↗
PubMed2005

Deep inspiration avoidance and methacholine response in normal subjects and patients with asthma.

BACKGROUND: Deep inspiration (DI) avoidance and time intervals between inhalation and measurement of FEV1 may influence methacholine challenges. OBJECTIVES: (1) To compare the degree of airway response to methacholine when the initial FEV1 measurements are obtained either 30 s or 3 min after inhalation, (2) to evaluate a simplified method to study the influence of DI avoidance before inhalation on the fall in FEV1, and (3) to determine if methacholine has a cumulative effect. PARTICIPANTS/METHODS: Twenty-five patients with asthma and 21 normal subjects without asthma. Four methacholine inhalation tests (MITs) were performed: two standard tidal-breathing MITs, with the first FEV1 measured 30 s (test A) and 3 min (test B) after the end of inhalation; a single-dose MIT, using the last concentration from test B, with no control of DI and the first FEV1 obtained 3 min after inhalation (test C); and an identical single-dose MIT preceded by 20-min of DI avoidance (test D). We compared the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from tests A and B (aim 1), the percentage fall in FEV1 from tests C and D (aim 2), and the percentage fall in FEV1 from tests B and C (aim 3). RESULTS: Mean PC20 values from tests A and B were 1.5 mg/mL and 1.0 mg/mL (p = 0.002) in patients with asthma, and 69.8 mg/mL and 29.9 mg/mL (p < 0.0001) in control subjects, respectively. The mean falls in FEV1 for tests C and D were 22.0% and 24.5% (p > 0.05) in patients with asthma, and 22.1% and 38.9% (p = 0.0005) in control subjects, respectively. The mean falls in FEV2 for tests B and C were 30.2% and 22.0% (p = 0.01) in patients with asthma, and 27.5% and 22.1% (p > 0.05) in control subjects, respectively. CONCLUSIONS: In both groups, the longer the time interval between the end of inhalation and the first FEV2 measurement, the greater the fall in FEV2 (lower PC20). DI avoidance before inhalation does not enhance the fall in FEV2 in subjects with asthma, while it does in control subjects. Methacholine has a slight cumulative effect that is significant in patients with asthma (p = 0.007).

Adolescent↗
PubMed2005

Optimization of the conditions for preservation of induced sputum: influence of freezing on cellular analysis.

BACKGROUND: Induced sputum (IS) analysis is a noninvasive, valid, and reproducible method for evaluating airway inflammation. It has been suggested that freezing of IS samples in order to delay analysis is feasible. However, the optimal conditions for preservation of IS samples have not been determined. OBJECTIVES: To determine optimal freezing conditions of IS samples, ensuring adequate specimen quality for assessment of cell viability, total cell count, and differential cell count. SUBJECTS AND METHODS: Twenty-one subjects were enrolled: 6 healthy control subjects, 5 patients with allergic rhinitis, 5 patients with mild asthma, and 5 patients with severe asthma. Each came to the laboratory once for IS sampling. Cell plugs were homogenized with dithiothreitol and separated into 12 aliquots. Viability and total and differential cell counts were determined for each aliquot. Bovine serum albumin (BSA) with dimethylsulfoxide (DMSO) was added to half of the aliquots, and fetal bovine serum (FBS) with DMSO was added to the other half. One half of the aliquots containing BSA or FBS were frozen at -20 degrees C, and the other half were frozen at - 80 degrees C. After 3, 7, or 10 days, samples were thawed and total cell counts, viability, and differential cell counts were assessed. RESULTS: Slide quality and total cell counts did not vary significantly according to freezing duration, temperature, or medium when compared to nonfrozen control samples. With FBS at -80 degrees C, cell viability did not vary significantly between control samples and freezing for 3, 7, and 10 days (59% vs 54%, 59% vs 54%, and 58% vs 54%, respectively; p > 0.05), whereas every other condition showed a significant decrease. Freezing did not affect the eosinophil percentage significantly. CONCLUSION: Freezing of IS samples in FBS with DMSO at - 80 degrees C allows adequate preservation of IS specimens. Samples can be kept for at least 10 days in those conditions without significantly altering total cell counts, viability, and eosinophil percentage.

Adolescent↗
PubMed2005

Lower airway inflammatory responses to high-intensity training in athletes.

PURPOSE: There is an increased prevalence of asthma and airway hyperresponsiveness in elite athletes, particularly in swimmers. High intensity exercise may induce airway inflammation and subsequent remodelling in these subjects. Our aim was to evaluate the effects of high-intensity training on induced-sputum cell populations in elite athletes. METHODS: Swimmers and runners with hyperresponsive airways (SH and RH), defined by a provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20) <16 mg/ml or with normoresponsive airways (PC20 > 16 mg/ml; SN, RN) to methacholine were enrolled. The mean PC20 was 2.27 mg/ml in SH (n=12), 32.2 in SN (n=10), 3.25 in RH (n=10) and 41.5 in RN (n=13). All athletes had two induced sputum analyses at one- to two-week intervals in random order: after a period of 72 hours without training, 24 hours after a training session. RESULTS: PC20 was unchanged after training. The median % neutrophils and eosinophils in groups SH, SN, RH, and RN, respectively, were 26.5-1.6, 8.6-0.3, 28.0-0.03 and 25.5-0.1 before and 45.0-0.5, 31.1-0.4, 54.0-0.6 and 48.3-0.3 after training. While the magnitude of the increase in neutrophils was similar for all groups, it reached statistical significance (pre-post-training) only in the SH group (P = 0.039). CONCLUSION: A one-hour session of high-intensity training was associated with an increase in airway neutrophils among hyperresponsive swimmer athletes, while airway responsiveness remained unchanged in all groups.

Adult↗
PubMed2004

Tissue-engineered human asthmatic bronchial equivalents.

The isolation of human bronchial epithelial (HBEC) and fibroblastic cells (HBFC) from biopsies of asthmatic and non-asthmatic volunteers provided unique cellular materials to be used for the production of bioengineered bronchial equivalents (BE) in vitro. The HBEC are grown on a mesenchymal layer seeded with HBFC and the BE can be maintained for at least 15 days in culture. Under the BE culture conditions established previously, HBEC undergo differentiation into ciliated and goblet cells, within a pseudostratified organization comparable to human bronchi. We published previously the results from histologic and functional analyses of such BE produced exclusively using non-asthmatic HBEC and HBFC. We report here the comparative analyses of BE produced with non-asthmatic and asthmatic living HBEC and HBFC (naBE and aBE, respectively). Our data indicated that all asthmatic HBEC populations grown on a mesenchymal layer, containing non-asthmatic HBFC, slowly reached a confluent state but then detached from the matrix upon culture time. These BE appear to be very good models to study the mechanisms involved in asthma in vitro.

Adult↗
PubMed2004

Physicians' assessment of asthma control in low vs. high asthma-related morbidity regions.

OBJECTIVES: To analyze physician-assessed asthma control and care compared with current guidelines criteria, in a cohort of patients from a high (HMR) vs. low asthma-related morbidity region (LMR), as determined by a large-scale populational survey (asthma cartography). DESIGN: Analysis of questionnaires provided by 47 primary care physicians and asthmatic patients (HMR: 74; LMR: 73). RESULTS: Asthma control was often suboptimal in both regions. In both regions, asthma control, the pattern of prescriptions for asthma, patient compliance, and referral for asthma education were similar; 32% of patients had been referred for asthma education, whereas 65% wanted to know more about their asthma. CONCLUSIONS: Results of regional/local cohort studies differ from those of a "population cartography," the former probably more likely reflecting individual medical practices of physicians interested in taking part in such studies.

Adult↗
PubMed2004

Once-daily inhaled corticosteroids for the treatment of asthma.

PURPOSE OF REVIEW: Inhaled corticosteroids (ICS) are the mainstay of asthma therapy. Although compliance to this type of medication is often suboptimal and once-daily dosing can help to improve adherence to the treatment, the clinical implications of such a mode of administration should be determined. RECENT FINDINGS: This review summarizes the recent studies on comparative efficacy of once-versus twice-daily administration of ICS, in light of previous reports. SUMMARY: Although twice-daily administration of ICS is often better to optimize asthma parameters, in many patients, asthma can be sufficiently controlled by a once-daily regimen of most ICS. An increased frequency of dosing seems preferable if asthma becomes uncontrolled or is severe, although this requires further study. A therapeutic trial should, however, be done to ensure that asthma control is adequate. Comparative long-term effects of such a strategy on inflammatory and remodeling parameters remain to be determined, as does the proportion of patients who can adequately control their asthma with once-daily administration of the various ICS available.

Androstadienes↗
PubMed2004

Comparative prevalence of asthma in different groups of athletes: a survey.

BACKGROUND: The type of air predominantly inhaled during training seems to play an important role in the development of airway hyperresponsiveness in athletes; however, this factor has not been evaluated for asthma. OBJECTIVE AND PATIENTS: To compare the prevalence of self-reported and/or physician-diagnosed asthma among four groups of athletes categorized according to the type of air predominantly inhaled during training: cold air (n=176), dry air (n=384), humid air (n=95), and mixed dry and humid air (n=43). METHOD: Self-administrated questionnaires were used. RESULTS: One hundred seven (15.3%) of the 698 athletes reported having asthma; of these 107 athletes, 92 had physician-diagnosed asthma. No significant differences were found for the prevalence of asthma: 15.9% (cold air), 15.4% (dry air), 12.6% (humid air) and 18.6% (mixed dry and humid air), respectively (P>0.05). Furthermore, no significant differences were observed among the groups for the prevalence of confirmed atopy, cold/flu or respiratory infections (all P>0.05), except for the prevalence of hay fever, which was significantly lower among athletes of the dry air group (P=0.04). Athletes having a first-degree relative with asthma did not have a higher prevalence of asthma than those who did not (P>0.05). CONCLUSION: The prevalence of asthma was not significantly different among the four groups of athletes and it was not associated with a family history of asthma.

Adolescent↗
PubMed2004

Cartography of emergency department visits for asthma - targeting high-morbidity populations.

BACKGROUND: Asthma education should be offered with priority to populations with the highest asthma-related morbidity. In the present study, the aim was to identify populations with high-morbidity for asthma from the Quebec Health Insurance Board Registry, a large administrative database, to help the Quebec Asthma and Chronic Obstructive Pulmonary Disease Network target its interventions. METHODS: All emergency department (ED) visits for asthma were analyzed over a one-year period, considering individual and medical variables. Age- and sex-adjusted rates, as well as standardized rate ratios related to the overall Quebec rate, among persons zero to four years of age and five to 44 years of age were determined for 15 regions and 163 areas served by Centres Locaux de Services Communautaires (CLSC). The areas with rates 50% to 300% higher (P<0.01) than the provincial rate were defined as high-morbidity areas. Maps of all CLSC areas were generated for the above parameters. RESULTS: There were 102,551 ED visits recorded for asthma, of which more than 40% were revisits. Twenty-one CLSCs and 32 CLSCs were high-morbidity areas for the zero to four years age group and five to 44 years age group, respectively. For the most part, the high-morbidity areas were located in the south-central region of Quebec. Only 47% of asthmatic patients seen in ED had also seen a physician in ambulatory care. CONCLUSION: The data suggest that a significant portion of the population seeking care at the ED is undiagnosed and undertreated. A map of high-morbidity areas that could help target interventions to improve asthma care and outcomes is proposed.

Adolescent↗
PubMed2004

Safety and efficacy of HFA-134a beclomethasone dipropionate extra-fine aerosol over six months.

OBJECTIVE: To compare the systemic safety and efficacy of hydrofluoroalkane beclomethasone dipropionate (HFA-BDP) extra-fine aerosol 800 microg/day with chlorofluorocarbon (CFC)-BDP 1500 microg/day. DESIGN: Six-month, randomized, parallel-group, double-blind, double-dummy study. PATIENTS: Patients (n=141) with moderate to severe asthma adequately controlled by CFC-BDP 1000 microg/day to 2000 microg/day. INTERVENTIONS: Patients received CFC-BDP 1500 microg/day during a two-week run-in period and were then randomized to either HFA-BDP (n=70) or CFC-BDP (n=71). RESULTS: Similar proportions of HFA-BDP and CFC-BDP patients had a 24 h urinary free cortisol values below the reference range at month 6 (15% versus 25%, P=0.35). Measures of adrenocorticotrophic hormone stimulation and morning plasma cortisol levels were also similar in each group. The frequency of skin bruising and oral candidiasis was low for both treatments. No change in intraocular pressure was reported for either treatment. Pulmonary function was similar in both groups; however, the onset of the first asthma exacerbation or increased asthma symptoms tended to be earlier for CFC-BDP than for HFA-BDP (P=0.076); 27% of CFC-BDP patients reported increased asthma symptoms, compared with 14% of HFA-BDP patients (P=0.095). CONCLUSIONS: HFA-BDP 800 microg/day has a systemic adverse event profile comparable to that of CFC-BDP 1500 microg/day, and further control of asthma symptoms may be achieved after a switch from CFC-BDP 1500 microg/day to HFA-BDP 800 microg/day.

Administration, Inhalation↗
PubMed2004

Evaluation of a program aimed at increasing referrals for asthma education of patients consulting at the emergency department for acute asthma.

BACKGROUND: Emergency department (ED) visits for asthma may reflect poor asthma control, often due to insufficient asthma education and medical follow-up. However, few patients consulting an ED for asthma are referred for education. AIMS: To describe a model for automatic referral to educational interventions targeting patients consulting at the ED for acute asthma, to demonstrate how this model can be integrated into current care, and to increase referrals for asthma education. METHODS: The program combines a short ED-based educational intervention with the goal of motivating patients and their families to pursue an educational program with an automatic referral to an asthma education center (AEC) after agreement with ED physicians. The program was implemented in nine acute care centers with a high number of ED visits for asthma. The main study parameter was the number of patients referred to an AEC after 4 months of program implementation, as compared with 4 months before. In addition, we assessed potential barriers to successfully establishing the program. RESULTS: In the first 4 months of the program, 1,104 patients were referred to an AEC, compared with 110 for the same period the year before; 106 patients (15%) patients could not be contacted, 114 patients (16.1%) refused the intervention, 488 patients (68.9%) made appointments, and 346 patients (48.9%, or 72.8% of scheduled patients) honored their appointments. CONCLUSION: We describe a model of educational intervention for asthmatic patients consulting at the ED. We found that ED professionals can motivate patients to attend an asthma education program and that an automatic referral process is well accepted by ED staff. Such intervention can help to reduce asthma-related morbidity, but local barriers to implementation of such program should be addressed.

Acute Disease↗
PubMed2003

Physiopathology of airway hyperresponsiveness.

Airway hyperresponsiveness (AHR), the tendency of the airways to narrow too much and too easily in response to various stimuli, is a universal feature of asthma, although it is not exclusive to this disease. Airway responsiveness shows a unimodal distribution in the general population and might vary with time, increasing after exposure to allergens, industrial substances, or infectious agents in predisposed individuals, or decreasing for variable time periods after environmental or pharmacologic interventions. Airway inflammation and structural airway changes can lead to this heightened airway response, but the mechanisms by which they modify airway function are still unclear. They might be associated with increased contractile properties of the airways--from an increase in contractile elements, a change in smooth muscle mechanical properties, or a reduction of forces opposing bronchoconstriction, such as reduced airway-parenchymal interdependence. Other factors, such as neurohumoral influences and "geometric factors" (eg, airway caliber), can modulate the degree of AHR.

Asthma↗
PubMed2003

Prevalence of respiratory symptoms in an athlete population.

This study aimed to look at the prevalence and type of respiratory symptoms experienced by athletes and to assess the possible influence on the perception of symptoms of training duration and environment. A group of 698 athletes (107 with diagnosed or self-reported asthma) filled out a questionnaire on their respiratory condition. They exercised either in cold air (n = 176), dry air (n = 384), humid air (n = 95) or mixed dry and humid air (n = 43). Past exercise-related symptoms reported by athletes were breathlessness (48.7%), phlegm production (22.8%), wheezing (15.6%), cough (15.2%), and chest tightness (7.4%). Only 25% of asthmatic athletes reported having current exercise-induced symptoms of breathlessness, 21.7%, wheezing and 17.4%, chest tightness; current exercise-induced symptoms of breathlessness, wheezing or chest tightness were also reported, respectively, in 38.9%, 3.6% and 2.7% of athletes without a diagnosis of asthma. The perception of exercise-induced symptoms was not influenced by the duration of training or environment. In conclusion, (1) a minority of asthmatic athletes report troublesome respiratory symptoms with exercise, (2) breathlessness is not more frequently reported in asthmatic athletes than in those without such diagnosis while cough and wheezing are more common in asthmatic subjects and (3) the prevalence of respiratory symptoms is independent of training environment and duration of training.

Adult↗