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Biomedical subjects

H Ghezzo

Publications and source records attributed to H Ghezzo.

At least 109 records · Page 6Linked to original sources

Destructive index: a measurement of lung parenchymal destruction in smokers.

Destruction of alveolar walls is considered by most observers to be the most important part in the definition of emphysema, yet it has never been precisely defined and quantitated. We therefore attempted to devise a reliable microscopic technique to quantitate alveolar destruction that would be both sensitive to disease and easy to perform. Using a point-count system, we obtained an index of parenchymal destruction that represents the percentage of destroyed space as a fraction of the total alveolar and duct space. We have called this measurement the destructive index (DI). In the lungs of 8 nonsmokers and 23 smokers, we quantitated the DI and compared it with the mean linear intercept (Lm) and with pulmonary function in smokers. Although Lm was not significantly different in the 2 groups, significant differences between the DI of smokers and nonsmokers (p less than 0.005) were found. In addition, the DI correlated with FEV1(-0.43, p less than 0.05), MMEF (r = -0.44, p less than 0.05), and recoil pressure at 90% TLC (r = -0.61, p less than 0.05) in smokers. These findings suggest that the destructive component of emphysema can be easily quantitated microscopically, occurs in smokers before dimensional changes are evident (i.e., increased Lm), and influences lung function. Therefore, the quantitation of this destruction (DI) could add greatly to the microscopic definition of emphysema, complementing the information given by the dimensional component of emphysema (Lm).

Aged↗

Kinetics of the recovery of airway response caused by inhaled histamine.

The time course of recovery from airway response induced by the inhalation of progressively doubling doses of histamine phosphate (3 to 4 depending on the subject) was studied in 8 asthmatic subjects by serial measurements of lung resistance (RL). For every subject, the time required for functional recovery became longer with increasing histamine doses and/or degrees of airway response. The slopes of the curves obtained from a single exponential fit relating time on the abscissa and functional recovery on the ordinate were significantly (F = 4.9 to 50.0, p less than 0.01) and progressively lower in 7 of 8 instances. This suggested a multiple compartment model, which was confirmed (r2 greater than or equal to 0.95) in 5 subjects by applying a double exponential regression that provided the most satisfactory fit. We conclude that the recovery from airway response caused by inhaled histamine is longer with increasing doses of histamine and/or degrees of airway response. A double-compartment model, a fast one followed by a slow one, fit this pattern of recovery in 5 of the 8 subjects.

Adult↗

Loss of alveolar attachments in smokers. A morphometric correlate of lung function impairment.

We studied post-mortem 9 nonsmokers' lungs and 9 smokers' lungs as well as 14 surgical smokers' lungs to examine the possible relationship of the number of alveolar attachments with airways inflammation and with lung function. Alveolar attachments are the alveolar walls radially attached to the small airways, and any discontinuity or rupture of these alveolar walls was considered abnormal. Normal and abnormal attachments were counted in nonsmokers and smokers and expressed as number of attachments, distance between attachments, and percentage of abnormal attachments. Although internal small airways diameter and mean linear intercept were not significantly different between smokers of either group and nonsmokers, significant differences in number of attachments (p less than 0.001), distance between attachments (p less than 0.01), and percentage of abnormal attachments (p less than 0.01) were found. The 3 indexes of alveolar attachments correlated significantly with the score for airways inflammation and with the elastic recoil pressure in smokers. No significant correlation with any other lung function test was found. We conclude that smokers have fewer alveolar attachments than do nonsmokers, and that the loss of alveolar attachments represents an early stage in the destruction of lung parenchyma, and is probably linked to inflammation of the small airways. Because of the strategic situation of this lesion, it could be responsible in part for the loss of elastic recoil seen in the initial stages of chronic obstructive pulmonary disease.

Aged↗

Effect of sodium cromoglycate on histamine inhalation tests.

Sixteen adult asthmatic subjects in a clinical steady state were included in the study. On day 1, after baseline assessment of spirometry (FEV1, FEV1/FVC, FEF25-75), they underwent three to four consecutive inhalation tests using twofold increasing doses of histamine to measure the provocative concentration causing a fall in FEV1 of 20% (PC20). Baseline FEV1 was back to +/- 5% of the initial assessment before each histamine inhalation test (HIT). On days 2, 3, and 4, after baseline spirometry which confirmed that FEV1 was within 10% of initial day 1 assessment, placebo-lactose (P) or 40 mg of sodium cromoglycate (SCG) were nebulized in a double-blind randomized 4.3.1. two-treatment crossover study design. Ten minutes later, spirometry was repeated and followed by an HIT. Baseline spirometry was not significantly different on each day or after P and SCG. There was no statistical difference between the geometric means of the three or four PC20's done on day 1, indicating that there is no tachyphylaxis induced by repeated HIT. There was no statistical difference between mean PC20 after P (0.52 +/- 3.3 (SD) mg/ml), after SCG (0.50 +/- 3.2), and of the three to four HIT done on day 1 (0.40 +/- 3.6). We conclude that in asthmatic subjects SCG has no acute bronchodilator effect and does not alter the response to inhaled histamine.

Adult↗

Histamine phosphate has a cumulative effect when inhaled at five minute intervals.

As the duration of bronchoconstriction induced by inhaled histamine phosphate is greater than five minutes, a study was carried out to determine whether this leads to a cumulative effect when histamine is inhaled at five minute intervals as in standardised procedures. Fourteen clinically stable adult asthmatic subjects were studied. In the first part of the study (the noncumulative stage) they inhaled doubling concentrations of histamine until appreciable bronchoconstriction occurred (changes close to 50% in lung resistance for seven subjects and 15% in forced expiratory volume in one second for seven others). After functional recovery the last concentration of histamine was nebulised on two more occasions, allowing for functional recovery after each nebulisation. In the second part of the study (the cumulative stage) subjects inhaled, depending on their responsiveness, three to eight consecutive doses of the histamine concentration last administered in the non-cumulative stage, these doses being administered at five minute intervals, without recovery. The cumulative effect was assessed by linear regression analysis of the changes in the specific functional indices, all the values obtained during the non-cumulative stage being given the score 0 and those obtained during the cumulative step scores of 1, 2, etc. In all but one instance significant (p less than 0.01) correlations were obtained and the slopes were positive, thus showing a cumulative effect. It is concluded that histamine has a cumulative bronchoconstrictor effect if inhaled at five minute intervals once appreciable bronchoconstriction has been reached.

Adult↗

Combined therapy with ipratropium and theophylline in asthma.

Ipratropium (40 micrograms) and theophylline (oxtriphylline 400 mg) were administered to 24 asthmatics in a randomized double-blind placebo controlled trial. The combination of these agents produced additive bronchodilation for up to two hours, with a 23 percent maximal increase in FEV1. This regimen promises to be safe, effective therapy for patients with asthma.

Adolescent↗

Respiratory pressures and function in young adults.

The relationships of lung functions to maximal respiratory pressure relative to the role of other recognized determinants (height, weight, age, and smoking status) were examined in 924 healthy Caucasian urban residents, 369 males 15 to 35 yr of age and 555 females 13 to 35 yr of age. In subjects no longer thought to be growing in stature, height was the main determinant of most functions. After height, respiratory pressures were the main determinant of forced vital capacity (FVC), forced expiratory volume in one second (FEV), and peak flow in men and women, with weight also an important determinant in women. Age had no consistent effect, and, although functions in smokers were lower than in nonsmokers for several tests, the effects were only significant for FEV and forced expiratory flow during the middle half of the FVC in women. These findings indicate that, if required, between-subject variation in this age group can be reduced by taking into account the relatively simple measurement of maximal inspiratory and expiratory pressures.

Adolescent↗

Relationship between the single-breath N test and age, sex, and smoking habit in three North American cities.

This report describes a collaborative study conducted in Montreal, Canada, Portland, Ore., and Winnipeg, Canada, to establish the relationship between the single-breath N2 test and age, sex, and smoking and to determine the prevalence of functional abnormalities in these populations. In nonsmokers, age-related regressions for closing volume, closing capacity, and the slope of phase III obtained from the single-breath N2 test, plus the ratio of the I-s forced expiratory volume to the forced vital capacity had very similar slopes, suggesting that differences in geographic location, climate, air pollution, and occupation had no effect on lung function detectable by these tests. Among the 6 city/six groups there was no systematic difference in the prevalence of functional abnormalities between the cities, but closing capacity expressed as a percentage of total lung capacity was abnormal most often in men and the slope of the alveolar plateau was abnormal most often in women. The prevalence of respiratory symptoms within different smoking categories was similar in the 3 cities. Although the number of cigarettes smoked had a significant effect on every test except the ratio of the I-s forced expiratory volume to forced vital capacity in men, the effect of age was considerably greater than the effect of smoking, and the dose-response relationship was weak. We conclude that additional factors may interact with smoking to place a smoker at risk of developing chronic airflow limitation.

Adult↗

The relations between structural changes in small airways and pulmonary-function tests.

To examine the relation between small-airways abnormalities and specific lung functions, we performed pulmonary-function tests in 36 patients, of whom two were nonsmokers, one to three days before open-lung biopsy for localized pulmonary lesions. The primary lesion in the small airways was a progressive inflammatory reaction leading to fibrosis with connective-tissue deposition in the airway walls. Increase in disease in small airways correlated with deterioration in lung function. Lesions could be reliably detected (P less than 0.05) by tests for closing capacity, the volume at which air and helium flow ere equal (a test of airway caliber and elastic recoil), and the slope of phase III of the single-breath washout curve (which tests evenness of ventilation). These tests showed abnormalities at a time when the pathologic changes were still potentially reversible and when other tests were not appreciably changed.

Adult↗

Age and sex differences in lung elasticity, and in closing capacity in nonsmokers.

Static volume-pressure characteristics of the human lung, closing capacity (CC), closing pressure, and subdivisions of lung volumes were measured in 66 adult nonsmokers, aged 24-58 yr. There were systemic differences between the sexes as well as with age. Young females had less elastic recoil at any lung volume than young males. However, males lost elastic recoil with age faster than females so that in the older age groups the recoil was similar. There were no significant changes in compliance over the volume range containing most values of CC in either males or females. By comparing the age regression of CC and of elastic recoil pressures at 40 and 50% TLC we conclude that the increase in CC with age in males was attributable almost entirely to loss of recoil. In females none of the increase in closing capacity with age was attributable to loss of recoil. By exclusion, it is probably attributable to a change in the intrinsic properties of small airways or an increase in the pleural pressure gradient with age.

Adult↗

Paper stamp checklist tool enhances asthma guidelines knowledge and implementation by primary care physicians.

BACKGROUND: The Canadian Clinical Practice Guidelines (CPGs) for the management of asthmatic patients were last published in 1999, with updates in 2001 and June 2004. Large disparities exist in the implementation of these guidelines into clinical practice. OBJECTIVE: The present study evaluated the knowledge of Quebec-based primary care physicians regarding the CPGs, as well as patient outcomes before and after introducing physicians to a new clinical tool--a memory aid in the form of a self-inking paper stamp checklist summarizing CPG criteria and guidelines for assessing asthmatic patient control and therapy. The primary objective of the present study was to assess whether the stamp would improve physicians' knowledge of the CPGs, and as a secondary objective, to assess whether it would decrease patient emergency room visits and hospitalizations. METHODS: A prospective, randomized, controlled study of 104 primary care physicians located in four Quebec regions was conducted. Each physician initially responded to questions on their knowledge of the CPGs, and was then randomly assigned to one of four groups that received information about the CPGs while implementing an intervention (the stamp tool) aimed at supporting their decision-making process at the point of care. Six months later, the physicians were retested, and patient outcomes for approximately one year were obtained from the Régie de l'assurance maladie du Québec. RESULTS: The stamp significantly improved physicians' knowledge of the CPGs in all Quebec regions tested, and reduced emergency room visits and hospitalizations in patients who were followed for at least one year. CONCLUSION: A paper stamp summarizing CPGs for asthma can be used effectively to increase the knowledge of physicians and to positively affect patient outcomes.

Asthma↗

Maximal static respiratory pressures in adults: normal values and their relationship to determinants of respiratory function.

Assessment of respiratory muscle strength is done most directly by measuring maximal static inspiratory and expiratory mouth pressures (MIPS and MEPS, respectively). The available studies that report reference values of MIPS and MEPS, however, show ill-explained wide variability, not only between individuals but also between studies. This study of 106 normal white adults (60 women and 46 males, aged 16 to 79 yr) attempts to identify the anthropometric factors which best predict MIPS and MEPS. It was found that: 1) smoking does not affect MIPS and MEPS; 2) sex is a major determinant of MIPS and MEPS, as women reached 68 and 63%, respectively, of the male values; 3) within each sex, age is the major determinant of MIPS and MEPS, since body size factors such as height, weight and percent ideal body weight do not significantly improve the relationship between age and MIPS or MEPS. In both sexes, the pattern of change in pressures with age is different for MIPS and MEPS, suggesting different maturation processes for MIPS and MEPS. While MIPS is an inverse linear function of age (i.e. MIPS decreases with advancing age from early adulthood on), the relationship between MEPS and age is best described by a second degree polynomial (i.e. MEPS increases towards a peak in mid-life, after which it also decreases with age).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Bronchoconstriction due to isocapnic cold air inhalation minimally influences bronchial hyperresponsiveness to methacholine in asthmatic subjects.

The aim of this study was to investigate if bronchial hyperresponsiveness to methacholine could be influenced by a previous bronchoconstriction due to isocapnic inhalation of cold air. Twelve adult asthmatic subjects in a clinical steady state were seen on four different days in a randomized way according to three different sequences. After assessment of spirometry, bronchial responsiveness to inhaled methacholine was determined on each occasion by the provocative concentration causing a fall of 20% in FEV1 (PC20). On two occasions, the methacholine test was preceded by the inhalation of dry cold air which caused significant (greater than 20% change in FEV1) bronchoconstriction. The methacholine test was performed after functional recovery. There was a significant (t = 2.53; p less than 0.05) but minimal (mean changes of 0.65 single two-fold concentration difference) reduction in PC20 after cold air inhalation. It is concluded that cold air-induced bronchoconstriction causes significant but minimal changes in bronchial responsiveness to methacholine in asthmatic subjects.

Asthma↗

Pulmonary function tests and airway responsiveness to methacholine in chronic bronchiectasis of the adult.

Fifty adults with chronic bronchiectasis (mean duration since diagnosis: 25 +/- 16.4 years), excluding those cases secondary to tuberculosis or hypogammaglobulinemia, were investigated by a questionnaire, a chest radiograph and lung function tests. Of these, 29 with an FEV1 greater than 1.5 1 underwent methacholine inhalation tests. Fourty-three subjects and three subjects respectively showed an obstructive or a mixed obstructive and restrictive defect, only four having normal lung function tests. Sixty-nine percent of subjects tested had a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) less than 16 mg X ml-1. Subjects with daily sputum production had lower values of FEV1 and FEV1/forced vital capacity (FVC) compared to subjects with less than daily sputum. Subjects with clinical features of bronchial hyperexcitability had significantly lower baseline FEV1, vital capacity, and maximal mid-expiratory flow rate (FEF25-75). Subjects with lower PC20 values had significantly lower baseline FEV1, FEV1/FVC and FEF25-75. Finally, subjects with the greatest extent of radiological abnormalities had lower baseline FEV1, FEV1/FVC and diffusing capacity, and a higher residual volume. We conclude that chronic bronchiectasis is associated with significant changes in lung function tests and increased responsiveness to methacholine in the majority of affected individuals.

Adult↗

Circadian variations of airway response to histamine in asthmatic subjects.

In 15 clinically stable asthmatic subjects, histamine inhalation challenges were carried out on six different days, at 8, 16 and 22 h, twice at each time. On each visit, baseline functional measurements including FEV1 and forced mid-expiratory flow rates (FEF25-75%) were followed by the assessment of the concentration of histamine causing a 20% fall in FEV1 (PC20). There was no significant difference in baseline lung function tests and PC20 for visits done either at the same or different times. The correlation coefficients of PC20 for the visits at 8, 16 and 22 h were 0.95, 0.88 and 0.78 respectively. The dispersion of results of PC20 was significantly (p less than 0.05) more pronounced at 22 h than at 8 h. The cosinor analysis which depicts biologic rhythms as sinusoidal curves [8] revealed that seven subjects had detectable diurnal rhythms with acrophases (time of least excitability) at 9.8, 10.0, 11.8, 15.3, 15.4, 22.2 and 23.1 h. In five and three of these seven subjects respectively, significant rhythms of FEV1 and FEF25-75% were also detected with similar acrophases.

Adult↗

Lung function changes as a reflection of tissue aging in young adults.

We studied 198 healthy young men and women 17 to 40 years of age, 110 blacks and 88 whites, all current non-smokers, with a view to identifying the changes, if any, consistent with lung tissue aging. Measurements were made of the maximal expiratory flow-volume (MEFV) curves (from which were derived forced vital capacity (FVC) and flow rates (Vmax) at 75%, 50% and 25% of expired VC), and transfer factor for carbon monoxide (TL). To describe aging trends, results were corrected for height differences and analysed by sex and race for five age groups. Certain changes (e.g. the age-related increase in FVC in men in the early 20's and decrease in the late 20's in both men and women) may be accounted for by changes in respiratory muscle force and/or increasing weight; in addition, the changes in FVC itself (used as the reference lung volume for reading flow rates off the MEFV curves) may have accounted in part for the age-related changes in Vmax at 75% and 50% VC. Likewise, increasing weight by influencing lung emptying may have contributed to the decrease in the diffusion constant in women. Only the age-related decline in Vmax at 25% VC (seen in women of both races and starting in the early 20's) could not be explained by the above factors, and may therefore reflect tissue aging.

Adolescent↗