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Louis-Philippe Boulet

Publications and source records attributed to Louis-Philippe Boulet.

At least 19 recordsLinked to original sources

New insights into occupational asthma.

PURPOSE OF REVIEW: To examine recent publications on the types of agents involved in occupational asthma, the mechanisms by which they induce asthma, and how best to evaluate and treat workers suspected of this respiratory condition. RECENT FINDINGS: High rates of occupational asthma and inhalation accidents were found in workers in crafts and related occupations in the manufacturing industries, and in plant and machine operatives; cleaners and construction workers may also be at risk. Further data support a role for CD4 T cells in low-molecular-weight agent-induced asthma, such as with isocyanates, and neurogenic mechanisms may also be involved. The use of noninvasive measures of airway inflammation in the diagnosis and management of occupational asthma such as sputum eosinophils monitoring is promising, although this is less obvious for exhaled nitric oxide. Finally, the persistence of troublesome asthma even after withdrawal from relevant exposure has been re-emphasized and surveillance programs have been proposed. SUMMARY: Further data have been gathered on the prevalence of occupational asthma in various working populations, its mechanisms of development, the contribution of noninvasive measures of airway inflammation in the diagnosis and management of this condition, and its management and prevention.

Asthma↗

Safety and effectiveness of long-acting inhaled beta-agonist bronchodilators when taken with inhaled corticosteroids.

Long-acting beta-agonists are a pillar of therapy for many patients with asthma because they are the preferred add-on therapy to inhaled corticosteroids. However, a recent meta-analysis documented a substantial increase in severe exacerbations requiring hospital admission and life-threatening asthma exacerbations in patients treated with long-acting beta-agonists. A careful evaluation of this meta-analysis raises several concerns about its applicability to current practice. Pivotal trials evaluating the benefit of adding long-acting beta-agonists to inhaled corticosteroids were not included. The authors of the current paper call for physicians to continue their usual practice of using long-acting beta-agonists as adjunctive therapy, as well as for an independent meta-analysis of individual patients using inhaled corticosteroids and long-acting beta-agonists concomitantly.

Administration, Inhalation↗

The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies.

Sedentary lifestyles and increased pollution brought about by industrialization pose major challenges to the prevention of both obesity and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea and obesity hypoventilation syndrome. Obesity has emerged as an important risk factor for these respiratory diseases, and in many instances weight loss is associated with important symptomatic improvement. Moreover, obesity may influence the development and presentation of these diseases. In this article, we review the current understanding of the influence of obesity on chronic respiratory diseases and the clinical management of obesity concurrent with asthma, COPD, obstructive sleep apnea or obesity hypoventilation syndrome.

Asthma↗

The determinants of prevalence of health complaints among young competitive swimmers.

OBJECTIVES: Chloramines, which are produced by the reaction of chlorine with the organic matter present in indoor pools, are potential airway irritants in swimmers. The objective of this study was to compare the prevalence of health complaints of young swimmers and young indoor soccer players and to evaluate the relationship between chloramine concentrations and the athletes' health complaints. METHODS: Health complaints were first (Part 1) documented by questionnaire in 305 competitive swimmers and 499 indoor soccer players of the Québec City region (Canada). Then, (Part 2) health complaints were documented during five training sessions in 72 competitive swimmers in comparison to 73 soccer players. The chloramines in the swimming pool air and water were measured as well as the peak expiratory flow (PEF) before and after the training session. RESULTS: In Part 1, the swimmers reported more lower (adjusted OR: 1.5; IC95%= 1.0-2.2) and upper respiratory symptoms (adjusted OR: 3.7; IC95%= 2.4-5.8). In Part 2, the swimmers experienced more frequent lower (adjusted OR: 3.5; IC95%= 2.0-6.0) and upper respiratory symptoms (adjusted OR: 3.1; IC95%= 1.8-5.4). Overall, swimmers exposed to the highest levels of chloramines in the air and water had more respiratory complaints. CONCLUSIONS: Swimmers exposed to chlorination by-products in both the water and air of indoor swimming pools experience frequent respiratory symptoms that could potentially be reduced by limiting exposure to these products.

Adolescent↗

Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses.

RATIONALE: 1018 ISS is a synthetic oligonucleotide containing immunostimulatory CpG motifs. In animal studies, 1018 ISS effectively inhibited Th2-mediated lung inflammation, including eosinophil infiltration, and airway hyperresponsiveness. OBJECTIVES: To evaluate whether 1018 ISS has activity in subjects with allergic asthma. METHODS: Forty subjects (n = 21, 1018 ISS; n = 19, placebo) were enrolled in a randomized, double-blind, placebo-controlled, parallel-group study to examine safety, pharmacologic activity, and efficacy of 1018 ISS on allergen-induced airway responses. Subjects received 36 mg of 1018 ISS or placebo by nebulization weekly for 4 wk. MEASUREMENTS: Allergen inhalation challenge was performed 24 h after the 2nd and 4th doses to measure the early and late fall in FEV(1). Sputum cells and peripheral blood mononuclear cells were collected before and after dosing, and gene expression was measured by quantitative polymerase chain reaction. MAIN RESULTS: Treatment with 1018 ISS significantly increased expression of interferon (IFN)-gamma and IFN-inducible genes, such as IFN-gamma-inducible 10 kD protein (IP10), monokine induced by IFN-gamma (MIG), IFN-stimulated gene (ISG)-54, monocyte chemotactic protein (MCP)-1, and MCP-2 from cells collected postdose (p < 0.05). There was no attenuation of the early or late decrease in FEV(1) after 1018 ISS compared with placebo, nor a reduction in allergen-induced sputum eosinophils or Th2-related gene expression measured in sputum cells. CONCLUSIONS: This study demonstrated that 1018 ISS is safe and pharmacologically active in the respiratory tract of asthmatics but, at this dose regimen, did not inhibit a fall in FEV(1) or other key features of the response to inhaled allergen challenge. This suggests that induction of IFN and IFN-inducible genes alone is not sufficient to inhibit allergen-induced responses in asthmatic subjects.

Adjuvants, Immunologic↗

Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes.

BACKGROUND: Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. OBJECTIVE: To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA. METHODS: Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. RESULTS: No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). CONCLUSIONS: Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.

Aged↗

A fast, simple, and inexpensive method to collect exhaled breath condensate for pH determination.

BACKGROUND: Exhaled breath condensate (EBC) analysis is a noninvasive method for assessing lower airway inflammation. Various methods of collecting EBC have been described. However, they are often time-consuming or involve expensive equipment. OBJECTIVE: To evaluate the efficiency and repeatability of a simple, fast, and inexpensive method of EBC collection for pH determination. METHODS: Twenty-four mild asthmatic patients, 18 moderate-to-severe asthmatic patients, and 26 controls were asked to slowly exhale for 45 seconds into a -80 degrees C cooled metal cylinder covered with protective rubber and attached to a piece of tubing. The EBC was collected using a syringe's plunger. The groups were compared regarding EBC pH. Reproducibility tests were also performed. Induced sputum samples were obtained for inflammatory cell counts. RESULTS: We obtained approximately 50 microL of EBC for pH determination. Mild asthmatic patients had lower mean +/- SD pH values than controls (5.97 +/- 0.48 vs 6.36 +/- 0.34; P = .008), and corticosteroid-treated, moderate-to-severe asthmatic patients had mean +/- SD pH values similar to controls (6.23 +/- 0.38; P > .05). Mean +/- SD sputum eosinophil percentages were higher in both asthmatic groups than in controls (3.42% +/- 5.37% and 4.14% +/- 4.98% vs 0.04% +/- 0.12%; P < .001) and were not correlated with pH values in all groups. The mean intraday coefficient of variation for the method was 4.8% (range, 0.9%-8.8%). No correlation was found in all groups between sputum neutrophils and pH. CONCLUSIONS: We developed a useful device for collecting EBC for pH evaluation that could provide an alternative to other methods when pH is the main variable evaluated.

Adolescent↗

Algae-induced occupational asthma in a thalassotherapist.

BACKGROUND: Algae powders have been increasingly used in therapeutic preparations. Their potential as inducers of occupational asthma (OA), however, remains to be demonstrated. METHODS: A 33-year-old woman developed asthma following exposure to algae powder used for thalassotherapy. She had positive patch tests to nickel and cobalt in an evaluation for intermittent skin rash. At work, she had a normal forced expiratory flow in 1 s (FEV(1)) but moderate airway hyperresponsiveness. Bronchial provocation tests (BPT) were obtained. RESULTS: On BPT, an isolated early response was observed after a 1-min inhalation of dry algae powder, with a 50% fall in FEV(1) after exposure; the control BPT with lactose powder was negative. CONCLUSIONS: We report a case of algae-powder-induced OA. Such responses could be due to a sensitization to algae proteins or metal contaminants bioabsorbed by the vegetal particles.

Adult↗

Implementing practice guidelines: a workshop on guidelines dissemination and implementation with a focus on asthma and COPD.

The present supplement summarizes the proceedings of the symposium "Implementing practice guidelines: A workshop on guidelines dissemination and implementation with a focus on asthma and COPD", which took place in Quebec City, Quebec, from April 14 to 16, 2005. This international symposium was a joint initiative of the Laval University Office of Continuing Medical Education (Bureau de la Formation Médicale Continue), the Canadian Thoracic Society and the Canadian Network for Asthma Care, and was supported by many other organizations and by industrial partners. The objectives of this meeting were to examine the optimal implementation of practice guidelines, review current initiatives for the implementation of asthma and chronic obstructive pulmonary disease (COPD) guidelines in Canada and in the rest of the world, and develop an optimal strategy for future guideline implementation. An impressive group of scientists, physicians and other health care providers, as well as policy makers and representatives of patients' associations, the pharmaceutical industry, research and health networks, and communications specialists, conveyed their perspectives on how to achieve these goals. This important event provided a unique opportunity for all participants to discuss key issues in improving the care of patients with asthma and COPD. These two diseases are responsible for an enormous human and socioeconomic burden around the world. Many reports have indicated that current evidence-based guidelines are underused by physicians and others, and that there are many barriers to an effective translation of recommendations into day-to-day care. There is therefore a need to develop more effective ways to communicate key information to both caregivers and patients, and to promote appropriate health behaviours. This symposium contributed to the initiation of what could become the "Canadian Asthma and COPD Campaign", aimed at improving care and, hence, the quality of life of those suffering from these diseases. It is hoped that this event will be followed by other meetings that focus on how to improve the transfer of key recommendations from evidence-based guidelines into current care, and how to stimulate research to accomplish this.

Asthma↗

Future directions in the clinical management of cough: ACCP evidence-based clinical practice guidelines.

OBJECTIVES: To impart a call for further research into the identified domains of particular interest in the etiology, management, and treatment of cough. DESIGN/METHODOLOGY: A literature review was performed using the search term "cough" in PubMed between 1983 and 2004. The final draft of this guideline was reviewed, in addition to recent studies on cough, and suggestions provided by the authors were collated into a definitive inventory of specific areas in which the lack of quality evidence encumbered the development of clinically relevant evidence-based recommendations. RESULTS/CONCLUSIONS: Although our understanding of the causes and optimal management of chronic cough have significantly increased over the past 25 years, further research remains to be done on this common symptom. This is reflected by the generally low level of evidence for many of the recommendations in these guidelines. Research is particularly needed on the optimal treatment of postinfectious cough, how to distinguish acute bronchitis from other conditions, how to reliably diagnose and treat cough due to gastroesophageal reflux disease, clearly identifying a role for nonpharmacologic protussive treatment modalities in diseases associated with an increased production of bronchial secretions, determining how often cough in patients with interstitial lung disease is due to conditions other than these, establishing the spectrum and frequency of causes of chronic cough in the immunocompromised hosts, and better characterizing psychogenic cough. Further studies are also needed on methods for the assessment of cough, in particular, noninvasive measures of airway inflammation, and pharmacotherapy. It should be determined how often unexplained cough (previously referred to as idiopathic cough) is due to the use of non-evidence-based guidelines or to environmental causes, and assessed whether an empiric, integrative approach of diagnosing chronic cough leads to better outcomes, including cost-effectiveness, than routine testing. While much work has been done on chronic cough, we need studies on the spectrum and frequency of acute and subacute coughs.

Cough↗

Smoking and asthma: clinical and radiologic features, lung function, and airway inflammation.

Smoking may influence the type of airway inflammation observed in asthma and its response to therapy. More studies are needed on how smoking-induced changes in lung function/structure and airway inflammation may result in a change in clinical expression. We compared clinical, physiologic, radiologic, and airway inflammatory features of 22 smoking asthma patients (cigarette smoking history, 14.0 +/- 7.6 pack-years [mean +/- SD]) and 27 nonsmoking asthma patients. Mean age/duration of asthma of smoking and nonsmoking asthma patients were 31 years/14 years and 29 years/17 years, respectively. Quality of life, FEV(1), bronchodilator response, perception of bronchoconstriction, and methacholine responsiveness were similar in the two groups. Compared to nonsmoking asthma patients, smokers had more respiratory symptoms, a lower mean forced expiratory flow at 25 to 75% of FVC, FEV(1)/FVC ratio, and lung diffusion capacity, and a higher functional residual capacity. Induced-sputum neutrophil and bronchial cell counts were higher and exhaled breath condensate pH was more acidic in smoking asthma patients. On high-resolution CT, airway and parenchymal abnormalities were more common in smoking asthma patients than in nonsmokers. In conclusion, compared with nonsmoking asthma patients, smoking asthma patients have features similar to what could be found in early stages of COPD.

Adult↗

Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation.

In airway diseases such as asthma and COPD, specific structural changes may be observed, very likely secondary to an underlying inflammatory process. Although it is still controversial, airway remodeling may contribute to the development of these diseases and to their clinical expression and outcome. Airway remodeling has been described in asthma in various degrees of severity, and correlations have been found between such features as increase in subepithelial collagen or proteoglycan deposits and airway responsiveness. Although the clinical significance of airway remodeling remains a matter of debate, it has been suggested as a potential target for treatments aimed at reducing asthma severity, improving its control, and possibly preventing its development. To date, drugs used to treat airway diseases have a little influence on airway structural changes. More research should be done to identify key changes, valuable treatments, and proper interventional timing to counteract these changes. The potential of novel therapeutic agents to reverse or prevent airway remodeling is an exciting avenue and warrants further evaluation.

Adrenal Cortex Hormones↗

Montelukast treatment attenuates the increase in myofibroblasts following low-dose allergen challenge.

RATIONALE: Airway remodeling is believed to be important in the pathophysiology of asthma, and myofibroblasts are increased in the airways of asthmatic individuals 24 h after allergen challenge. Leukotriene receptor antagonists exert antiinflammatory activity in asthma, but it is unknown whether they influence indices of airway remodeling. In the present study, we evaluated the effect of montelukast on airway myofibroblasts following low-dose allergen challenge (LDAC). METHODS: Stable subjects with mild asthma were included in a two-center, randomized, parallel-group study. A 2-week run-in period was followed by LDAC and endobronchial biopsy. Subjects were then randomized to receive either montelukast, 10 mg/d, or placebo (n = 10 in each group) for 8 weeks in a double-blind manner; at the end of the treatment period, subjects underwent a second LDAC and endobronchial biopsy. The effect of treatment on myofibroblasts, fibroblasts, and inflammatory cells was examined using electron microscopy techniques. RESULTS: Treatment with montelukast showed no significant difference by comparison with placebo but did show a significant within-group treatment-related decrease in airway wall myofibroblasts not seen in the placebo group. In addition, the montelukast-treated group also showed a significant within-group reduction in lymphomononuclear cells and increased neutrophils. CONCLUSIONS: The results suggest that montelukast has an inhibitory effect on airway structural cells that play a key role in airway remodeling in allergic airway inflammation, and that montelukast may be a useful therapy to attenuate airway remodeling in asthma.

Acetates↗

Comparison of cell fixation methods of induced sputum specimens: an immunocytochemical analysis.

Induced sputum (IS) is a non-invasive method to evaluate airway inflammation. Various techniques are used to fix IS cells but their respective value has never been compared. We aimed to determine the best IS cell fixation technique for cellular markers staining. Cells were fixed using four methods: 1) periodate-paraformaldehyde-lysine (PLP)-sucrose, 2) paraformaldehyde 4% on slide and 3) in solution and 4) acetone-methanol. Analysis was based on percentage of positive cells compared to total cell counts stained by hematoxylin and quality of staining. Using PLP-sucrose resulted in a higher percentage of positive cells for CD3 and a better quality of staining. Acetone-methanol showed a lower percentage of positive cells for CD68 and a poor quality. PLP-sucrose gives the best results for the preservation of the studied cell markers and acetone-methanol the worst.

Adult↗

Comparative improvement of asthma symptoms and expiratory flows after corticosteroid treatment: a method to assess the effect of corticosteroids on large vs. small airways?

The magnitude of improvement of respiratory symptoms (RS) and expiratory flows (EF) following corticosteroid treatment may vary from one asthmatic patient to another. The distribution of ratio of improvement of the above parameters was assessed in 937 patients with asthma of variable severity who took part in three clinical trials comparing the effects of chlorofluorocarbon-propelled beclomethasone dipropionate (CFC-BDP) with similar (n:316) or half-doses (n:581) of extrafine hydrofluoroalkane-propelled (HFA-BDP) on asthma control. We calculated the ratio of improvement of shortness of breath, wheezing, sleep disturbance, cough, and chest tightness over the following physiological parameters: forced expiratory volume in 1s (FEV1), FEF(25/75%), morning peak expiratory flow, and FVC, from the baseline value to the last set of measures in the study, while on the study medication. We hypothesized that the ratio of RS/EF would have a normal distribution and would be higher with extrafine HFA-BDP compared with CFC-BDP, which has a larger particle size, when FEV1 is used, as it mostly assesses large airways. Ratios of improvement were normally distributed for both drugs and no significant shift in its distribution curve was found for HFA-BDP. The ratio of changes in FEF(25/75%)/FEV1 was similar in the two groups. In conclusion, the ratio of improvement of RS/EF is normally distributed over a narrow range, showing a generally good correlation between improvements in EF and symptoms in asthma; it was, however, similar for the two BDP molecules tested. This may suggest that this ratio is not useful for evaluating the effect of corticosteroids on small airways, or that extrafine HFA-BDP acts at the level of large- to moderate-caliber airways to produce most of its beneficial effect.

Administration, Inhalation↗

Clinical features and airway inflammation in mild asthma versus asymptomatic airway hyperresponsiveness.

RATIONALE: We still do not know why some subjects with airway hyperresponsiveness (AHR) experience no respiratory symptoms. OBJECTIVES: Our aim was to compare pulmonary function, perception of bronchoconstriction, and airway inflammation in atopic subjects with mild recently diagnosed (<5 years, n=30) or longer-standing (5 years or more, n=30) symptomatic asthma in comparison with atopic subjects with asymptomatic AHR (n=27). METHODS: All subjects had measurements of expiratory flows, PC(20) methacholine, perception of breathlessness and induced sputum cell differential, eosinophil cationic protein and alpha(2)-macroglobulin levels. RESULTS: Compared with the other groups, PC(20) was significantly lower in longer-standing asthma and perception score for breathlessness at 20% fall in FEV(1) was lower in asymptomatic subjects. Markers of airway inflammation were similar in all groups. There were no significant correlations between sputum eosinophils, alpha(2)-macroglobulin and/or eosinophil cationic protein levels and FEV(1), FVC or PC(20) in either group. CONCLUSION: Subjects with mild asthma or asymptomatic AHR are similar in regard to induced sputum markers of airway inflammation. Although perception of bronchoconstriction was slightly lower in asymptomatic subjects, additional factors are probably involved to explain why they report no respiratory symptoms. Further studies are needed to determine why these last are asymptomatic.

Adolescent↗