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Biomedical subjects

Yvon Cormier

Publications and source records attributed to Yvon Cormier.

17 recordsLinked to original sources

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the subject has been previously sensitized. The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 30:100,000 and HP accounted for less than 2% of these cases. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence respectively, using simple diagnostic criteria. Chest X-rays may be normal in active HP; High Resolution Computed Tomography is sensitive but not specific for the diagnosis of HP. The primary use of pulmonary function tests is to determine the physiologic abnormalities and the associated impairment. Despite the pitfalls of false positive and false negatives, antigen-specific IgG antibodies analysis can be useful as supportive evidence for HP. Bronchoalveolar lavage plays an important role in the investigation of patients suspected of having HP. A normal number of lymphocytes rules out all but residual disease. Surgical lung biopsy should be reserved for rare cases with puzzling clinical presentation or for verification the clinical diagnosis when the clinical course or response to therapy is unusual. Being an immune reaction in the lung, the most obvious treatment of HP is avoidance of contact with the offending antigen. Systemic corticosteroids represent the only reliable pharmacologic treatment of HP but do not alter the long-term outcome. The use of inhaled steroids is anecdotal. Treatment of chronic or residual disease is supportive.

Adult↗

Dimethyphenylpiperazinium, a nicotinic receptor agonist, downregulates inflammation in monocytes/macrophages through PI3K and PLC chronic activation.

Activation of nicotinic acetylcholine receptors (nAChRs) on inflammatory cells induces anti-inflammatory effects. The intracellular mechanisms that regulate this effect are still poorly understood. In neuronal cells, nAChRs are associated with phosphatidylinositol 3-kinase (PI3K). This enzyme, which can activate phospholipase C (PLC), is also present in monocytes. The aim of this study was to assess the role of these proteins in the signaling pathways involved in the anti-inflammatory effect of dimethylphenylpiperazinium (DMPP), a synthetic nAChR agonist, on monocytes and macrophages. The results indicate that PI3K is associated with alpha3, -4, and -5 nAChR subunits in monocytes. The PI3K inhibitors wortmannin and LY294002 abrogated the inhibitory effect of DMPP on LPS-induced TNF release by monocytes. Treatment with DMPP for 24 and 48 h provoked a mild PLC phosphorylation, which was blocked by the nAChR antagonist mecamylamine and reversed by PI3K inhibitors. Treatment of monocytes and alveolar macrophages with DMPP reduced the inositol 1,4,5-trisphosphate (IP3)-dependent intracellular calcium mobilization induced by platelet-activating factor (PAF), an effect that was reversed by mecamylamine in alveolar macrophages. DMPP did not have any effect on PAF receptor expression. DMPP also inhibited the thapsigargin-provoked calcium release, indicating that the endoplasmic reticulum calcium stores might be depleted by treatment with the nAChR agonist. Taken together, these results suggest that PI3K and PLC activation is involved in the anti-inflammatory effect of DMPP. PLC limited, but constant activation could induce, the depletion of intracellular calcium stores, leading to the anti-inflammatory effect of DMPP.

Anti-Inflammatory Agents↗

Adiposity affects human response to inhaled organic dust.

BACKGROUND: Swine containment facilities are often highly contaminated with organic dusts that often contain varying levels of endotoxins and other microbial products. This study was performed to evaluate the effect of obesity on the inflammatory response induced by chronic or acute exposure to swine confinement buildings (SCB). METHODS: Two separate studies were performed; Study I included 36 SCB long-time workers and a control group of 35 matched male hospital workers never exposed to SCB. In Study II, 14 naïve healthy young subjects (8 overweight and 6 lean) volunteered to be acutely exposed to a SCB environment for 5 hr. Markers of sub-clinical inflammation linked to obesity (C-reactive protein (CRP), interleukin 6 (IL-6)) or to active inflammation (soluble adhesion molecules, IL-8, TNF) were measured. RESULTS: In the first study, positive correlations were found between girth circumference and serum levels of IL-6 (r = 0.57, P = 0.0003) and CRP (r = 0.62, P < 0.0001) in the control group. These correlations were however blunted or lost in the SCB workers group who showed positive correlations between girth circumference and soluble l-selectin (r = 0.34, P = 0.04), TNFalpha (r = 0.37, P = 0.03), ICAM-1 (r = 0.61, P < 0.0001). In the second study involving acute SCB exposure of naïve volunteers, no significant differences were observed between normal weight and overweight subjects for white blood cells, nasal lavage cell counts, and IL-8 levels. However, higher levels of CRP, TNF, and IL-6 were detected in overweight volunteers compared to those who were lean. CONCLUSIONS: In pig farmers (Study I), environmentally induced chronic inflammation appears to blunt the sub-clinical inflammation linked to obesity, whereas in naïve volunteers of Study II, environmentally induced acute inflammation seems to have a potentiating effect on obesity-related inflammatory markers.

Administration, Inhalation↗

Hypersensitivity pneumonitis in a hardwood processing plant related to heavy mold exposure.

Two workers employed in a hardwood floor plant presented symptoms suggestive of hypersensitivity pneumonitis (HP). At that plant, kiln-dried wood often shows moldy growth and is subsequently brought inside for processing. This study evaluated the environment in attempt to identify the causative antigen and verify whether other workers of this and similar plants had or were at risk of developing HP. Dust from dust-removing systems and molds on the surface of wood planks were collected and air samples taken from a sister plant. Blood samples, spirometry, and symptoms' questionnaires were obtained from 11 co-workers. Dense Paecilomyces growth was observed on the surface of the dried processed wood in the index plant. This fungal genus was not detected in the sister plant. An additional worker had symptoms suggestive of HP, and his bronchoalveolar lavage revealed a lymphocytic alveolitis. The 3 confirmed cases of HP and the other 10 workers had positive specific IgG antibodies to Paecilomyces. We report 3 cases of HP out of 13 workers and a 100% sensitization to molds in workers of a hardwood processing plant. This rate is much higher than what is commonly seen in other environments associated with HP. The drying process is suspected of being responsible for the massive Paecilomyces contamination likely responsible for the HP.

Adult↗

Bioaerosols in peat moss processing plants.

Peat moss is organic matter colonized by large numbers of microorganisms. Storage prior to its processing may result in massive microbial growth. These biological contaminants can become airborne during processing. Our goals were (a) to evaluate concentrations of bioaerosols (inhalable dust, molds, bacteria) in peat moss processing plants that used dust removing systems, and (b) to evaluate the presence of these microorganisms in peat moss. Fourteen plants from Eastern Canada were visited; 3 plants operated all year (all-year mixing plants), and 11 plants functioned only during summer months (seasonal). Air samples were taken throughout the day at different work sites using IOM cassettes for inhalable dust and All-Glass Impinger-30 samplers and Andersen six-stage impactors for microorganisms. Samples of nonprocessed and bagged peat moss (solid material) were also taken and analyzed. A total of 25 work sites for air sampling and 33 solid material samples were analyzed. Air samples contained up to 441.7 mg/m3 of inhalable dust and up to 1.0 x 10(8) CFU/m3 mesophilic molds and 3.3 x 10(5) CFU/m3 bacteria. Seasonal plants were more contaminated with molds and dust than all-year mixing plants. Sieving sites were the most highly contaminated work sites. Airborne dust concentration was significantly correlated with molds and bacteria. Up to 3.8 x 10(7) CFU/g (dry weight) and 4.8 x 10(7) CFU/g (dry weight) molds and bacteria, respectively, were found in the solid material samples. Airborne contaminants did not correlate with solid material content. Despite the use of dust removing systems, peat moss processing plants contain very large amounts of microbially contaminated bioaerosols that do not correlate with the quality of the processed peat. Efficiency of dust removing systems could influence the contamination levels.

Air Pollutants, Occupational↗

Sensitization to airborne molds and its health effects in peat moss processing plant workers.

The goal of this study was to evaluate the incidence of sensitization to the major molds found in peat dust in workers exposed to stored peat moss and the health impact of this sensitization. Air samples from each plant were obtained to measure the levels of airborne molds, bacteria, and dust. There were 189 workers from 14 peat moss processing plants (3 all-year mixing plants and 11 seasonal plants) recruited for the study. The subjects completed a symptoms questionnaire, underwent spirometric measurements and skin-prick tests, and gave venous blood samples. Blood samples from 43 nonexposed control subjects were also taken. A similar percentage of smokers from both plant types was observed. Twenty-eight percent of the workers tested had a positive serum reaction to at least one of the tested molds. The percentage of positive workers varied from plant to plant, going from none in 4 plants to 14 out of 21 for 1 plant. This variability was not correlated with the airborne levels of molds. FEV tended to be lower in the workers with positive antibodies compared with seronegative workers. IgG positive frequency was higher for those workers employed in the all-year plants, and workers from those plants had lower FEV/FVC than seasonal plant workers. Seasonal plants were more contaminated with molds than all-year mixing plants, suggesting that the duration of exposure may trigger more sensitization than the level of exposure. We conclude that there is a high incidence of mold sensitization in peat moss factory workers and that this sensitization may have a negative respiratory health impact.

Adult↗

Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.

PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.

Aged↗

Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.

BACKGROUND: We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer. METHODS: We randomly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. RESULTS: A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). CONCLUSIONS: Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer.

Adult↗

Sex specificity of asthma associated with objectively measured body mass index and waist circumference: the Humboldt study.

STUDY OBJECTIVE: To investigate the possibility of sex specificity for the association of obesity and asthma using objective measures of body mass index (BMI) and waist circumference (WC). DESIGN: Cross-sectional study of adults (n = 2,057) living in Humboldt, SK, Canada in 2003. SETTING: A rural community. MEASUREMENTS: Ever-asthma was defined as lifetime physician-diagnosed asthma, and recent asthma was defined as asthma diagnosed by a physician during the past 12 months. BMI and WC were objectively measured. RESULTS: Among the participants, 5.6% of men and 10.0% of women reported having ever-asthma, and 2.7% and 6.0% had recent asthma, respectively. Higher levels of both BMI and WC were significantly associated with asthma in women but not in men. The adjusted odds ratios for women with a BMI of at least 30.0 kg/m2 relative to women with a BMI of < 25.0 kg/m2 were 2.06 (95% confidence interval [CI], 1.42 to 4.05) for ever-asthma and 3.47 (95% CI, 1.64 to 7.32) for recent asthma. CONCLUSIONS: Our study demonstrated that the increased risk of asthma associated with obesity was only significant in women but not in men even when BMI was objectively measured, and this association was robust to the anthropometric measures.

Adolescent↗

Pathogenesis of hypersensitivity pneumonitis.

PURPOSE OF REVIEW: Hypersensitivity pneumonitis is a group of immunologically mediated diseases caused by an abnormal response to a wide variety of inhaled antigens. Its pathogenesis is complex and involves many immunological concepts. This review discusses recent advances in our understanding of the pathogenesis of hypersensitivity pneumonitis. RECENT FINDINGS: Over the last 3 years, several studies on the pathogenesis of hypersensitivity pneumonitis have been published. New antigens have been identified. We now have a better understanding of the role of inflammatory cells and mediators, and promoting and protective factors have been suggested. SUMMARY: Most of the mechanisms involved in the pathogenesis of hypersensitivity pneumonitis remain incompletely understood. Current and future findings will not only help our understanding of the disease and its prevention, but also improve its treatment.

Alveolitis, Extrinsic Allergic↗

Chronic inflammation induced by organic dust and related metabolic cardiovascular disease risk factors.

OBJECTIVE: Chronic inflammation is now considered a risk factor for cardiovascular diseases. Exposure to organic dust induces an inflammatory response. This study was done to verify whether inflammation caused by exposure to organic dust increases the metabolic risk factors for cardiovascular diseases. METHODS: Thirty-six nonsmoking men who worked in a swine confinement building and 35 unexposed matched controls were studied. Each person was evaluated for inflammatory markers, including white blood cell counts, cell-bound (CD11b, CD18, CD31, CD62L) and circulating soluble adhesion molecule levels (sICAM-1, sPECAM-1, sL, sE, and sP selectins), serum CRP (C-reactive protein), fibrinogen, and interleukin-6 (IL-6). Cardiovascular risk factors [the serum lipid profile, apoprotein B (Apo B)] and insulin levels were also assessed. RESULTS: The groups were similar with respect to age, physical characteristics, and blood cell counts. The expression of adhesion molecules (P-values <0.01) and serum levels of sL-selectin (P<0.0001) were higher for the workers than for the controls, while neutrophils and interleukin-6 were slightly higher for the workers (P=0.05). No differences in CRP, fibrinogen, lipid profile, Apo B, or insulin levels were observed. CONCLUSIONS: Exposure to contaminated organic dust induces a chronic inflammation that is not associated with increased metabolic or acute-phase cardiovascular risk factors; this finding suggests that chronic inflammation per se may not be a cardiovascular risk factor in this group of pig farmers.

Adolescent↗

Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro.

The incidence of hypersensitivity pneumonitis (HP) is lower in smokers than in nonsmokers. Because nicotine is immunosuppressive, we hypothesized that it could have a protective effect on HP induction in vivo. HP was induced in mice that were treated with nicotine either intraperitoneally (IP) (0.5 to 2.0 mg/kg/day) or intranasally (IN) (0.025 to 2.0 mg/kg/day). Both IP- and IN-treated animals had fewer bronchoalveolar lavage total cells and lymphocytes and a decreased lung tissue inflammation. IFN-gamma but not interleukin-10 mRNA expression was reduced in lung tissue of 2.0-mg/kg IN-treated animals. To test the effect of nicotine on alveolar macrophages, AMJ2-C11 cells were treated with nicotine and stimulated with lipopolysaccharide or Saccharopolyspora rectivirgula, a causative agent of HP. Nicotine reduced tumor necrosis factor release and tumor necrosis factor, interleukin-10, and IFN-gamma mRNA expression after stimulation and decreased CD80 expression by 55% in lipopolysaccharide-stimulated cells and by 41% in S. rectivirgula-stimulated cells. We conclude that nicotine could be, at least in part, responsible for the protection observed in smokers against HP. The inhibitory effect of nicotine on alveolar macrophages could be one of the mechanisms involved.

Alveolitis, Extrinsic Allergic↗

Clinical diagnosis of hypersensitivity pneumonitis.

The diagnosis of hypersensitivity pneumonitis (HP) is difficult and often relies on histopathology. Our objective was to identify diagnostic criteria and to develop a clinical prediction rule for this disease. Consecutive patients presenting a condition for which HP was considered in the differential diagnosis underwent a program of simple standardized diagnostic procedures. High-resolution computed tomography scan and bronchoalveolar lavage (BAL) defined the presence or absence of HP. Patients underwent surgical lung biopsy when the computed tomography scan, BAL, and other diagnostic procedures failed to yield a diagnosis. A cohort of 400 patients (116 with HP, 284 control subjects) provided data for the rule derivation. Six significant predictors of HP were identified: (1) exposure to a known offending antigen, (2) positive precipitating antibodies to the offending antigen, (3) recurrent episodes of symptoms, (4) inspiratory crackles on physical examination, (5) symptoms occurring 4 to 8 hours after exposure, (6) and weight loss. The area under the receiver operating characteristic curve was 0.93 (95% confidence interval: 0.90-0.95). The rule retained its accuracy when validated in a separate cohort of 261 patients. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence, respectively, without BAL or biopsy.

Algorithms↗

The bone scan flare phenomenon in non-small-cell lung cancer.

PURPOSE: The bone scan flare phenomenon, defined as an increase in the number or intensity of bone lesions with subsequent improvement while the patient is receiving chemotherapy, has been described in solid tumors including breast cancers and small-cell lung cancers. The purpose of this study was to verify the existence of the bone scintigraphic flare phenomenon in patients with non-small-cell lung cancer (NSCLC) during chemotherapy and thus determine the utility of bone scintigraphy in the follow-up of these patients. MATERIALS AND METHODS: Thirty-three patients with NSCLC with bone metastases and who had been treated with chemotherapy were included in the study. The outcome of bone scintigraphy was compared with that in other neoplastic sites. RESULTS: The flare phenomenon was considered likely in 8 of the 33 patients. It was confirmed in two patients, invalidated in four, and remained doubtful in two. CONCLUSIONS: The bone flare phenomenon occurs in NSCLC. It renders bone scintigraphy less useful in the evaluation of tumoral response in the patients in whom it is considered likely.

Bone Neoplasms↗

Saccharopolyspora rectivirgula from Quebec dairy barns: application of simplified criteria for the identification of an agent responsible for farmer's lung disease.

Saccharopolyspora rectivirgula (Micropolyspora faeni) is one of the major agents responsible for farmer's lung disease, a form of hypersensitivity pneumonitis. It is frequently isolated from the air of contaminated barns. The identification of this actinomycete is difficult because most of its phenotypic characteristics are variable and classical tests are not easy to perform on actinomycetes. Fatty acid analysis is very useful for the identification of these strains, but is not available except in some research or reference laboratories. Morphological (microscopic and macroscopic observations), physiological and biochemical tests (growth properties; macromolecules degraded; citrate utilisation and acid production from carbohydrates; resistance to antibiotics, lysozyme and heat), cell wall and fatty acid analyses and IgG analyses with serum from patients with farmer's lung were performed on 12 environmental isolates presumed to be S. rectivirgula and two control strains of S. rectivirgula. From this, a simple and rapid scheme for the identification of this actinomycete is proposed: optimal growth temperature (55 degrees C); colony appearance based on morphology (filamentous) and colour (beige to orange-brown); microscopic morphology (chains of spores on both aerial and substrate mycelium); growth on NaCl 10%; cell-wall analysis (type IV); and the verification of antibody response with serum from a patient with farmer's lung. This last criterion is important to confirm the immunogenicity of the strains identified as S. rectivirgula. This scheme provides an accurate and efficient way of identifying S. rectivirgula strains and evaluating exposure to this bacterium. The study shows the limited value and the lack of reproducibility of some classical biochemical tests.

Actinomycetales Infections↗