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Biomedical subjects

R J Knudson

Publications and source records attributed to R J Knudson.

At least 55 records · Page 3Linked to original sources
PubMed1979

Assessment of alpha-1-antitrypsin deficiency heterozygosity as a risk factor in the etiology of emphysema. Physiological comparison of adult normal and heterozygous protease inhibitor phenotype subjects from a random population.

For plethysmographic studies of lung mechanics and measurement of pulmonary diffusing capacity, 62 subjects were drawn from a randomly selected population sample. Data obtained from the 24 subjects of heterozygous phenotype for alpha-1-antitrypsin deficiency (PiMZ) were compared by age group with data from 38 normal (PiM) subjects matched for sex, age, and smoking history. Comparison of mean values by age group for lung volumes, diffusing capacity, lung elastic recoil, maximum expiratory flow, and the occurrence of frequency dependence of dynamic compliance revealed no differences between phenotype groups. There was no evidence of an accelerated effect of aging among PiMZ subjects when compared with normal counterparts nor was there evidence of an increased effect of smoking. From these data it appears that the PiMZ phenotype per se is not a risk factor in the development of emphysema.

Adult↗
PubMed1979

Spirometric testing. Number of tests required and selection of data.

To address the questions of whether three or five maneuvers for forced vital capacity (FVC) should be required for adequate spirometric testing and whether the largest or mean values for FVC and the forced expiratory volume in the first second (FEV1) should be used for analysis, we analyzed spirometric data obtained from approximately 3,000 people for each of three consecutive years. The following four algorithms for selection of data were tested: (1) the average of the best two of five measurements; (2) the average of the best two of the first three; (3) the best of five; and (4) the best of the first three. There were no significant differences between any two algorithms within a given year and no differences between any two years for any algorithm. We conclude that there is little to be gained by requiring more than three maneuvers for FVC or in using values other than the largest FEV1 and FVC.

Adolescent↗
PubMed1978

Closing volume and flow volume abnormalities in alpha(1)-antitrypsin phenotype groups in a community population.

Alpha1-antitrypsin phenotype groups, found in a community population studied in Tucson, were compared by using the maximum expiratory flow volume curve and the single-breath nitrogen test, alone and in combination. Subjects 25 to 54 years of age were used for the comparison, among whom there were 728 Pi M, 29 Pi MZ, and 62 Pi MS phenotypes. None of the flow volume parameters or closing volume parameters was able to differentiate among the phenotype groups; subjects in groups heterozygous for alpha1-antitrypsin did not differ from individuals homozygous for Pi M with regard to any or all flow volume or closing volume parameters.

Adult↗
PubMed1977

Relation of protease inhibitor phenotypes to obstructive lung diseases in a community.

To examine the relative risk for the development of obstructive lung disease in persons heterozygous for alpha1-antitrypsin deficiency, we determined protease inhibitor phenotypes in 2944 subjects in a general community population. Phenotype M was found in 89.5 per cent, MS in 7.1 per cent, and MZ in 3.0 per cent of the population. There were two persons of phenotype Z and six of phenotype SZ. The study also included respiratory questionnaires and spirometry. There were no statistically significant differences in the prevalence of respiratory symptoms and diagnoses or of ventilatory impairment among the three major phenotype groups (M, MS and MZ), nor were there differences in the rates of deterioration of function with age or smoking. Consequently, we do not consider population screening for heterozygous alpha1-antitrypsin deficiency to be worthwhile.

Adolescent↗
PubMed1977

Effect of aging alone on mechanical properties of the normal adult human lung.

For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25-75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were alpha1-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25-35, 36-64, and 65-75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly.

Adult↗
PubMed1977

Quantitative relationships between cigarette smoking and ventilatory function.

In this study of a general population sample, highly significant quantitative relationships were noted between pack-years of smoking and functional impairment. Subjects with chronic productive cough showed steeper declines in the forced expired volume in 1 sec and forced expiratory flow after exhalation of 75 per cent of the forced vital capacity (Vmax 25), but a definite inverse relationship between ventilatory function and pack-years was demonstrated even among subjects who denied any cough or sputum production. Current smoking showed no relationship to 1-sec forced expiratory volume or Vmax 25 when total pack-years were taken into account. Age appeared to be an important independent determinant of per cent predicted values only in regard to the Vmax 25 in symptomatic nonsmoking women. A history of childhood respiratory trouble was associated with a lower ventilatory function regardless of smoking habits, and for this reason such subjects have been deleted from detailed analyses of dose-effect relationships. Allergy skin test reactivity in young to middle-aged adults showed a significant additive effect to pack-years as a determinant of forced expiratory flow toward the end of the forced vital capacity, but the effect was noted only among present smokers.

Age Factors↗
PubMed1977

The closing volume test: evaluation of nitrogen and bolus methods in a random population.

The closing volume test, using helium bolus and nitrogen washout techniques simultaneously, was evaluated in more than 1,900 persons randomly selected as representative of the white population of Tucson, Arizona. Normal values were based on data obtained from those totally asymptomatic persons who had never smoked cigarettes. In the remaining population, the slope of Phase III appeared to be more sensitive than any other measurement in detecting abnormalities, but all measurements taken in conjunction were superior to any single parameter. Closing volumes measured by the bolus method were systematically greater than those obtained by resident nitrogen technique in normal subjects and were slightly more sensitive in detecting abnormalities in other population subgroups. Nevertheless, the single-breath test was of only limited value in distinguishing asymptomatic smokers from nonsmokers. Parameters used in conjunction revealed abnormalities in 36% of symptomatic subjects, many of whom already had physician-confirmed obstructive pulmonary disease. Our data suggest that, when applied to a randomly selected population, abnormalities in the closing volume test occur in only a very small proportion of persons in whom a respiratory disorder would not otherwise be suspected or already diagnosed.

Adolescent↗
PubMed1977

The relationship of childhood respiratory illness to adult obstructive airway disease.

This study of a general population sample reveals close relationships between histories of childhood respiratory disorders and pevalences of symptoms, obstructive airway diseases, and ventilatory impairment in 2,626 adults more than 20 years of age. Although a history of pediatric respiratory illness is associated with relatively mild impairment of ventilatory function in young adults, subjects with such a history shown an excessive decline in function with advancing years and with cigarette use. Because some of the data are retrospective and subject to the bias of preferential recall of childhood events, these observations cannot be regarded as definitive. However, present observations are compatible with the hypothesis that pediatric respiratory illness represents an important risk factor for the development of obstructive airway diseases in adult life. It is suggested that these childhood respiratory illnesses cause the adult lung to be unusually susceptible to the adverse effects of a variety of bronchial irritants and infectious agents.

Adolescent↗
PubMed1977

Comparison of flow-volume and closing volume variables in a random population.

Data obtained from results of single-breath N2, or closing volume, tests were compared with maximal expiratory flow-volume parameters in 725 subjects, 25 to 54 years of age, from a random, stratified, cluster sample of the population of Tucson, Arizona. Results of the 2 tests showed poor concordance. A greater proportion of abnormalities was revealed by maximal expiratory flow-volume measurements than by the single-breath N2 test in population subgroups defined as other than "normal". Among the 114 subjects reporting physician-confirmed asthma, chronic bronchitis, or emphysema, less than one half of those with maximal expiratory flow-volume abnormalities also had an abnormality in the single-breath N2 test. Results of this comparison do not indicate that the closing volume test, when applied to a general population, consistently reveals abnormalities of clinical significance.

Adult↗
PubMed1977

Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis.

A syndrome characterized by hypoxemia aggravated by exercise, orthodeoxia, hypocapnia, and evidence of hyperdynamic circulation, but otherwise normal indices of pulmonary air flow, volume, and distribution of ventilation has been observed as an infrequent complication of hepatic cirrhosis. An illustrative case is described, the features of which support the presence of a shunt or shunt-like mechanism consisting of low-resistance vascular communications within the lung. We suggest that this may represent the existence of a hepatopulmonary syndrome analogous to the hepatorenal syndrome.

Arteriovenous Anastomosis↗
PubMed1976

The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age.

From a randomly selected population representative of the white population of Tucson, Ariz., satisfactory flow-volume data were obtained for 3,115 persons. Data from the 746 subjects who were totally free of symptoms or history of cardiorespiratory disease and who had never smoked were used in determining "normal" prediction equations for spirometric parameters and maximal expiratory flows. The maximal expiratory flow-volume curve showed considerable intersubject variability, but little change in shape of the mean maximal expiratory flow-volume curve was seen with advancing age when the effects of disease, insult, or injury were excluded.

Adolescent↗
PubMed1976

The maximal expiratory flow-volume curve: its use in the detection of ventilatory abnormalities in a population study.

Flow-volume and spirometric parameters obtained in a randomly selected population were examined with regard to their sensitivity in detecting abnormalities among persons who smoked and/or had respiratory symptoms. Data obtained from subjects who were totally free of cardiorespiratory symptoms and who had never smoked cigarettes were used to develop "normal" prediction equations. Using as normal limits the per cent of predicted value above which 95% of these "normal" subjects fell, maximal expiratory flow at 75% of the expired vital capacity (Vmax75) detected the greatest proportion of abnormalities in the remainder of the population. When examined according to age, however, Vmax75 was most sensitive in older subjects, whereas 1-sec forced expiratory volume was superior in younger subjects. There was a slight tendency for Vmax75 to be affected in subjects with reactive airway syndromes and for the 1-sec forced expiratory volume to be affected in heavy smokers or subjects with chronic productive cough. If one parameter was markedly abnormal, the entire flow-volume curve was likely to be affected, but concordance of the parameters examined was not complete. For the latter reason, considerable caution must be exercised in attempting to use multiple parameters in defining abnormality, unless one applies more stringent criteria for abnormality.

Adolescent↗
PubMed1975

A community study of the relation of alpha1-antitrypsin levels to obstructive lung diseases.

Since it is still uncertain whether moderate degrees of alpha1-antitrypsin deficiency predispose to the development of lung disease, data obtained from a stratified random sample of white households in Tucson, Arizona, consisting of 2586 subjects over five years of age, were analyzed. No relation was found between serum alpha1-antitrypsin levels, measured as trypsin inhibitory capacity, and ventilatory function, respiratory symptomatology, or frequency of diagnosed pulmonary diseases even among cigarette smokers. The data indicate that an intermediate level of alpha1-antitrypsin deficiency (i.e., inhibitory capacity between 20 and 62 per cent of the population's mean value) is not an important risk factor for the development of chronic obstructive lung diseases. The data militate strongly against the use of any quantitative determination of alpha1-antitrypsin as a test to identify subjects with moderate deficiency for the purpose of predicting later development of chronic respiratory disorders. The rate of severe deficiency is so low as to make population screening for such subjects impractical.

Adolescent↗
PubMed1975

Tucson epidemiologic study of obstructive lung diseases. I: Methodology and prevalence of disease.

Using a multistage stratified cluster sample of Anglo-white Tucson households (based on the 1970 Census block statistics), this longitudinal study enrolled 1655 households. The study sample of 3805 individuals thus selected representatively covered the household structures, including the age and sex subgroupings, of the Tucson Anglo-white population. The estimated prevalence rates had a very low standard error of estimate both overall and in the age- and sex-specific categories, indicating a good selection and sufficient numbers in all age-sex specific subgroups. As anticipated, prevalence rates of diagnosed respiratory and other chronic diseases were higher than those found nationally. Despite much higher rates of diagnosed pulmonary diseases within the age-sex populations over the age of 40, the results of this study are within the ranges of other surveys in terms of prevalence of many common chronic respiratory symptoms. Reasons for this apparent discrepancy are so far undertermined.

Adolescent↗
PubMed1975

Effect of muscle constriction on flow-limiting collapse of isolated canine trachea.

Before and after trachealis muscle contraction, induced by application of acetylcholine, the relationship of changing pressures to flow through excised canine tracheas was examined in a mechanical model simulating isovolume pressure-flow relationships in vivo. At the same time, the change in cross-sectional lumen area at a point in the downstream third of the trachea was measured using slit-lamp transillumination and cinematographic measurements. Trachealis muscle contraction reduced the uncompressed lumen area but inhibited dynamic collapse as driving pressures increased. As a result, following contraction, the initial slope of the tracheal pressure-flow (TPF) curve changed, indicating increase in resistance at low flows, but higher flows were achieved at higher driving pressures. Results suggest that smooth muscle tone of large airways may affect maximum expiratory flow (Vmax) and explain apparent discrepancies between in vivo measurements of resistance and Vmax. The magnitude of the Bernoulli effect contributing to airway narrowing was demonstrated by measurements of lateral airway pressures well in excess of driving pressure.

Acetylcholine↗