PubMed Health⌕ Search

Biomedical subjects

Peter D Paré

Publications and source records attributed to Peter D Paré.

36 records · Page 2Linked to original sources
PubMed2004

Physiological changes at altitude in nonasthmatic and asthmatic subjects.

Exercised-induced asthma is not due to exercise itself per se, but rather is due to cooling and/or drying of the airway because of the increased ventilation that accompanies exercise. Travel to high altitudes is accompanied by increased ventilation of cool, often dry, air, irrespective of the level of exertion, and by itself, this could represent an 'exercise' challenge for asthmatic subjects. Exercise-induced bronchoconstriction was measured at sea level and at various altitudes during a two-week trek through the Himalayas in a group of nonasthmatic and asthmatic subjects. The results of this study showed that in mild asthmatics, there was a significant reduction in peak expiratory flow at very high altitudes. Contrary to the authors' hypothesis, there was not a significant additional decrease in peak expiratory flow after exercise in the asthmatic subjects at high altitude. However, there was a significant fall in arterial oxygen saturation postexercise in the asthmatic subjects, a change that was not seen in the nonasthmatic subjects. These data suggest that asthmatic subjects develop bronchoconstriction when they go to very high altitudes, possibly via the same mechanism that causes exercise-induced asthma.

Adolescent↗
PubMed2004

Reconcilable differences: a cross-sectional study of the relationship between socioeconomic status and the magnitude of short-acting beta-agonist use in asthma.

STUDY OBJECTIVE: To assess the association between socioeconomic status (SES) and short-acting (SA) beta-agonist use, controlling for asthma severity. DESIGN: Cross-sectional study. SETTING: Vancouver, BC, Canada. PARTICIPANTS: Two hundred two asthmatics between 19 years and 50 years of age and residing in the greater Vancouver regional district. MEASUREMENTS: The quantity of SA beta-agonist used in the previous year was collected by self-report; pulmonary function and beta-receptor genotype were measured on each participant. SES was measured at both the individual and population levels. Five methods of adjustment for asthma severity were used, as follows: the Canadian Asthma Consensus Guidelines, three previously developed asthma-severity scores, and forward stepwise multiple regression modeling. Polychotomous logistic regression was used to assess all relationships. RESULTS: Independent of the method used to measure SES or adjust for asthma severity, lower SES was consistently and significantly associated with the use of greater amounts of SA beta-agonist. Adjusting for severity using the multivariate model explained the most variance of SA beta-agonist use (R(2) adjusted, 0.35 to 0.37). In this model, social assistance recipients were more likely to use greater amounts of SA beta-agonist (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.7 to 6.5). An inverse relationship between SA beta-agonist use and both annual household income (> $50,000; OR, 0.28; 95% CI, 0.13 to 0.60; and $20,000 to $50,000; OR, 0.44; 95% CI, 0.21 to 0.96; relative to <$20,000) and education (completing a bachelor's degree vs no formal education; OR, 0.25; 95% CI, 0.14 to 0.71). Participants living in a neighborhood with higher median household income (OR, 0.91; 95% CI, 0.84 to 0.98 per $1,000 increase) or a higher prevalence of having attained a bachelor's degree (OR, 0.96; 95% CI, 0.84 to 0.98 per 1% increase) were also less likely use greater amounts of SA beta-agonist. Results were consistent for neighborhood unemployment rate. CONCLUSIONS: The social gradient in asthma-related outcomes may be at least partially attributable to poorer asthma control in lower-SES asthmatics.

Adrenergic beta-Agonists↗
PubMed2003

Deep inspiration and airway smooth muscle adaptation to length change.

In normal subjects a deep inspiration (DI) taken during bronchoconstriction substantially reduces airway narrowing (bronchodilation) and a DI taken prior to bronchoconstriction attenuates subsequent airway narrowing (bronchoprotection). Although the exact mechanism(s) for these phenomena are unclear the time course of these effects supports the hypothesis that they are mediated through actions of airway smooth muscle (ASM). There is convincing evidence that both the bronchodilation and bronchoprotection actions of DI are deficient or absent in asthmatic subjects. Various theories have been proposed such as a failure of transmission of stress and strain to the ASM in asthma, stretch-induced contraction of smooth muscle in asthmatics, a failure to release bronchodilating substances and differential effects on cross-bridge dynamics or contractile element rearrangement. In this brief review we focus on the mechanical consequences of DI on the ASM. We suggest that a failure of plastic rearrangement of the contractile apparatus following DI is at the basis of the abnormal response to DI in asthma.

Adaptation, Physiological↗
PubMed2003

Structure-function correlation in airway smooth muscle adapted to different lengths.

Airway smooth muscle is able to adapt and maintain a nearly constant maximal force generation over a large length range. This implies that a fixed filament lattice such as that found in striated muscle may not exist in this tissue and that plastic remodeling of its contractile and cytoskeletal filaments may be involved in the process of length adaptation that optimizes contractile filament overlap. Here, we show that isometric force produced by airway smooth muscle is independent of muscle length over a twofold length change; cell cross-sectional area was inversely proportional to cell length, implying that the cell volume was conserved at different lengths; shortening velocity and myosin filament density varied similarly to length change: increased by 69.4% +/- 5.7 (SE) and 76.0% +/- 9.8, respectively, for a 100% increase in cell length. Muscle power output, ATPase rate, and myosin filament density also have the same dependence on muscle cell length: increased by 35.4% +/- 6.7, 34.6% +/- 3.4, and 35.6% +/- 10.6, respectively, for a 50% increase in cell length. The data can be explained by a model in which additional contractile units containing myosin filaments are formed and placed in series with existing contractile units when the muscle is adapted at a longer length.

Adaptation, Physiological↗
PubMed2003

Characterization of airway plugging in fatal asthma.

PURPOSE: Case reports suggest that deaths due to asthma can occur without airway plugging. In this study, we examined the hypothesis that obstruction of the airway lumen by an exudate containing mucus and cells is a key feature of fatal asthma attacks. METHODS: We quantified airway narrowing and lumenal content in 275 airways from 93 patients with fatal asthma aged 10 to 49 years (59 white subjects and 34 Polynesian subjects, including 19 children), compared with airways from control patients who died suddenly without pulmonary diseases. RESULTS: The severity of lumenal occlusion ranged from 4% to 100% in these cases, but only five airways showed less than 20% occlusion. Compared with controls, patients with asthma had more lumenal occlusion (mean [+/- SD] open lumen, 42% +/- 23% vs. 93% +/- 8%), greater mucus occlusion (28% +/- 13% vs. 5% +/- 6%), and more occlusion by cells (30% +/- 17% vs. 3% +/- 2%, all P<0.0001). Airway narrowing was greater in larger airways (P<0.0001) and older patients (P = 0.009). Greater lumen content was associated with a higher proportion of cells (P = 0.003), and cells made up a higher proportion of the exudate in the small airways (P<0.0001). Lumenal mucus was greater in younger patients with asthma (P = 0.0007) and in Polynesian patients with asthma (P = 0.04). CONCLUSION: Airway lumenal obstruction by an exudate composed of mucus and cells is a major contributing cause of fatal asthma in most patients.

Adolescent↗
PubMed2003

Role of exercise and nutrition status on bone mineral density in cystic fibrosis.

BACKGROUND: Exercise has been shown to maintain or increase bone mineral density (BMD) in non-CF populations. OBJECTIVES: The purpose of our study was to elucidate the relationship between exercise, body composition and dietary intake with BMD in an adult CF population with heterogeneous disease severity. DESIGN: We measured spinal (L1-4) and femoral (femoral neck) BMD by dual energy X-ray absorptiometry (DEXA) in 68 CF adults (24 female, 44 male) with a mean age 30.8(1.7) and 27.4(1.3) (range 18-55) years. We used the average BMD Z score for spine and femoral neck for analyses. Differences in disease severity, exercise capacity, physical activity level, dietary intake, body composition, body mass index (BMI), glucocorticoid use were correlated with BMD scores. Exercise capacity was defined as the maximal amount of oxygen consumed by muscles during maximal exercise (Vo2max). Vertebral and non-vertebral fracture rate were also recorded. RESULTS: Fifty-seven patients were identified with low BMD (Z score < -1). Multiple linear regression identified exercise capacity and BMI as significant predictors of BMD. Later diagnosis of CF was also associated with low adult BMD. CONCLUSIONS: Low BMD is common in adult CF patients. Exercise capacity and BMI are predictors of low BMD.

Absorptiometry, Photon↗
PubMed2002

Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers.

Oxidative stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease. We hypothesized that polymorphisms of antioxidant genes glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, and heme oxygenase-1 (HMOX1) would be associated with susceptibility to accelerated decline of lung function in smokers. We genotyped 621 subjects (299 rapid decliners [change in forced expiratory volume in 1 second (DeltaFEV(1)) = -152 +/- 2.5 ml/year] and 322 nondecliners [DeltaFEV(1) = +15 +/- 1.5 ml/year]) selected from among smokers followed for 5 years in the National Heart, Lung, and Blood Institute Lung Health Study. Because genotype frequencies were different between ethnic groups, we limited the association study to 594 whites (286 rapid decliners and 308 nondecliners). None of the genotypes studied had a statistically significant effect on decline of lung function when analyzed separately. There was an association between rapid decline of lung function and presence of all three GST polymorphisms (odds ratio [OR] = 2.83; p = 0.03). A combination of a family history of chronic obstructive pulmonary disease with GSTP1 105Ile/Ile genotype was also associated with rapid decline of lung function (OR = 2.20; p = 0.01). However, due to the multiple comparisons that were made, these associations may represent type 1 error. There was no association between HMOX1 (GT)n alleles and the rate of decline in lung function in smokers.

Adult↗
PubMed2002

The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function.

The matrix metalloproteinases (MMPs) comprise a family of at least 20 proteolytic enzymes that play an essential role in tissue remodeling. MMP1 (interstitial collagenase), MMP9 (gelatinase B) and MMP12 (macrophage elastase) are thought to be important in the development of emphysema. A number of naturally occurring polymorphisms of human MMP gene promoters have been identified and found to alter transcriptional activity. Additionally, we detected a novel polymorphism in the MMP12 coding region (Asn357Ser). The aim of this study was to investigate the role of MMP polymorphisms in the development of chronic obstructive lung disease. We determined the prevalence of these polymorphisms in 590 continuing smokers chosen from the National Heart Lung and Blood Institute, Lung Health Study for having the fastest (n = 284) and slowest (n = 306) 5 year rate of decline of lung function. Of the five polymorphisms, only G-1607GG was associated with a rate of decline in lung function. The -1607GG allele was associated with a fast rate of decline (P = 0.02) [corrected]. However, haplotypes consisting of alleles from the MMP1 G-1607GG and MMP12 Asn357Ser polymorphisms were associated with rate of decline of lung function (P = 0.0007). These data suggest that polymorphisms in the MMP1 and MMP12 genes, but not MMP9, are either causative factors in smoking-related lung injury or are in linkage disequilibrium with causative polymorphisms.

Base Sequence↗
PubMed2002

Genetic risk factors of chronic obstructive pulmonary disease.

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only a minority of cigarette smokers develop symptomatic disease. Family and twin studies suggest that genetic factors also contribute to the development of COPD. We present a detailed literature review of the genes which have been investigated as potential risk factors for this disease.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed2002

Genetic risk factors for chronic obstructive pulmonary disease.

Cigarette smoking is clearly the major risk factor for chronic obstructive pulmonary disease. However, only a minority of cigarette smokers develops chronic obstructive pulmonary disease, indicating that other factors are involved. Family and twin studies suggest that at least some of those factors are genetic. This article reviews the genes investigated as potential risk factors for this disease, focusing on the recent literature. The only established genetic risk factor for chronic obstructive pulmonary disease is homozygosity for the Z allele of the alpha1 -antitrypsin gene. There is increasing evidence that heterozygotes for the Z allele may also be at increased risk. Variants in genes involved in xenobiotic metabolism, antioxidation, and the inflammatory response have also been associated with chronic obstructive pulmonary disease. Thus, the genetic basis for chronic obstructive pulmonary disease has begun to be elucidated, and it is likely that several genes will be implicated in the pathogenesis of this disease.

Alleles↗
PubMed2002

Tissue elastance influences airway smooth muscle shortening: comparison of mechanical properties among different species.

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus approximately 60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only approximately 12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (approximately 22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to approximately 9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.

Animals↗
PubMed2002

Zero-stress state of intra- and extraparenchymal airways from human, pig, rabbit, and sheep lung.

Alterations in airway wall anatomic properties and the consequential effects on airway narrowing have been assessed by use of computational models. In these models, it is generally assumed that at zero transmural pressure the airway wall exists in a zero-stress state. Many studies have shown that this is often not the case, as evidenced by a nonzero opening angle. In this study, we measured the opening angle of airway rings at zero transmural pressure to test this assumption. The airway tree was dissected from human, pig, sheep, and rabbit lungs. Airways were excised from the tree, and the opening angle was measured. There were obvious species and regional differences in opening angle. Rabbit airways from both extraparenchymal and intraparenchymal sites exhibited marked opening angles (7-82 degrees). Extraparenchymal airways from sheep had large opening angles (up to 50 degrees), but ovine intraparenchymal airways had small opening angles. Measurable opening angles were rarely observed in human and porcine airways of any size. The assumption of a stable zero-stress state at zero transmural pressure is therefore valid for human and porcine, but not rabbit and sheep, airways.

Adolescent↗
PubMed2002

Changes in force-velocity properties of trachealis due to oscillatory strains.

The physically dynamic environment of the lung constantly modulates the mechanical properties of airway smooth muscle. In vitro experiments have shown that contractility of the muscle is compromised by oscillatory strains, perhaps through disruption of cross-bridge interaction and organization of the contractile filaments. To understand the mechanism by which oscillation affects contractility, functional changes of the muscle in terms of force-velocity relationship were assessed before and after imposition of length oscillation in both relaxed and activated states. The oscillation protocol was designed to reduce isometric force by 15-20%, followed by measurement of force-velocity properties. Maximal velocity and power changed by +8 and -14%, respectively, after oscillation applied in the relaxed state and changed by -15 and -25%, respectively, after oscillation applied during contraction. A simple model of reduced activation could not account for the results; neither could the results be explained satisfactorily by the current cross-bridge theory of contraction. The results, however, could be explained if the possibility of reorganization of the contractile filaments due to oscillatory strains was considered.

Animals↗
PubMed2002

Patterns of inhaled asthma medication use: a 3-year longitudinal analysis of prescription claims data from British Columbia, Canada.

STUDY OBJECTIVES: To assess trends in asthma management and to identify factors associated with increasing short-acting (SA) beta-agonist utilization in British Columbia using administrative prescription data. DESIGN: A retrospective cohort analysis. SETTING: All patients between 13 and 50 years of age who had received at least one prescription for a SA beta-agonist covered by BC Pharmacare between January 1, 1996, and December 31, 1998. METHODS: Cross-sectional analysis of all patients, and longitudinal analyses only of patients who had received at least one SA beta-agonist prescription in each of the 3 years. Trends in asthma medication use over time were evaluated using repeated-measures Mantel-Haenszel tests. Multiple logistic regression was used to identify factors associated with increasing SA beta-agonist use. RESULTS: A total of 78,758 patients were included in the cohort. No decrease in the annual prevalence of receiving more than four canisters per year of a SA beta-agonist was identified between 1996 and 1998. A total of 12,844 patients filled at least one SA beta-agonist prescription each year. Time-trend analysis showed an overall increasing probability of not receiving an inhaled corticosteroid (ICS) agent in this population (p = 0.002). In patients exhibiting low SA beta-agonist use, > 18 years of age (adjusted odds ratio [OR], 1.5), male gender (adjusted OR, 1.7), and in receipt of social assistance (adjusted OR, 2.3) were associated with receiving increasing amounts of SA beta-agonist agents over the 3 years. In patients with a high degree of use of SA beta-agonists, only the receipt of social assistance (adjusted OR, 1.3) was significantly associated with increasing use. CONCLUSIONS: Despite the development and dissemination of asthma management guidelines, there was no trend toward decreasing SA beta-agonist use. An unexpected trend toward decreasing ICS utilization was identified. Receiving social assistance was a risk factor for increasing SA beta-agonist use, independent of baseline utilization.

Administration, Inhalation↗
PubMed2002

Quantitative assessment of airway remodeling using high-resolution CT.

Asthma and COPD are the most prevalent of lung diseases and contribute an enormous burden of morbidity in North America and globally. In both conditions, inflammation leads to airway remodeling, which contributes to airway narrowing. To date, airway remodeling has only been assessed using histological examination of airways. However, it may now be possible to assess and quantify the extent of airway remodeling in vivo using high-resolution CT (HRCT). The aim of this article is to review the use of HRCT in the investigation of airway remodeling. A number of investigators have reported techniques to make measurements of airway dimensions using CT and an increasing number of quantitative methods are being developed. Using these techniques, airway dimensions have been examined in patients with asthma and COPD. In patients with asthma, the airway wall area was increased without a decrease in luminal area, whereas in patients with COPD, the airway luminal area was decreased and airway wall area was increased. The different pattern of remodeling may reflect fundamental differences in the inflammatory processes in asthma and COPD and could influence the reversibility of the narrowing. It has also been shown that, by quantifying both the extent of emphysema and of airway remodeling, CT is useful in differentiating COPD patients who have primarily parenchymal disease from those who have primarily airway pathology. With additional advances in technology, it is likely that quantitative assessment of airway wall dimensions will ultimately provide a valuable tool for the study of airway disease.

Airway Obstruction↗