M G Cosio

McGill University, Montréal, Quebec, Canada

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Publications (51)319.15 Total impact

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    ABSTRACT: To compare lung morphology in chronic obstructive pulmonary disease (COPD) secondary to cigarette smoke (CS) and biomass smoke (BS). Necropsies of women with COPD diagnosis by lung pathology and unique exposure to BS (n = 27) or CS (n = 21) matched by age and place of origin. Lungs were macroscopically and microscopically examined to evaluate the extent of emphysema, pigment deposition, and abnormalities in pulmonary arteries, large airways (including the Reid index) and small airways (SAWs) by a semiquantitative method. Both groups had variable degrees of emphysema and SAWs disease. Patients exposed to BS had more lung fibrosis and pigment deposition and thicker pulmonary arterial intima than smokers, who had more emphysema and epithelial damage (goblet cell metaplasia). The Reid index was similar in both groups. Lengthy exposure to BS can produce emphysema and other lesions typically observed in cigarette smokers, but with a slightly different distribution. Whether the differences observed are the consequence of severity of exposure or smoke composition, or both, remains to be clarified.
    The International Journal of Tuberculosis and Lung Disease 08/2008; 12(8):972-7. · 2.32 Impact Factor
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    M.G. Cosio
    European Respiratory Journal 08/2004; 24(1):3-5. DOI:10.1183/09031936.04.00043104 · 7.64 Impact Factor
  • Manuel G Cosio · Joaquim Majo · Monica G Cosio
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    ABSTRACT: A smoking-induced inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, has long been accepted to be the major cause of COPD in smokers. Recent reports have underlined the role of the T lymphocyte as a potentially important factor in the inflammatory process leading to COPD. It has been found that, in the airways and the lung parenchyma, the presence of T cells, predominantly CD8+ T cells, can distinguish between smokers with and without COPD. In addition to T cells, other inflammatory cell types such as neutrophils and macrophages are probably essential in the initial inflammatory process leading to the breakdown of lung tissue, perhaps producing peptides eventually recognized by T cells as antigenic. This would provide an explanation for the T-cell inflammation. Once activated, T cells are present in the lung, and their effector functions would include the attraction and enhancement of the inflammatory function in other inflammatory cells like neutrophils and macrophages. It seems likely that, only when all inflammatory cell types (ie, CD4+, CD8+, neutrophils, and macrophages) are present in the lung, the airways remodeling and parenchymal destruction characteristic of COPD will ensue. If T cells are responsible for the lung injury and progression of COPD, it would resemble a response to an antigenic stimulus originating in the lung. If that were the case, COPD could be considered to be an autoimmune disease triggered by smoking.
    Chest 06/2002; 121(5 Suppl):160S-165S. DOI:10.1378/chest.121.5_suppl.160S · 7.48 Impact Factor
  • M G Cosio Piqueras · M G Cosio
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    ABSTRACT: The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). The functional consequence of these abnormalities is airflow limitation. Airway abnormalities and emphysema interact in a complex fashion in the development of airflow limitation in COPD. In an attempt to improve understanding of the role of the airways in COPD, the morphological counterparts of airflow limitation, the cellular inflammatory infiltrate in the airways and the relationship between emphysema type and airway abnormalities are reviewed. Significant correlation between airway remodelling and functional measurements are found in earlier stages of COPD. In advanced COPD, airflow limitation is reflected by airway narrowing, airway deformity and extent of emphysema. The cellular inflammatory infiltrate is mainly composed of neutrophils in early stages of COPD. However, the presence of CD8+ T-cells seems to differentiate smokers with COPD from smokers that would not develop the disease. The inflammatory changes and remodelling found in the airways and their contribution to airflow obstruction might be modulated by the type of emphysema smokers develop, with centrilobular emphysema showing more severe inflammatory changes and narrower airways than panlobular emphysema. In conclusion, the degree of airway involvement in chronic obstructive pulmonary disease can vary greatly for the same degree of airflow obstruction, depending on the type of emphysema smokers develop. If the underlying lung abnormalities in chronic obstructive pulmonary disease vary, as the evidence suggests, the study of cigarette-induced lung disease as a single entity will further delay understanding of chronic obstructive pulmonary disease.
    The European respiratory journal. Supplement 01/2002; 34(1):41s-49s. DOI:10.1183/09031936.01.00234601
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    ABSTRACT: In 1996 we established a day hospital dedicated to acute respiratory care, as an alternative to emergency department and inpatient treatment. The unit is staffed by respirologists, family physicians and specialized nurses; patients have access to all standard inpatient treatments and services. Between 1996/97 and 1998/99 the annual number of admissions to the day hospital increased from 658 to 922. By 1998/99 more than 75% of patients were referred for acute treatment, with a mean stay of 2.3 days. The most common diagnoses were asthma and chronic obstructive pulmonary disease, which accounted for 58% and 32% respectively of treatment-related admissions. Treatment most often involved intravenous corticosteroid therapy and inhaled bronchodilator therapy. Between 1996/97 and 1998/9 the proportion of patients requiring transfer to overnight care decreased from 22% to 14%; complications and unscheduled return visits were rare. We believe that a respiratory day hospital provides a useful alternative to emergency department and inpatient care.
    Canadian Medical Association Journal 11/2001; 165(8):1067-71. · 5.96 Impact Factor
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    J Majo · H Ghezzo · M.G. Cosio
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    ABSTRACT: Previously, it had been shown that T-lymphocytes are the predominant inflammatory cells found in the alveolar wall of smokers and their numbers correlated with the extent of emphysema. However, the phenotype of these cells was not defined. The aim of this study was to describe the different T-cell phenotypes and investigate the possible presence of apoptosis in the lung parenchyma of smokers. Samples from lungs were obtained at surgery from 15 patients who smoked and six who had never smoked. Samples were frozen and prepared for histological and immunocytochemical examination. Slides were stained for CD3+, CD4+, CD8+, gammadelta T-cells, CD56 natural killers ((NK) cells), and elastase (neutrophils). Anti-CD95 monoclonal antibodies and in situ end-labelling techniques were used to detect Fas expression and apoptosis. Positive staining cells were expressed as cells-mm alveolar wall-, percentage of total cells, and Fas/APO and apoptosis index. Emphysema was identified macroscopically, microscopically and reported as present or absent. All subjects had pulmonary function tests before surgery. Neutrophils were the predominant cell in the lung parenchyma of nonsmokers and smokers without emphysema. In smokers with emphysema, the CD3+ and CD8+ were the predominant cells (p<0.05) in the alveolar wall. gammadelta cells were increased in all smokers and no increased numbers of NK cells was found. The T-cell numbers x mm alveolar wall(-1) showed a bilinear relationship with the amount smoked increasing at an inflection point of 30 packs yr(-1) (R2= 0.345; p < 0.01). Apoptosis in smokers showed a bilinear relationship with the amount smoked increasing sharply in smokers with emphysema (R2=0.3613; p < 0.009). It is concluded that the pathogenesis of emphysema might be mediated by T-lymphocytes, mainly CD8+ cytolytic T-cells, and that apoptosis might be one of the mechanisms of lung destruction leading to the development of emphysema. If this is the case, it could be speculated that T-cell inflammation is a response to antigenic stimuli originating in the lung and induced by cigarette smoking.
    European Respiratory Journal 06/2001; 17(5):946-53. DOI:10.1183/09031936.01.17509460 · 7.64 Impact Factor
  • M G Cosio · M G Cosio Piqueras
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    ABSTRACT: Emphysema is an almost constant finding in the lungs of chronic obstructive pulmonary disease patients. Several types of emphysema are recognized by pathologists, but only the centrilobular (CLE) and panlobular (PLE) emphysemas are found in association with smoking. In this review, the morphological and functional differences between CLE and PLE are described, and it is suggested that they could arise as different abnormalities as a result of the same insult, cigarette smoke. In CLE: 1) the destruction of the lung is uneven and originates around the airways; 2) the membranous bronchioles are thicker, narrower and more reactive than in PLE; 3) lung compliance is low or normal and does not relate to the extent of the emphysema; and 4) the decrease in flow is related mainly to the degree of airway abnormality and not to the losses of elastic recoil. In contrast, in PLE: 1) the destruction of the lung is even; 2) the small airways appear less narrowed and less inflammed than in CLE; 3) the compliance of the lung is increased and related to the extent of the emphysema; and 4) the decrease in flow is related mainly to the loss of elastic recoil and not to the abnormalities in the airways. The authors would propose that centrilobular emphysema and panlobular emphysema are distinct entities, centrilobular emphysema an airborne disease related to airway reactivity, panlobular emphysema a blood-borne disease related to abnormalities in lung protective mechanisms against inflammatory insults.
    Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 05/2000; 55(2):124-9.
  • M G Cosio · A Guerassimov
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    ABSTRACT: Currently available information suggests that cigarette smoke-induced lung inflammation has a pathogenic role in the development of COPD. Neutrophils, eosinophils, alveolar macrophages, and lymphocytes all appear to participate in the inflammatory process. However, the respective importance of these cells and their level of activation are difficult to quantitate because disease phenotyping, and compartmentalization of inflammation and markers of inflammation in the lung, influence the obtained data and bias their interpretation. Bronchoscopic biopsies are typically obtained from larger, cartilaginous airways containing submucosal glands whereas the site of airflow obstruction in COPD is predominantly the membranous bronchiole, devoid of cartilage and submucosal glands. This makes it difficult to establish structure-function relationships. The proportion of neutrophils has been reported to increase in repeated induced sputum and bronchoalveolar lavage samples. This observation suggests neutrophil recruitment into the airway is induced by the tests or sampling of different airway compartments in subsequent tests. There appears to be a good correlation between the proportions of eosinophils in induced sputum and bronchoalveolar lavage fluid on the one hand and in airway tissue on the other. However, this is not the case for other inflammatory cells, especially T lymphocytes, which are more numerous in airway tissue. Despite these inconsistencies, induced sputum, bronchoalveolar lavage, and bronchial biopsies can be used as markers of inflammation in COPD as long as their limitations are recognized. Cosio MG, Guerassimov A. Chronic obstructive pulmonary disease: inflammation of small airways and lung parenchyma.
    American Journal of Respiratory and Critical Care Medicine 12/1999; 160(5 Pt 2):S21-5. DOI:10.1164/ajrccm.160.supplement_1.7 · 13.00 Impact Factor
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    ABSTRACT: The negative expiratory pressure (NEP) method was used to detect expiratory flow limitation at rest and at different exercise levels in 4 normal subjects and 14 patients with chronic obstructive pulmonary disease (COPD). This method does not require performance of forced expirations, nor does it require use of body plethysmography. It consists in applying negative pressure (-5 cmH2O) at the mouth during early expiration and comparing the flow-volume curve of the ensuing expiration with that of the preceding control breath. Subjects in whom application of NEP does not elicit an increase in flow during part or all of the tidal expiration are considered flow limited. The four normal subjects were not flow limited up to 90% of maximal exercise power output (Wmax). Five COPD patients were flow limited at rest, 9 were flow limited at one-third Wmax, and 12 were flow limited at two-thirds Wmax. Whereas in all patients who were flow limited at rest the maximal O2 uptake was below the normal limits, this was not the case in most of the other patients. In conclusion, NEP provides a rapid and reliable method to detect expiratory flow limitation at rest and during exercise.
    Journal of Applied Physiology 04/1997; 82(3):723-31. · 3.06 Impact Factor
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    ABSTRACT: The aim of this study was to determine whether diaphragmatic fatigue develops over the course of the night in patients with obstructive sleep apnoea (OSA). Patients with severe OSA underwent overnight polysomnography with the addition of gastric and oesophageal catheters for measurement of transdiaphragmatic pressure (Pdi) (n = 7) and a gastro-oesophageal electrode for determination of diaphragmatic electromyogram (EMGdi) (n = 5). Analyses of Pdi and EMGdi were performed to detect fatigue during the large inspiratory efforts at the end of apnoeas in Stage 2 sleep at the beginning and end of the night. Measurements included Pdi values, shape analysis of the Pdi waveform, the relaxation rate (tau R) of Pdi, EMGdi and its relationship to Pdi, and the centroid frequency (fc) of EMGdi. End of apnoeic Pdi and EMGdi increased from the beginning to end of the night (e.g. 19 +/- 14% increase in Pdi; p < 0.05). The rate of increase in Pdi and EMGdi during apnoeas did not change. The Pdi versus EMGdi relationship was linear, and remained unchanged over the course of the night. There was no significant change in the shape of the Pdi waveform, and there were no changes in tau R from the beginning to the end of the night (0.13 +/- 0.01 s for both periods). There was also no shift in the fc of the EMGdi power spectrum (94 +/- 5 vs 93 +/- 6 Hz; NS), and no change in the relationship of fc to Pdi or EMGdi from the beginning to the end of the night. These findings do not support the development of diaphragmatic fatigue over the course of the night in obstructive sleep apnoea.
    European Respiratory Journal 01/1997; 10(1):133-8. DOI:10.1183/09031936.97.10010133 · 7.64 Impact Factor
  • S J Cala · P Sliwinski · M G Cosio · R J Kimoff
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    ABSTRACT: It has previously been reported that the duration of obstructive apneas increases from the beginning to the end of the night (M. Charbonneau, J. M. Marin, A. Olha, R. J. Kimoff, R. D. Levy, and M. Cosio. Chest 106: 1695-1701, 1994). The purpose of this study was to test the hypothesis that stimulation of upper airway (UA) sensory receptors during obstructed inspiratory efforts contributes to arousal and apnea termination and that a progressive attenuation of this mechanism through the night contributes to apnea lengthening. We studied seven patients (six men, one woman) with severe obstructive sleep apnea (apnea-hypopnea index = 93 +/- 26 events/h) during two consecutive nights of polysomnographic monitoring. On one night (random order), we performed topical UA anesthesia with 0.2% tetracaine and on the control night, sham anesthesia. We measured apnea duration, esophageal pressure (Pes) during apneas, and apneic O2 desaturation. Consistent with previous findings, apnea duration, number of efforts per apnea, and peak Pes at end apnea increased from the beginning to the end of the control nights. UA anesthesia produced a significant increase in apnea duration at the beginning of the night but no change in apnea length at the end of the night. Peak Pes and the rate of increase in Pes during the anesthesia nights were greater than during control nights, but the rate of increase in Pes was similar for the beginning and end of the control and anesthesia nights. These findings suggest that UA sensory receptors play a role in mediating apnea termination at the beginning of the night but that the contribution of these receptors diminishes as the night progresses such that greater inspiratory efforts are required to trigger arousal, leading to apnea prolongation.
    Journal of Applied Physiology 01/1997; 81(6):2618-26. · 3.06 Impact Factor
  • J M Montserrat · E N Kosmas · M G Cosio · R J Kimoff
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    ABSTRACT: We have previously shown in patients with obstructive sleep apnea (OSA) that the length of apneas increases from the beginning to the end of the night (Chest 1994;106:1695-1701). To investigate this, in light of recent evidence that neural feedback related to inspiratory effort during apneas plays an important role in apnea termination (Am. J. Respir. Crit. Care Med. 1994;149:707-714), we measured transdiaphragmatic pressure (Pdi) and the diaphragm tension-time index (TTdi = Pdi/Pdi(max)) Ti/Ttot) during overnight polysomnography in seven male subjects with severe OSA (mean apnea-hypopnea index [AHI] = 64.1 +/- 8.8 [SD] events/h). We assessed apnea duration, SaO2, and inspiratory effort during apneas at the start and end of the night in Stage 2 sleep. Mean apnea duration increased from 26.6 +/- 2.0 s (SEM) to 32.6 =/- 2.5 s (p < 0.05). The rate of fall in SaO2 during apneas decreased, and end-apneic SaO2 remained unchanged across the night, suggesting a possible role for metabolic factors in mediating the increase in apnea duration. Both Pdi and TTdi at end-apnea just prior to arousal increased significantly from the beginning to the end of the night (e.g., Pdi from 41.0 +/- 4.9 to 49.9 +/- 7.9 cm H20; p < 0.05). These findings, together with those in previous studies, suggest that there is a blunting over the night of the arousal response to neural stimuli produced during obstructed inspiratory effort, which plays a major role in mediating apnea lengthening across the night in OSA.
    American Journal of Respiratory and Critical Care Medicine 11/1996; 154(4 Pt 1):988-93. DOI:10.1164/ajrccm.154.4.8887596 · 13.00 Impact Factor
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    ABSTRACT: The purpose of this prospective study was to verify whether the percentage area of lung occupied by lowest attenuation values on high-resolution computed tomography (HRCT) scans reflects microscopic emphysema and to compare this quantification with the information yielded by the most widely used pulmonary function tests (PFT). Preoperative HRCT scans were obtained with 1-cm intervals in 38 subjects. With a semiautomatic evaluation procedure, the percentage areas occupied by attenuation values inferior to thresholds ranging from -900 Hounsfield units (HU) to -970 HU were calculated for the lobe or lung to be resected. Emphysema was microscopically quantified by using a computer-based method, measuring the perimeters and interwall distances of alveoli and alveolar ducts. The strongest correlation was found for -950 HU. As a second step, we evaluated possible correlations between PFT and microscopic measurements. Finally, considering the microscopic measurements as a standard, we tried to investigate their relationships with each of the PFT and with the relative area occupied by attenuation values lower than -950 HU for both lungs. This revealed that the diffusing capacity for carbon monoxide associated with HRCT quantification is sufficient to predict microscopic measurements. We concluded that the percentage area of lung occupied by attenuation values lower than -950 HU is a valid index of pulmonary emphysema.
    American Journal of Respiratory and Critical Care Medicine 08/1996; 154(1):187-92. DOI:10.1164/ajrccm.154.1.8680679 · 13.00 Impact Factor
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    ABSTRACT: External irradiation is an established palliative treatment for patients with inoperable lung cancer. However, persistent or recurrent symptoms due to local disase are common following external irradiation. The impact of high dose rate (HDR) brachytherapy in the palliative management of patients with local sequelae of residual or recurrent endobronchial lung carcinoma following external irradiation was investigated. A prospective cohort of 29 patients (19 men, mean age 65 years) underwent HDR brachytherapy for inoperable lung cancer. All patients had completed external irradiation at least one month before entry into the study (mean (SD) dose 4400 (1481) cGy, completed 12.9 (21.3) months previously). Patients underwent outpatient bronchoscopic placement of 1-3 HDR brachytherapy catheters for delivery of 750-1000 cGy of intraluminal irradiation every two weeks on 1-3 occasions. Prospective evaluation before and four weeks after completion of HDR brachytherapy included assessment of indices of level of function, symptoms, extent of atelectasis (chest radiography), and bronchoscopic determination of degree of endobronchial obstruction. One hundred and eighteen catheters were placed in 81 treatments. Eleven of the 26 patients who underwent repeat bronchoscopy showed a reduction in the degree of endobronchial obstruction; five of 18 patients had radiographic improvement in the extent of atelectasis. Positive response rates ranged from 25% for signs and symptoms related to pneumonitis to 69% for haemoptysis. Performance status improved in 24% of patients. Two patients died before completion of the study protocol. Short term complications included one episode of non-fatal, massive haemoptysis, five of minor haemoptysis, and one pneumothorax. HDR brachytherapy may improve the degree of endobronchial obstruction, atelectasis, symptoms, and level of function with minimal short term complications in patients with recurrent or residual symptomatic disease following external irradiation.
    Thorax 05/1996; 51(4):354-8. DOI:10.1136/thx.51.4.354 · 8.29 Impact Factor
  • M G Cosio · J Majó
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    ABSTRACT: In summary, emphysema in smokers should not be considered a single entity with predictable clinical and functional abnormalities. Decreases in flow are the ultimate abnormalities seen in COPD with emphysema; however, the pathophysiology of the flow alterations are vastly different in CLE and PLE. Based on the present understanding of emphysema, it could be predicted that the short-term results of pneumonectomy might produce some improvement in flows in CLE but not in PLE. Any improvement, however, may be short-lived, because the new mechanical conditions resulting from the removal of emphysematous lung would destroy the remaining lung at an accelerated rate, thus returning to the prior emphysematous state.
    Chest Surgery Clinics of North America 12/1995; 5(4):603-21.
  • R Finkelstein · R S Fraser · H Ghezzo · M G Cosio
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    ABSTRACT: The prevalent theory in the pathogenesis of emphysema proposes that increased numbers of activated neutrophils and/or alveolar macrophages produce large amounts of proteases, an activity that cannot be regulated by alpha 1-antiproteases, resulting in lung destruction. However, the cells in the lung parenchyma of smokers have not been properly identified. We characterized and quantitated the inflammatory cell load in the lungs of smokers and correlated these findings with the degree of lung destruction. Twenty-one patients, six nonsmokers and 15 smokers, undergoing lung resection were studied. Lungs or lobes were fixed and stained for light microscopy and neutrophil identification and immunohistochemically stained for identification of lymphocytes and macrophages. By point counting, we determined the extent of emphysema by the volume density of the lung parenchyma (Vvalv), and the different cell numbers per cubic millimeter in all lungs. In nonsmokers Vvalv was greater than in smokers. The number of neutrophils/mm3 of lung correlated directly with the Vvalv, (r = 0.71, p < 0.01), whereas the number of alveolar macrophages (r = -0.70) and T-lymphocytes (r = -0.78) correlated negatively with the Vvalv. The number of T-lymphocytes correlated negatively with the number of neutrophils (r = -0.58) and positively with the numbers of alveolar macrophages (r = 0.77). Our data suggest that as long as the inflammatory reaction is predominantly of neutrophils there is no destruction of the lung. However, the extent of lung destruction becomes evident, and its extent is directly related to the number of alveolar macrophages and T-lymphocytes/mm3. We conclude that the T-lymphocyte might be importantly implicated in the pathogenesis of emphysema in smokers.
    American Journal of Respiratory and Critical Care Medicine 11/1995; 152(5 Pt 1):1666-72. DOI:10.1164/ajrccm.152.5.7582312 · 13.00 Impact Factor
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    ABSTRACT: Nitric oxide (NO) has been detected in the expiratory air of normal animals and human subjects. Recent experiments revealed that expiratory NO production rises during exercise and correlates well with O2 consumption (VO2) and heart rate. Whether physical conditioning influences expiratory NO output production remains unclear. In this study, NO concentration in expired gas was measured in 18 healthy male volunteers subdivided into three groups (sedentary, intermediate, and athletic) on the basis of the subjects' state of physical conditioning. Measurements were taken at rest and during two steady-state exercise bouts on a bicycle ergometer designed to elicit VO2 of 1 and 2 l/min with the athletes performing an additional bout at VO2 of 4 l/min. In the sedentary and intermediate groups, expired NO concentrations declined significantly with increasing VO2. In contrast, expired NO levels declined only slightly with increasing VO2 in the athletes. At a VO2 of 2 l/min, expired NO concentrations were significantly higher in the athletes compared with values in the other groups. When correlated with minute ventilation (VE), expired NO concentrations declined linearly with the increase in VE in sedentary and intermediate groups but not in the athletes. Only the athletes had a significant linear increase in NO output (expired NO x VE) with increasing VO2 (P < 0.001). These results support the notion that physical conditioning increases expiratory NO output during exercise. We speculate that the rise in expiratory NO output in the athletes might be due to increased vascular and/or epithelial production of NO. Enhanced vascular NO production may be the result of increased shear stress and/or upregulation of endothelial NO synthase gene expression.
    Journal of Applied Physiology 10/1995; 79(4):1219-25. · 3.06 Impact Factor
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    ABSTRACT: Based on our previous finding, of increased small airways disease in centrilobular emphysema (CLE) when compared with panlobular emphysema (PLE), we hypothesized that smokers who develop CLE would have increased airway responsiveness associated with airway inflammation and exaggerated airway narrowing, but not smokers with PLE. We compared preoperative methacholine challenge with the morphologic and cellular inflammatory characteristics of the airways in the lungs of six nonsmokers, 10 smokers with CLE, and five smokers with PLE. The airways of the CLE group were narrower than those of the nonsmokers (KS < 0.05) and the PLE group (KS < 0.05), but perimeters were not different. A greater percentage of airways in the CLE group showed infolding of the epithelium and lumen deformity than in the PLE group and nonsmokers (p < 0.05). Airway inner wall thickening (WI) was increased in the CLE group when compared with the PLE group and nonsmokers (p < 0.05), and WI correlated significantly with PC20 in the CLE group (r = -0.64, p < 0.01) but not in the PLE group and nonsmokers. The number of T lymphocytes in the airway walls correlated with PC20 in the CLE group (r = -0.50, p < 0.05) but not in the PLE group. In conclusion, despite similar age, smoking history, and range of airflow limitation, there was a clear difference in the methacholine responsiveness between the emphysema groups, suggesting that responsiveness is not just a reaction to smoking but either a reaction developing in some smokers or an abnormality initially present in some smokers which, in combination with exposure to cigarettes, determines the development of a type of lung disease: CLE.
    American Journal of Respiratory and Critical Care Medicine 08/1995; 152(1):267-76. DOI:10.1164/ajrccm.152.1.7599834 · 13.00 Impact Factor
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    M Charbonneau · J M Marin · A Olha · R J Kimoff · R D Levy · M G Cosio
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    ABSTRACT: It was our impression that the respiratory parameters in obstructive sleep apnea (OSA) worsened as the night progressed. To confirm this, we review polysomnographic studies from 66 patients with apnea-hypopnea indices (AHI) of 40 to 125 events per hour, dividing bed time into equal quartiles. As the night progressed, the mean apnea duration (MAD) increased from 27.2 s to 34.6 s (p < 0.0001), mainly from increases during NREM sleep. The proportion of time spent in apnea increased from 54 to 71% (p < 0.0001) due to increases in both MAD and the proportion of REM sleep (from 2.8 to 14.7% of the total sleep time). The AHI did not change significantly between quartiles. Even though preapneic oxygen saturation did not change and apnea duration increased as the night progressed, the end-apneic saturation did not decrease, hence the rate of oxygen desaturation decreased. Also, it was found that patients with an AHI greater than 65 events per hour increased their proportion of time spent in apnea significantly more than those with an AHI smaller than 65, as the night progressed. In the patients with an AHI greater than 85, this was due to both an increase in MAD and AHI. In conclusion, in patients with an AHI greater than 40 events per hour, the severity of apnea increased as the night progressed due to lengthening of MAD, increased proportion of REM sleep, and in the most severe patients, also an increase in AHI. Even though the exact pathophysiologic mechanisms for the observed changes are unknown, a decrease in respiratory muscle effort with consequent decrease in oxygen consumption may explain both the lengthening of the apneas and the decrease in the rate of oxygen desaturation.
    Chest 12/1994; 106(6):1695-701. DOI:10.1378/chest.106.6.1695 · 7.48 Impact Factor
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    M Saetta · R Finkelstein · M.G. Cosio
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    ABSTRACT: Airflow limitation has two well-defined components, increased resistance, which is found predominantly in the small airways, and loss of elastic recoil. Small airways contribute to the increased resistance to flow by the narrowing of the airway lumen. Morphometric studies have shown that smokers have increased epithelial abnormalities, cellular inflammatory infiltrates in the airway wall, increased muscle and fibrosis, when compared with nonsmokers. Along with these anatomical changes, an increased percentage of airways < 400 microns in diameter is found. In addition to the measured changes, other nonmeasurable, dynamic events occur in the airways of smokers, which further decrease lumen diameter. There is ample evidence to show that the airways of smokers react to nonspecific stimuli by constricting, which results in increased resistance and decreased forced expiratory volume in one second (FEV1). The pathological changes found in smokers, that could be responsible for active muscle constriction and airway narrowing include: 1) airway epithelial damage, resulting in increased permeability and impairment of other epithelial function; 2) chronic airway inflammation; 3) structural changes in the airway wall; and 4) loss of alveolar attachments. However, not all smokers develop the abovementioned airway abnormalities. We describe how smokers could develop either centrilobular emphysema (CLE), or panlobular emphysema (PLE). We have found that smokers with CLE have more abnormal and narrower small airways, and flow limitation is correlated with the small airway abnormalities and not with loss of recoil. In contrast, smokers with PLE have much less severe airway abnormalities, diffuse emphysema that can be detected microscopically at a stage when FEV1 might be only mildly abnormal, and early changes in elastic recoil as evidenced by the changes in the pressure-volume curve of the lung. Furthermore, in PLE, airflow limitation is correlated with loss of recoil but not with abnormalities in the small airways. We believe that the mechanisms involved in the pathogenesis of the two types of emphysema in smokers are different; an airborne mechanism for CLE, possibly related to airway hyperresponsiveness, and a bloodborne mechanism for PLE, which may be related to dysfunction of alpha 1-antiproteases. We conclude that the separation of smokers based on their emphysema type is essential if we are to understand the pathogenesis of chronic obstructive pulmonary disease (COPD) in these subjects.
    European Respiratory Journal 08/1994; 7(8):1505-15. DOI:10.1183/09031936.94.07081505 · 7.64 Impact Factor

Publication Stats

2k Citations
319.15 Total Impact Points


  • 1984–2008
    • McGill University
      • • Respiratory Division
      • • Meakins-Christie Laboratories
      • • Department of Medicine
      Montréal, Quebec, Canada
  • 1991
    • Hôpital du Sacré-Coeur de Montréal
      Montréal, Quebec, Canada