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Obstruction of the respiratory pathways, its evaluation by methods of functional examination of the lungs and development in patients with cystic fibrosis.

In 28 patients with cystic fibrosis aged 5--24 years the values of maximum expiratory flow rates (Vmax) at lower volume levels were assessed, as well as the "specific" conductance of the respiratory pathways (Gaw/TGV), the vital capacity (VC), total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC), RV/TLC and FRC/TLC ratios and the one-second forced expiration of the vital capacity (FEV1) to evaluate obstruction of the respiratory pathways. Most markedly and most frequently abnormal were the values of Vmax, RV and of the RV/TLC ratio. These findings revealed that in almost all patients with CF there was already during the initial examination an obstruction of the peripheral respiratory pathways and hyperinflation of the lungs. During repeated measurement of the above values of lung function in 15 patients with cystic fibrosis during a period of 1--5 years when the patients increased in height by 10 cm on average, the above values did not deteriorate on average. There was, however, an individual variability of the investigated values during this period. The comprehensive treatment provided in our country prevented in patients with CF a deterioration of obstruction of the respiratory pathways during the period of investigation.

Adolescent

[Examinations of the pulmonary function of untrained and physically trained old men (author's transl)].

In tests there were determined the vital capacity and absolute and relative seconds capacity of 180 physical-trained sportsmen aged 55 to 89 and of 175 untrained, but clinically healthy test persons. The results of the different age-intervals are compared statistically. It was noticed, that vital capacity and absolute seconds-capacity of both groups decrease statistically significant with the age. Vital capacity and seconds capacity are in all age-intervals on a higher level with the trained sportsmen than the control group. The relative seconds-capacity showed no significant difference between the two groups. There is a clear statistic connexion between the vital capacity and the time obtained in a 5 000 meters run. One can suppose that in contrast to juvenile sportsmen a good pulmonary function is a contributory determinant of the performance of old sportsmen.

Age Factors

An epidemiologic study of a group of talc workers.

Chest roentgenograms, pulmonary function assessment by spirometry, respiratory symptoms, smoking history, and occupational history by questionnaire were obtained from 121 male talc miners and millers exposed to talc containing tremolite and anthophyllite asbestiform fibers. Ninety-three of the employees had worked in talc only at the plant under study. Symptoms were only slightly more prevalent in talc workers when compared to potash miners. Mean pulmonary function (forced expiratory volume in one sec, forced vital capacity, and maximal expiratory flow at 50 and 75 per cent of vital capacity) of talc workers was significantly decreased in comparison to that of potash miners. The prevalence of pleural calcification and pneumoconiosis in talc workers with 15 or more years of employment was higher than in potash miners. The prevalence of pleural thickening was 31 per cent in those who worked more than 15 years and was significantly increased as compared to that in potash miners. Workers with pleural thickening had decreased pulmonary function in comparison to those who did not. Decreased one-sec forced expiratory volume and forced vital capacity were associated with exposure to respirable particulate and asbestiform fibers.

Adult

Changes in pulmonary function after naturally acquired respiratory infection in normal persons.

Changes in pulmonary function due to naturally occurring respiratory tract infection were examinated in 26 normal healthy volunteers during a period of 6 months. Forced expiratory maneuvers in each volunteer were recorded at 2-wk intervals throughout the study and daily during illness. Significant impairment of peak expiratory flow rate, forced vital capacity, forced expiratory volume in one second, and maximal mid-expiratory flow rate at 50% of the vital capacity was observed during infection, whereas changes in the maximal expiratory flow rate at 75% of vital capacity were nonsignificant. From these results, we conclude that large airways are certainly affected during uncomplicated respiratory infections in normal healthy persons and from the changes observed in FVC we suggest that more widespread involvement of the small airways may occur.

Adolescent

Role of single-breath carbon monoxide-diffusing capacity in monitoring the pulmonary effects of bleomycin in germ cell tumor patients.

Serial pulmonary function tests including single-breath carbon monoxide-diffusing capacity (DLCO), forced vital capacity (FVC), and forced expiratory volume in 1 sec were performed in a relatively homogeneous group of male patients with germ cell tumors treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum. Of the pulmonary function tests used, the DLCO was shown to be the most sensitive indicator of subclinical bleomycin pulmonary effects. Decreases in DLCO were both total dose and schedule dependent. Patients receiving their total dose of bleomycin at a rate of 25 +/- 2 (S.D.) units/week developed a linear decrease in DLCO with increasing total doses of bleomycin. Changes in FVC did not correlate with bleomycin total dose. Although both the mean DLCO and FVC decreased after completion of bleomycin therapy, the mean FVC returned to base-line levels rapidly, whereas the decrease in mean DLCO was persistent for several months. When routine volumetric tests (FVC and forced expiratory volume in 1 sec) and DLCO are used in a systematic manner, DLCO is the most sensitive indicator of the subclinical pulmonary effects of bleomycin in germ cell tumor patients treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum.

Adult

The influence of lower respiratory illness in infancy and childhood and subsequent cigarette smoking on lung function in Sydney schoolchildren.

A prospective study of respiratory illness history and lung function of 10,898 school children in Sydney was begun in 1971. At the first visit, a history of previous asthma and of bronchitis before and after the first 2 years of life was obtained from a parental questionnaire, and maximal expiratory flow-volume curves were recorded. These lung function studies were repeated yearly between 1972 and 1974, at which time a history of respiratory illness during the previous 12 months and a personal smoking history were recorded, Two groups of children from a random selection of primary and secondary schools in Sydney were studied. Their respective mean ages were 8.9 yr (primary group) and 12.6 yr (high school group) in 1971. Mean values for the maximal flow at 50 percent of the forced vital capacity were lower in children with a history of bronchitis and/or asthma than those in the control group. This was true in both age groups in both sexes. No differences were found in the 0.5-s forced expiratory volume or forced vital capacity. The differences in maximal flow at 50 per cent of the forced vital capacity were present again in 1974. In 1974, the data from smokers were compared with those from nonsmokers; small differences were found. The results suggest that bronchitis in infancy and childhood as well as asthma may affect lung function as children grow, that the abnormality may not be detected by the forced expiratory volume, that the abnormality persists, and that it is possible that the abnormality is further affected by smoking.

Adolescent

Proteomic Profiling of Pulmonary Function and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study.

BACKGROUND: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality. METHODS: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11&#x2009;354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of the identified proteins on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and mortality was estimated using logistic regression and Cox proportional hazards models. Pathway enrichment and Mendelian randomization explored underlying biological functions and causal effects. RESULTS: Of 4766 proteins analyzed, 364 were cross-sectionally associated with forced expiratory volume in 1 second (and forced vital capacity (false discovery rate<0.05). Ninety-four and 270 proteins had concordant positive and negative effects, respectively. Five pathways related to pulmonary and cardiac function were enriched. Of the 364 proteins, 112 were linked to all 4 outcomes, where 86 were associated with increased risk (odds ratio/hazard ratio [OR/HR], 1.05-1.42) and 26 with reduced risk (OR/HR, 0.69-0.96). Six proteins (STAT3 [signal transducer and activator of transcription 3], MIC-1 [growth differentiation factor 15], apoA-II [apolipoprotein A-II], TPST1 [protein-tyrosine sulfotransferase 1], integrin a1b1 [integrin alpha-I: beta-1 complex], and BLC [C-X-C motif chemokine 13]) showed potential inverse causal effects on with forced expiratory volume in 1 second and forced vital capacity, and integrin a1b1 demonstrated consistent inverse associations with chronic obstructive pulmonary disease, coronary heart disease, and heart failure risks. CONCLUSIONS: Proteins associated with pulmonary function may influence CVD risk. Six proteins, including integrin a1b1, represent promising targets for future interventions.

Aged

Effects of influenza vaccination on the peripheral airways of healthy human volunteers.

Forty-two volunteers (15 of them cigarette smokers) were studied to determine the effects on the airways that might result from immunization with killed influenza virus vaccine. The forced vital capacity, the forced expiratory volume in one second, the maximal expiratory flows at 50 and 75 percnet of vital capacity, and the volume isoflow were determined before and at 24, 48, and 72 hours and one and two weeks after vaccination. For both smokers and nonsmokers, there were no significant changes in the results of these tests of pulmonary function following vaccination.

Adult

Adaptation in human subjects to the effects of inhaled ozone after repeated exposure.

Single exposures to low concentrations of ozone (0.4 to 0.5 ppm) have resulted in decrements in forced vital capacity and specific airway conductance. To establish whether adaptation might occur with repeated exposure, 14 normal human subjects were exposed on 5 consecutive days to 0.4 ppm of ozone for 3 hours per day in an environmental chamber. Measurements of forced vital capacity and specific airway conductance obtained after exposure to ozone were compared to corresponding control values obtained during the previous week, when the same subjects breathed filtered air in the environmental chamber for 3 hours per day on 5 consecutive days at the same time of day. The forced vital capacity was significantly lower than the control value on the first 3 days of exposure to ozone, but there was no significant difference on the fourth and fifth days. Specific airway conductance was significantly lower than the control value on the first and second days of exposure to ozone; no significant difference was noted on the third, fourth, or final day. All subjects were symptomatic on the first and second days of exposure to ozone. Symptoms resolved thereafter, with only one subject remaining symptomatic on the final day of exposure to ozone.

Adaptation, Biological

Respiratory abnormalities among grain handlers: a clinical, physiologic, and immunologic study.

A survey of 300 grain elevator workers revealed that 77 per cent complained of eye symptoms; 64 per cent, of nasal symptoms; and 88 per cent, of one or more respiratory symptoms on exposure to airborne grain dust. Symptoms on exposure were independent of age and length of employment. Cough and wheezing on exposure were more common among smokers than nonsmokers (P less than 0.025). Nineteen per cent of the workers had had episodes of grain fever. The prevalence of chronic bronchitis was 37 per cent (42 per cent of smokers and 30 per cent of nonsmokers). Wheezes on auscultation were found in 23 per cent. Measurements of lung ventilatory function, as well as diffusing capacity, correlated significantly with age and smoking habits, but not with length of employment. Thirty-seven per cent of the workers had an abnormal mean forced expiratory flow during the middle half of the forced vital capacity (47 per cent of smokers and 13 per cent of nonsmokers), and 34 per cent had an abnormal maximal expiratory flow after exhalation of 50 per cent of the forced vital capacity (40 per cent of smokers and 13 per cent of nonsmokers), whereas only 13 per cent had an abnormal ratio of 1-sec forced expiratory volume to forced vital capacity. There was no correlation between precipitins to fungi, bacteria, grain, or grain dust antigens and acute or chronic respiratory symptoms, lung function, or grain fever. There was, however, a significant correlation between cutaneous reactivity to grain dust and wheezing on exposure (P less than 0.02). Abnormal flows at low lung volumes were more common among cutaneous reactors to common allergens. We concluded that exposure to airborne grain dust can cause acute inflammatory reaction to the exposed mucosa, and it is highly probable that grain dust contributes and, in some cases, causes chronic airway disease.

Adult

Dyspnea.

Dyspnea is the medical term for the patient's or subject's complaint of shortness of breath. It encompasses the respiratory discomfort experienced in many different diease states as well as the shortness of breath felt by a normal subject during or after strenuous exercise. Several parameters which have been shown to correlate with the onset or severity of dyspnea are described, including reduced vital capacity, the ratio of minute ventilation to vital capacity, reduced breathing reserve, the work of breathing, and the oxygen cost of breathing. Attempts at quantitation of dyspnea have usually consisted of measuring physiological parameters associated with the sensation, such as the "dyspneic index". The direct measurement of respiratory sensations using modern psycho-physical methods is at an early stage of development. Since the observation that the existence of dyspnea is often unrelated to any disturbance of arterial blood gas composition, it has been generally held that the mechanism of dyspnea is primarily neurophysiological. The neural pathways may conceptually be divided into those which transmit the "dyspnea message" from the respiratory apparatus to integrating centers in the brain, and those concerned with subsequently bringing the sensation to the level of consciousness. It seems likely that there is no single sensing mechanism and neural pathway which will be able to explain dyspnea in the diverse populations of patients and subjects who experience unpleasant respiratory sensations. Three theories concerning mechanisms of dyspnea are briefly described: "length-tension inappropriateness", vagal afferent activity especially from the J-receptors, and the recent concept of diaphragmatic fatigue. Some specific characteristics of the shortness of breath experienced in certain disease states are described, including chronic bronchitis and emphysema, bronchial asthma, pulmonary fibrosis and congestive heart disease.

Asthma

Human response to controlled levels of inert dust.

We studied nasal mucous flow, airway resistance, and subjective response in 16 young healthy subjects during 5-hour exposures to 2, 10, and 25 mg of inert dust per m3 in an environmental chamber. The dust was a fully polymerized plastic dust containing carbon black. The number of these particles in room air, expressed as a per cent of the total number of particles was 36, 41, 14, 7, and 2, respectively, for the aerodynamic size ranges less than or equal to 1.8, 1.9 to 5.3, 5.4 to 8.9, 9.0 to 12.4, and greater than or equal to 12.5 micron. No significant changes in nasal mucociliary clearance rate or nasal resistance were observed. At all dust concentrations there was a decrease in 1-sec forced expiratory volume, but not in the forced vital capacity or the forced expiratory flow during the middle half of the forced vital capacity. The nasal penetration fraction of particles was approximately 55 per cent for the smallest particles and 20 per cent for the largest particles. Discomfort was proportional to the concentration of dust, but lagged almost 2 hours behind the changes in dust concentration. The discomfort was never excessive; the main complaints were dryness in the nose and pharynx.

Adult

Forced expiratory spirometric parameters derived by feature-extraction techniques.

Spirometric data from 200 patients seen in the pulmonary function laboratory were analyzed retrospectively. Using standard criteria, the spirometric patterns of the subjects were classified as indeterminate, normal, restrictive, or obstructive; obstruction was further classified as mild, moderate, severe, or very severe. A formal feature-extraction technique was used to define 2 new parameters. These were linear combinations of the 5 standard spirometric parameters and explained 94% of the variation in the original parameters. The derived parameters provided better separation of the various classes than the combination of the normalized forced vital capacity and the ratio of the forced expiratory volume in 1 s to the forced vital capacity.

Forced Expiratory Flow Rates

Small airways in progressive systemic sclerosis (PSS).

Obstructive disease involving peripheral airways has been noted in diffuse interstitial pulmonary disease, including sarcoidosis and cryptogenic fibrosing alveolitis. The possibility of obstruction of small airways in progressive systemic sclerosis (PSS) has been suggested by widespread bronchiolectasis and peribronchial fibrosis noted at necropsy. We performed pulmonary function studies in 39 subjects (22 nonsmokers and 17 smokers) with PSS, most of whom had functional evidence of interstitial pulmonary involvement (increased static recoil pressure and reduced diffusing capacity). The 1 second forced expiratory volume to forced vital capacity ratio (FEV1:FVC) was normal in all subjects. Although the severity of the restrictive process was greater in nonsmokers compared with that in smokers, the maximal mid-expiratory flow rate, closing volume, closing capacity, volume of isoflow, change in maximal expiratory flow at 50 per cent of vital capacity during 80 per cent helium--20 per cent oxygen breathing compared with air breathing (delta Vmax50), ratio of dynamic to static lung compliance at different breathing frequencies and upstream airway conductance at static recoil pressures of 5 and 10 cm H2O were nearly always normal in the nonsmokers but were frequently abnormal in the smokers with PSS. These findings suggest that diffuse interstitial pulmonary disease due to PSS generally does not lead to functional evidence of obstruction in peripheral airways and that when the latter is found it can likely be attributed to the effects of concomitant cigarette smoking.

Adult

The Framingham Eye Study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study.

Using the age-sex-specific data collected in the Framingham Heart Study 1948--1964 together with ophthalmic diagnoses made in the Framingham Eye Study in 1973--1975, the following variables were found to be associated with senile cataract: education, casual blood sugar, systemic blood pressure, height, vital capacity, serum phospholipid and hand strength; with senile macular degeneration: systemic blood pressure, height, vital capacity, left ventricular hypertrophy, hand strength and history of lung infection; with diabetic retinopathy: casual blood sugar, urine sugar and other specific elements of diabetes; with ocular hypertension: systemic blood pressure, height, casual blood sugar and pulse rate. No variables were identified as associated with open-angle glaucoma. The paper stresses the need for corroboration of these findings, which may be a mix of real and chance associations, and the need for additional analyses before any of these associations are considered evidence of factors related to risk of ophthalmic disease.

Aged

Positive end-expiratory pressure in weaning patients from controlled ventilation. A prospective randomised trial.

Twenty-five patients in acute respiratory failure were randomised to receive either 5 cm of positive end-expiratory pressure (P.E.E.P.) or no-P.E.E.P. while weaning from controlled ventilation. The use of P.E.E.P. resulted in a significant reduction in the increase in alveolar-arterial oxygen tension gradient (AaDO21) which occurred in the group of patients who were converted from controlled ventilation to spontaneous ventilation without P.E.E.P. Patients who weaned without P.E.E.P. had a mean increase in AaDO21 of 102+/-35 mm Hg S.E. while those who weaned with P.E.E.P. had a mean increase of only 10+/-22 mm Hg (P less than 0-03). The use of P.E.E.P. was also associated with a significant improvement in the vital capacity and the maximum inspiratory force. Patients who weaned with P.E.E.P. had an increase in vital capacity of 258+/-108 ml (P less than 0-05) and an increase in inspiratory force of -15+/-5 cm H2O (P less than 0-01), while patients who weaned without P.E.E.P. did not have significant changes in these measurements. The use of P.E.E.P. during weaning may be helpful in patients who fail to wean because of the development of hypoxaemia due to rapid alveolar collapse, since P.E.E.P. appears to minimise the increase in intrapulmonary right-to-left shunt which normally occurs during weaning from controlled ventilation.

Acute Disease

[Effects of beta blockaders on ventilatory function in chronic bronchitis].

This study was carried out to determine whether beta blockers could be prescribed for patients with coronary insufficiency and chronic bronchitis. The effects of intravenous infusions (30 mn) of propranolol (30 micrograms/kg), practolol 90 micrograms/kg), atenolol (90 micrograms/kg) and acebutolol (150 micrograms/kg) on vital capacity and expiratory flow rates were investigated in chronic bronchitics. Propranolol (n = 51) moderately reduced the vital capacity and FEV1, by an average 9% and a maximum of 20%. The three other infused agents given to groups of 10 patients did not change the ventilatory function. When the same patients were investigated by cross over with propranol bronchoconstriction was observed. This effect was seen in all stages of chronic bronchitis but was much less severe than in a group of 50 asthmatic patients (-23%). The respiratory tolerance of the cardioselective beta blockers seems to be better but there is considerable individual variation and the diagnosis between asthma and chronic bronchitis may itself be very difficult.

Acebutolol

Response of asthmatic patients to fenoterol inhalation: a method of quantifying the airway bronchodilator dose.

A radiotracer technique is described which enables direct measurement of the dose and distribution of inhaled aerosol bronchodilator in man. The mean (+/-SD) amounts of the B2-adrenergic agonist, fenoterol, administered to a group of 12 asthmatic subjects in a double-blind randomized fashion were: placebo, 0 microgram; low dose, 5.6 (+/-1.2) microgram; medium dose, 32.7 (+/-7.3) microgram; and high dose, 127.5 (+/-29.2) microgram, with a mean of 86.3% of the total subject dose being deposited in the lungs. The medium and high doses of fenoterol produced similar increases above baseline in forced expired volume in 1 sec (FEV1), maximum flow at 50% of vital capacity (V max 50), and maximum flow at 25% of vital capacity (V max 25). These increases were greater than those with placebo for the entire 4-hr study (p less than 0.01). The low dose of fenoterol was more effective than placebo in increasing FEV1, V max 50, and V max 25 above baseline values (p less than 0.05), but not for the entire 4-hr study. The high-dose fenoterol caused palpitations and tremor in 3 of the 12 subjects, and the medium-dose fenoterol caused palpitations in one of these subjects.

Adult