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C G Irvin

Publications and source records attributed to C G Irvin.

At least 19 recordsLinked to original sources
PubMed1999

Bradykinin-induced bronchospasm in the rat in vivo: a role for nitric oxide modulation.

Bradykinin has an important role in asthma pathogenesis, but its site of action is unclear. It was previously reported by the authors that bradykinin causes a dose-dependent reduction in dynamic compliance but little change in total lung resistance. This suggested that bradykinin may have a preferential effect in the distant lung. The purpose of the current investigation was to better characterize the effects of bradykinin on pulmonary resistance in rodents and explore the role of nitric oxide release in modulating the effect of bradykinin. Airway constriction was induced in the rats by aerosol administration of bradykinin with or without treatments with the inhaled bradykinin-2 receptor antagonist, Hoe 140 or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester or N(G)-monomethyl-L-arginine. Total lung resistance was partitioned into tissue and airway resistance by using the alveolar capsule method. Bradykinin induced a significant increase in both resistances. Hoe 140 abolished the response to bradykinin. The nitric oxide synthase inhibitors enhanced the bronchoconstricting response. In conclusion, the bradykinin response in the rats was not only localized to conducting airways but also involved a relatively selective tissue reaction. Bradykinin-induced bronchospasm in the rat is solely due to activation of bradykinin-2 receptor. Further, it was shown that nitric oxide significantly modulates the bronchospasm caused by bradykinin, suggesting that nitric oxide is an important modulator of airways responsiveness to bradykinin.

Airway Resistance↗
PubMed1997

Development of eosinophilic airway inflammation and airway hyperresponsiveness in mast cell-deficient mice.

Mast cells are the main effector cells of immediate hypersensitivity and anaphylaxis. Their role in the development of allergen-induced airway hyperresponsiveness (AHR) is controversial and based on indirect evidence. To address these issues, mast cell-deficient mice (W/W v) and their congenic littermates were sensitized to ovalbumin (OVA) by intraperitoneal injection and subsequently challenged with OVA via the airways. Comparison of OVA-specific immunoglobulin E (IgE) levels in the serum and numbers of eosinophils in bronchoalveolar lavage fluid or lung digests showed no differences between the two groups of mice. Further, measurements of airway resistance and dynamic compliance at baseline and after inhalation of methacholine were similar. These data indicate that mast cells or IgE-mast cell activation is not required for the development of eosinophilic inflammation and AHR in mice sensitized to allergen via the intraperitoneal route and challenged via the airways.

Airway Resistance↗
PubMed1997

5-Lipoxygenase products are necessary for ovalbumin-induced airway responsiveness in mice.

To determine the role of 5-lipoxygenase products in the development of airway reactivity that follows antigen exposure, we sensitized mice by intraperitoneal injection of ovalbumin and aluminum hydroxide and serial exposure to aerosols of ovalbumin. Mice lacking a functioning 5-lipoxygenase enzyme were produced by targeted gene disruption. They and their wild-type controls had measurements of lung resistance (RL) made in response to intravenous methacholine; bronchoalveolar lavage fluid cell counts and serum immunoglobulin concentrations were also measured. Wild-type mice developed striking increases in cholinergic responsiveness; 5-lipoxygenase-deficient mice manifested minimal alterations in methacholine responsiveness (RL at the highest methacholine dose was 9.9 +/- 2.4 cmH2O.ml-1.s-1 under control conditions vs. 27.6 +/- 4.6 cmH2O.ml-1.s-1 after ovalbumin in wild-type mice; 5.9 +/- 0.9 vs. 7.01 +/- 2.2 cmH2O.ml-1.s-1 in 5-lipoxygenase-deficient mice). Ovalbumin provoked airway eosinophilia and increased immunoglobulins in wild-type mice, which were present to a significantly lesser degree in 5-lipoxygenase-deficient mice. We conclude that 5-lipoxygenase products are essential for the production of nonspecific airway reactivity in mice and suggest that 5-lipoxygenase products may be important in immunoglobulin formation.

Aerosols↗
PubMed1997

Hyperpnea-induced changes in parenchymal lung mechanics in normal subjects and in asthmatics.

The effects of hyperpnea on parenchymal lung mechanics are unknown, but they may contribute to the resultant airflow limitation commonly seen in asthma. To investigate these effects, we measured the following parameters in seven asthmatic and six normal subjects before and after 5 min of hyperpnea: specific conductance, upstream resistance, static compliance, the coefficient of retraction, lung volumes, lung hysteresis, and the ratio of maximal to partial flow rates (the M:P ratio, an indicator of the effect of deep inhalation on airflow, and a measure of relative airway and parenchymal hysteresis). In addition to a central effect on the airways, as shown by significant falls in specific conductance, hyperpnea in asthmatics, but not in normal subjects, resulted in significant increases in residual volume and pressure-volume hysteresis, suggestive of changes in parenchymal lung mechanics. The M:P ratio also increased in the asthmatics, consistent with greater increases in airway than in parenchymal hysteresis after hyperpnea. We conclude that hyperpnea has significant effects on the lung parenchyma that contribute to airflow limitation in asthmatics, and we hypothesize that these effects may be due to alterations in peripheral airway smooth muscle tone and surfactant function.

Adult↗
PubMed1997

Quality control of peak flow meters for multicenter clinical trials. The Asthma Clinical Research Network (ACRN).

Although peak expiratory flow (PEF) measurements are recommended for monitoring and assessing treatment of asthmatic patients, and widely employed to assess outcome in clinical trials and epidemiologic studies, information about performance of peak flow meters (PFM) under field conditions is lacking. We describe a simple testing system consisting of a testing chamber, a spirometer, and a calibration syringe to evaluate the relative accuracy or median relative bias (MRB), precision, or inter-quartile range (IQR) of the mini-Wright PFM. The relative accuracy ranged from -4.4 to 13.2% (mean, 4.1%) and the precision from 0.06 to 11.5% (mean, 1.2%). Durability of this PFM was assessed during a 26-wk clinical trial in 255 asthmatic subjects at five centers. Seventy-one PFM (19.9%) were identified as having failed to meet acceptance criteria, predominantly because of loss of relative accuracy, by the clinics at follow-up visits (n = 36), and by the Data Coordinating Center on retrospective review of quality control measurements submitted by the clinics (n = 35). This study indicates that a simple device can be used to evaluate the relative accuracy and precision of a given PFM and to ensure the quality of PEF measurements during a clinical trial. To the extent that one can extrapolate these data to other devices, our findings indicate that the failure rate of PFM over time can be high, indicating that quality control of a PFM over time is absolutely essential in clinical trials as well as in routine clinical care.

Asthma↗
PubMed1997

Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography.

To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric whole-body plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive technique also demonstrated increased pulmonary resistance responses to aerosolized methacholine when measured using an invasive technique the following day in the same animals. The increases in Penh values were inhibited by pretreatment of the mice with a beta 2-agonist. These data indicate that measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice. The measurement of AR in unrestrained, conscious animals provides new opportunities to evaluate the mechanisms and kinetics underlying the development and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.

Airway Resistance↗
PubMed1997

Methacholine challenge testing: safety of low starting FEV1. Asthma Clinical Research Network (ACRN).

STUDY OBJECTIVE: The lower limit for the baseline value to initiate methacholine bronchial hyperresponsiveness testing has not been well established. Recommendations have varied from > 1 L to above 80% of predicted. The objective was to determine if an FEV1 < 60% predicted was acceptable. DESIGN: Retrospective analysis of challenges in 88 patients with a baseline FEV1 of < 60% predicted (mean=45.8%; range, 22 to 59%. SETTING: Academic institutions. RESULTS: There were only four individuals whose FEV1 did not return to > 90% of baseline following one poststudy beta2-agonist treatment. All four responded to a second treatment. There were no adverse sequelae following challenge in any individual. Neither age (up to 79 years) nor gender influenced outcome. CONCLUSIONS: In chronic moderate to severe asthma, it appears that bronchial hyperresponsiveness testing can be safely performed even in those patients with a low baseline FEV1.

Adrenergic beta-Agonists↗
PubMed1997

Office spirometry: equipment selection and training of staff in the private practice setting.

Spirometry is a basic pulmonary function test that is widely used for the detection of airflow limitation. Its use will continue to grow in the medical office setting because it is useful for both diagnostic and monitoring purposes. Additionally, the assessment of airflow reversibility is a quick, safe, and useful adjunct to baseline spirometry. Many manufacturers offer various models and types of spirometers. Before purchasing, determine the needs and characteristics of the office and its staff, and then choose an appropriate device. There is no "holy grail" for selecting what instrument is best for a specific office. Rather, it requires time and effort to make a good choice. Carefully assess the instrument before purchase and, ideally, compare several instruments. Once an instrument is purchased and it arrives, carefully validate it before reporting results. Proper training of the technicians who perform the testing is perhaps the most important factor in obtaining good spirometric testing. After adequate training, it is also important to have continued competency assessments, periodic inservices, and careful review of test results. The ATS and American Association for Respiratory Care (AARC) published extensive guidelines on the performance of spirometry. These recommendations should be followed to ensure quality and reduce interlaboratory variability. Patients should be properly prepared, the instrumentation properly calibrated, and the test conducted so that there is a good start, adequate exhalation time, satisfactory end-of-test, and good reproducibility between trials.

Age Factors↗
PubMed1996

Pulmonary histiocytosis X: pulmonary function and exercise pathophysiology.

Pulmonary histiocytosis X (PHX) is a diffuse, smoking-related lung disease characterized pathologically by bronchocentric inflammation, cyst formation, and widespread vascular abnormalities and physiologically by exercise limitation. The major mechanism underlying exercise impairment in this disease has not been previously defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on 23 patients with PHX. Two subgroups were identified on the basis of elastic recoil: 12 subjects had an elevated coefficient of elastic recoil with 11 demonstrating a predominant pattern of restriction, and 10 subjects had normal elastic recoil and relatively normal lung function. Exercise performance was severely limited in both subgroups (workload 53 +/- 3%). Abnormalities of ventilatory function and gas exchange were present but did not appear to be exercise-limiting in the majority of subjects. Indices reflecting pulmonary vascular function (DLCO, baseline VD/VT, exercise VD/VT) were abnormal. Strong correlations between overall exercise performance (% predicted VO2max) and indices of vascular involvement were present: DLCO (r = 0.68, p = 0.0004), baseline VD/VT (-0.65, 0.001), exercise VD/VT (-0.67, 0.0004). Similar correlations were found when exercise performance was measured by maximal workload achieved. We conclude that (1) subjects with PHX present with either normal or predominantly restrictive pulmonary physiology and that (2) exercise impairment is common and appears to reflect pulmonary vascular dysfunction.

Adult↗
PubMed1996

Lymphangioleiomyomatosis: the pathophysiology of diminished exercise capacity.

Dyspnea with exertion is nearly always present in patients with pulmonary lymphangioleiomyomatosis, but the mechanisms underlying exercise impairment have not been well defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on a cohort of 16 patients. We determined the relative contribution of airflow limitation, gas exchange abnormalities, and pulmonary vascular abnormalities to the exercise performance achieved. The patients had normal TLC and Vtg, but RV was elevated in 88% of the subjects. A moderate to severe obstructive pattern was present in 69% of the subjects, and the DLCO was reduced, often markedly, in 81% of the subjects. Exercise performance was limited (work load, 68% +/- 6) with abnormalities of ventilatory function and gas exchange present. Strong correlations between overall exercise performance (percent predicted VO2max and maximal work load achieved) and indices of airflow and vascular involvement were present. Poor exercise performance was due primarily to ventilatory limitation. The etiology of this ventilatory limitation appears twofold. First, subjects had a reduced ventilatory ceiling because of airflow limitation. Second, subjects demonstrated an excessive ventilatory response as a result of increased dead-space ventilation thought to be due to disease-associated cystic changes and associated pulmonary vascular dysfunction or destruction.

Adult↗
PubMed1996

Quantitative CT predicts the severity of physiologic dysfunction in patients with lymphangioleiomyomatosis.

PURPOSE: To assess quantitative high-resolution CT (quantitative CT) as a diagnostic and prognostic tool in pulmonary lymphangioleiomyomatosis. METHODS: Spirometry, lung volumes, diffusing capacity, exercise physiology, and expiratory high-resolution CT (HRCT) examinations were performed on a cohort of ten patients with the diagnosis of lymphangioleiomyomatosis (LAM) referred to a tertiary care center. HRCT examinations were also done on ten normal control subjects. A thresholding technique was used to quantitatively assess the amount of abnormal cystic parenchyma present on each of the two images obtained for each subject with LAM and for each normal control subject. This numeric index of cystic parenchyma, the quantitative CT index, was then examined (1) as a diagnostic measure to distinguish the subjects with LAM from the normal control subjects and (2) as a prognostic measure to assess disease severity in the subjects with LAM. Linear regression of the quantitative CT index against physiologic indexes of pulmonary function and exercise performance was analyzed to determine the relationship between this radiologic assessment of disease severity and functional impairment. RESULTS: The quantitative CT index was significantly greater for the LAM patients, 37.2 +/- 6.9 (SEM), compared with the control group, 0.8 +/- 0.2 (p = 0.0001). Linear regression analysis demonstrated significant linear correlation between the quantitative CT index and measures of airflow (FEV1, r = -0.90, p = 0.0005), air trapping (residual volume, r = 0.70, p = 0.02), diffusing capacity (diffusing capacity for carbon monoxide, r = -0.76, p = 0.01), gas exchange (alveolar to arterial oxygen gradient) at rest, r = 0.69, p = 0.007, and at maximum exercise, r = 0.79, p = 0.007) and exercise performance (maximum workload, r = -0.84, p = 0.002), and oxygen utilization (oxygen utilization at maximum exercise, r = -0.76, p = 0.01). CONCLUSION: Quantitative CT techniques can distinguish subjects with LAM from normal controls. Further, the quantitative CT index correlates well with physiologic measurements of airflow, lung volumes, diffusing capacity, and exercise performance and, thus, may provide a useful measure of disease severity.

Adult↗
PubMed1995

Quantitative chest computed tomography as a means of predicting exercise performance in severe emphysema.

RATIONALE AND OBJECTIVES: We assessed the value of quantitative high-resolution computed tomography (CT) as a diagnostic and prognostic tool in smoking-related emphysema. METHODS: We performed an inception cohort study of 14 patients referred with emphysema. The diagnosis of emphysema was based on a compatible history, physical examination, chest radiograph, CT scan of the lung, and pulmonary physiologic evaluation. RESULTS: As a group, those who underwent exercise testing were hyperinflated (percentage predicted total lung capacity +/- standard error of the mean = 133 +/- 9%), and there was evidence of air trapping (percentage predicted respiratory volume = 318 +/- 31%) and airflow limitation (forced expiratory volume in 1 sec [FEV1] = 40 +/- 7%). The exercise performance of the group was severely limited (maximum achievable workload = 43 +/- 6%) and was characterized by prominent ventilatory, gas exchange, and pulmonary vascular abnormalities. The quantitative CT index was markedly elevated in all patients (76 +/- 9; n = 14; normal < 4). There were correlations between this quantitative CT index and measures of airflow limitation (FEV1 r2 = .34, p = 09; FEV1/forced vital capacity r2 = .46, p = .04) and between maximum workload achieved (r2 = .93, p = .0001) and maximum oxygen utilization (r2 = .83, p = .0007). CONCLUSION: Quantitative chest CT assessment of disease severity is correlated with the degree of airflow limitation and exercise impairment in pulmonary emphysema.

Aged↗
PubMed1995

Peripheral airways responsiveness to cool, dry air in normal and asthmatic individuals.

Peripheral airways resistance (Rp) has been shown to be increased in asymptomatic asthmatic patients with normal spirometric values, and to be correlated with airways hyperresponsiveness to methacholine. We investigated whether Rp in asthmatic subjects with exercise-induced bronchospasm (EIB) would rise in response to cool, dry air. Using a wedged bronchoscope technique, we challenged an isolated lung segment with high flows (500 to 1,000 ml/min) of cool (22 degrees C) dry 5% CO2 in air for 5 min in eight asthmatic subjects with EIB and eight normal subjects. Baseline Rp and Rp following challenge were measured with saturated air at 37 degrees C at a flow rate of 100 ml/min. Baseline Rp was significantly greater in the asthmatic (0.09; [0.05 to 0.23] cm H2O/ml/min; median [interquartile range]) than in the normal subjects (0.05; [0.03 to 0.07] cm H2O/ml/min) (p = 0.04). The asthmatic, but not the normal subjects, had a significant absolute maximal increase in Rp following cool, dry air (0.10 [0.03 to 0.15] cm H2O/ml/min) (p < 0.01). In the asthmatic subjects, baseline Rp correlated with airways hyperresponsiveness to exercise (r = -0.76, p = 0.03). We conclude that the peripheral airways of asthmatic individuals with EIB are responsive to cool, dry air, and may play an important role in EIB.

Airway Resistance↗
PubMed1995

Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation.

In the current series of experiments we investigated the role of bradykinin in airway hyperresponsiveness induced by human eosinophil-granule major basic protein (MBP). Bronchoalveolar lavage was performed after intratracheal instillation of MBP or poly-L-lysine in anesthetized, intubated rats, and levels of immunoreactive kinins and kallikrein-like activity were determined. Both MBP and poly-L-lysine induced a three- and eightfold increase in levels of kallikrein-like activity and i-kinins, respectively. To determine whether kinin production is required for the development of airway hyperresponsiveness induced by cationic proteins, dose-response curves to methacholine were constructed before and 1 h after intratracheal instillation of either MBP or poly-L-lysine (100 micrograms). MBP and poly-L-lysine induced an increase in airway responsiveness, which was inhibited by pretreatment with a selective BK-2 receptor antagonist, NPC 17713 (250 micrograms/ml). Our results demonstrate that MBP and poly-L-lysine activate kallikrein and stimulate the generation of i-kinins in vivo, an effect that may be related to the cationic charge of these proteins. Furthermore, the ability of these proteins to increase airway responsiveness appears to be dependent on the generation of i-kinins.

Amino Acid Sequence↗
PubMed1995

Methacholine challenge does not affect bronchoalveolar fluid cell number and many indices of cell function in asthma.

Methacholine (MCh) challenge testing is often incorporated into clinical studies prior to performing bronchoscopy as a measure of bronchial hyperresponsiveness (BHR). However, the effect of methacholine on many aspects of bronchoalveolar lavage (BAL) fluid cell count and function have not been fully evaluated. Ten patients with asthma, maintained on inhaled beta 2-agonists, were studied. Each subject underwent two bronchoscopies in a random order, one preceded by methacholine challenge within 30 min of the BAL. The investigators were blinded to the regimen. Several markers of BAL fluid cell number and function were studied: cell count and differential histamine, eosinophil products, including eosinophil cationic protein and Charcot-Leyden crystal protein, macrophage production of thromboxane B2 and leukotriene B4, neutrophil lysozyme and lactoferrin, and lymphocyte typing and activation markers measured via flow cytometry. No significant differences were noted in any of these markers of cell number or function which could be ascribed to methacholine challenge. Thus, methacholine challenge does not appear to affect these markers of cell number and function. These findings indicate that a methacholine challenge can be used as a measure of bronchial hyperresponsiveness within 30 min prior to bronchoscopy without altering bronchoalveolar lavage fluid characteristics.

Adult↗