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Family study of alpha 1-antitrypsin deficiency: effects of cigarette smoking, measured genotype, and their interaction on pulmonary function and biochemical traits.

To gain insight into the variable expression of lung disease in alpha 1-antitrypsin (alpha 1AT) deficiency, five quantitative variables including forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75), total serum alpha 1AT, oxidized serum alpha 1AT, and total serum immunoglobulin E (IgE) were measured in alpha 1AT deficient individuals and their families. The effect of a known, measured genotype (the Pi type) was estimated for each quantitative trait; the influence of mode of case ascertainment on the measured genotype effect was also assessed. These analyses showed that total alpha 1AT levels are strongly influenced by Pi type; IgE levels are unaffected by Pi type; and FEV1, FEF25-75, and oxidized alpha 1AT are moderately influenced by Pi type. The effect of genotype-by-environment interaction between Pi type and pack-years of cigarette smoking on the five quantitative phenotypes was studied using an analysis of covariance. Significant Pi x pack-years interaction was evident for FEV1, but this effect is confounded in this data set with the Pi x age interaction. Probands who were ascertained because they had chronic obstructive pulmonary disease (COPD) do not demonstrate the significant Pi x pack-years interaction effect of the Pi x pack-years subjects ascertained for other reasons demonstrate. The effect of the Pi x pack-years interaction on FEV1 was no longer significant on a transformed scale, (FEVf12,) thus providing an additive scale for future data analysis. The increased sensitivity of Pi MZ individuals in our sample to cigarette smoking reduced the Pi x packs-years interaction effect on FEF25-75 to borderline significance. This investigation has provided an opportunity to incorporate both measured genotype and genotype-by-environment interaction analyses into the study of the variable expression of lung disease in Pi Z individuals.

Family↗

Flexible bronchoscopy: a safe method for metal stent implantation in bronchial disease.

BACKGROUND: Endoscopic bronchoplastic procedures, such as metal stent implantation, are for safety reasons and mainly performed using rigid bronchoscopy. Major complications, such as bleeding and accidental airway occlusion, are thought to be better managed with the rigid device. An increasing number of pneumologists, however, use the flexible fiberscope for endobronchial stenting. METHODS: Sixty-five stent implantations were performed in 51 patients with flexible fiberoptic bronchoscopy. We implanted 27 Tantalum Strecker stents (Boston Scientific Co, Watertown, MA), 20 Nitinol Accuflex stents (Boston Scientific Co) and 18 Wallstents (Schneider, Zurich, Switzerland). Underlying conditions were malignant disease in 84% and benign bronchial collapse in 16%. Sites of implantation were the trachea (45%), the main bronchi (35%), and other locations (20%). In 47 cases the patients received intravenous sedation combined with high frequency jet ventilation, and in 18 cases the patients were treated with topical anesthesia alone. RESULTS: Mean examination time was 58.3 (standard deviation 29.1) minutes. Eighty percent of patients experienced immediate clinical improvement in respiratory symptoms. Spirometric parameters (forced expiratory volume in one second, peak expiratory flow rate, forced vital capacity) increased. Complications included hypertension (17%), hypotension (12%), hypoxia (5%), bronchospasm (4%), initial displacement of the prosthesis (11%), and diameter mismatch between stent and bronchus (5%). All complications were managed safely. Relevant bleeding or asphyxia during the procedure has not been observed. Late stent migration was observed in 12% of cases. There were 3 fatalities within 30 days of stent placement which, however, were not attributed to the implantation technique. CONCLUSIONS: Flexible fiberoptic bronchoscopy is a safe and suitable method to perform endobronchial metal stent implantation. Complications were rare and not serious. Initial misplacement of the prosthesis occurred in some cases and necessitated removal and replacement within the same procedure.

Adult↗

Benign tracheobronchial stenoses: changes in short-term and long-term pulmonary function testing after expandable metallic stent placement.

PURPOSE: To determine the short- and long-term improvement in airflow dynamics in patients undergoing tracheobronchial stent placement for benign airway stenoses. METHODS: Twenty-two patients underwent 34 tracheal and/or bronchial stent placement procedures for benign airway stenoses and had the results of pulmonary function tests available. Stent placement indications included bronchomalacia after lung transplantation (n = 11), postintubation stenoses (n = 6), relapsing polychondritis (n = 2), and 1 each of tracheomalacia, tracheal compression, and histoplasmosis. Six patients underwent more than one stent placement procedure (range: 2-7 procedures). The mean forced expiratory volume in one second (FEV(1) ), forced expiratory flow rate in the midportion of the forced vital capacity curve (FEF(25-75) ), forced vital capacity, and peak flow (PF) rate obtained before stent placement were compared with those immediately after stent placement and with those measurements most remote from stent placement using the paired two-tailed test. RESULTS: All patients reported improved respiratory function immediately after stent placement. The mean FEV(1), FEF(25-75), and PF rate improved significantly (p < 0.001, p = 0.002, and p = 0.009, respectively) after stent placement. On long-term follow-up averaging 15 months after stent placement, these parameters declined despite patients' subjective sense of improvement. Segregating the population into transplant and nontransplant airway stenosis etiologies, however, FEF(25-75) and PF rate remained significantly improved (p = 0.045, p = 0.027, respectively), over the long term for the latter. FEV increased after subsequent stent placements for patients receiving multiple stents. CONCLUSION: Stent placement for benign tracheobronchial stenoses provides significant immediate improvement in airflow dynamics. Long-term improvement in airflow obstruction may be expected, and additional stent placements may further improve pulmonary function.

Adult↗

Cardiopulmonary and metabolic responses to maximum exercise and aerobic capacity in hemiplegic patients.

This study evaluated cardiopulmonary and metabolic responses to maximum exercise and aerobic capacity in hemiplegic patients and clarified the relationship between the resulting data and motor disability. Twenty patients with stroke and fifteen healthy controls were included in the study. Cardiopulmonary and metabolic responses to maximum exercise were investigated with an electronically braked arm crank ergometer. Vital capacity, forced expiratory volume in 1 second, peak expiratory flow rate, forced vital capacity, maximum voluntary ventilation, peak power output, respiratory exchange ratio, and exercise time were reduced in stroke patients when compared with the controls. No relationship was found between these data and motor disability. The hemiplegic patients showed a significant respiratory dysfunction and reduced exercise tolerance. These findings suggest that a program of ventilatory and aerobic training should be considered early after stroke to avoid cardiorespiratory problems and deconditioning.

Adult↗

Pulmonary function tests in cirrhotic and non-cirrhotic portal hypertension.

OBJECTIVE: To determine pulmonary functions in portal hypertension of different etiologies and with various grades of ascites. SETTING: Gastrointestinal clinic in a large community based and secondary referral hospital. PATIENTS AND METHODS: Forty five patients with portal hypertension, including 19 cirrhotics with tense ascites, 8 with moderate ascites, 6 with no ascites and 12 patients with non-cirrhotic portal hypertension. All patients underwent basal pulmonary function testing by spirometry and helium dilution technique, and arterial blood gas estimation and measurement of ascitic fluid pressure. Patients with tense ascites underwent paracentesis of up to 2 liters following which ascitic fluid pressure and pulmonary functions were estimated again. MAIN RESULTS: In cirrhotic patients without ascites, FVC (forced vital capacity), RV (residual volume), TLC (total lung capacity) and FRC (functional residual capacity) were lower than predicted values. In patients with ascites, FVC, FEV1 (forced expired volume in one second) and FEF25-75 (forced expired volume in one second) and FEF25-75 (forced expiratory flow rate between 25% and 75% of forced vital capacity) were significantly lower as compared to predicted values. FVC, FEV1, FEF25-75, pO2, pCO2 and SaO2% decreased significantly with increasing ascites. Paracentesis in patients with tense ascites led to clinical improvement and significantly improved lung volumes. CONCLUSIONS: Pulmonary functions are impaired in patients with cirrhosis, and ascites causes further deterioration. Patients with non-cirrhotic portal hypertension have normal pulmonary functions.

Adult↗

Reliability of plethysmography, the single breath oxygen test, and spirometry in population studies.

Three thousand five hundred and twenty-eight residents of a census tract in Los Angeles, California underwent pulmonary function testing in a mobile laboratory (the Breathmobile). Tests included respiratory questionnaire, electronic spirometry, the single breath O2 test and body plethysmography. The reliability and sensitivity of the tests performed in the Breathmobile was measured by repeating the same tests and others on a 3% probability sample at the University of California at Los Angeles Pulmonary Function Laboratory. The reliability of the FVC and FEV1 was excellent; of the FEF 25-75% and the FEF 50-75% -- good; and of the VTG, RA and delta N2 -- reasonably good. As yet the reliability of the closing volume fraction is inadequate in our study. Grouping by individual reported symptom complexes identified different groups of people. The questionnaire and the forced expiratory flow rates identified the most people as having decreased respiratory function. Selection of the best breath or average of the two best breaths affected results of spirometry very little.

Adolescent↗

Lung function in young adults: evidence for differences in the chronological age at which various functions start to decline.

In order to gather prospective information on the chronological age at which lung functions start to decline, follow-up measurements were carried out on 38 young adults (30 men and eight women) whose respiratory and cardiac function had been studied previously in the course of a survey of high school students. In the 15 subjects who had reached adult height at the time of the first study, only the vital capacity showed no change between studies, while forced expiratory flow rates (FEV1, MMEF), transfer factor (TLCO) and alveolar volume (VA) all decreased. By contrast, in the 23 subjects who had grown in stature since the previous tests, there was an increase in the slow and forced vital capacity, no consistent change in FEV1 and MMEF, and a decrease in TLCO. The findings are consistent with the view that the age-related decline does not start at the same chronological age for all lung functions, and suggest that structural changes associated with biological "aging" affect some functions before others. The results also illustrate the inadequacy of predicting values for early adulthood by backward extrapolation from later decades or forward extrapolation from the teens, and underline the need for comprehensive studies to elucidate the pattern of change which accompanies growth, maturation, and early adulthood.

Adult↗

Analysis of antigen-induced changes in pulmonary mechanics in sensitized inbred rats.

An inbred line of rats was derived which develop marked and consistent dyspnea following sensitization and then exposure to aerosolized antigen. This pulmonary response was investigated in detail by determining forced pulmonary mechanics to derive respiratory rate, peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in 0.1 s (FEV0.1), and maximal midexpiratory flow rate (MMFR). Challenging anesthetized rats for 5 min with an aerosol of 3% egg albumin produced minimal change in respiratory rate, a 20% fall in PEFR, a 50% fall in FVC, and a 30% decrease in FEV0.1 and MMFR. The response could be inhibited or reversed by salbutamol (0.5 mg/kg, i.v.) and aminophylline (25 mg/kg, i.v.) administered either before or after challenge. The pulmonary changes are consistent with antigen-induced asthma in the rats. The response shows similarities to human asthma and may provide a relevant experimental model.

Albuterol↗

Pulmonary function in patients with diabetes mellitus.

The present study was carried out to assess the lung functions in oral medicated and insulin administered patients with normal controls. 20 subjects were selected as the study group for oral medication (Group I), 20 subjects were selected as the study group for insulin treatment (Group II) and 40 subjects were selected as normal controls. Age group of Group I and Group II were 51.25 +/- 6.28 and 50.8 +/- 6.56 respectively and controls were age and height matched. Seventeen patients of Group I were undergoing treatment for the last 10-20 years and 20 patients in Group II were undergoing treatment for the last 30 years. Only male subjects were selected for the study. Lung function test were carried out with Spirometer (Vitallograph Compact II). A significant reduction in forced expiratory volume/forced vital capacity (FEV1/FVC%) was observed in oral pills used subjects and insulin administered subjects as compared to controls. Significant decrease in forced expiratory flow rate (FEF25-75%) in group I subjects was also observed as compared to controls. Forced mid flow time (FMFT) showed a significant increase in group II in comparison to controls. These changes clearly show the expiratory flow rates are reduced both in orally medicated and insulin administered patients. Increase in FMFT in group I may be due to the reduced respiratory ability to carry out the FVC test along with the side effects of oral medication for diabetes mellitus.

Administration, Oral↗

Characterization of spirometric function in residents of three comparison communities and of three communities located near waste incinerators in North Carolina.

Waste incinerators are an increasingly common means of solid waste disposal. However, little is documented about the physical health of community members who live close to incinerators. During a 3-yr epidemiological study, spirometric lung function was tested once annually among residents from 3 communities surrounding a hazardous waste, biomedical, or municipal incinerator and among residents in 3 comparison communities. A total of 1,016 nonsmoking individuals, aged 8-80 yr, participated during at least 1 of the 3 yr of the study; 358 individuals participated all 3 yr. Daily air-quality sampling was done for 1 mo/yr in all 6 communities. The average monthly concentrations of particulate matter with diameters of 2.5 microns and less (PM2.5 [range = 14.6-31.5 micrograms/m3]) in all communities were similar during the 3 yr of study. The mean daily PM2.5 concentrations were significantly less than the U.S. Environmental Protection Agency's allowable 24-hr standard of 65 micrograms/m3. Individual incinerators contributed less than 2.5% of the areas' total PM2.5 levels. There was no difference in percent predicted forced vital capacity, forced expiratory volume in 1 sec, or forced expiratory flow rate over the middle 50% of the forced vital capacity among members of the incinerator communities, compared with nonincinerator communities, and there were no significant differences in lung function within the 3 sets of communities. There was no evidence from this study that an association existed between residence in these 3 waste incinerator areas, which met state and federal emissions regulations, and average spirometric pulmonary function of nonsmoking community members.

Adolescent↗

Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy.

We studied the effect of prenatal maternal cigarette smoking on passive expiratory mechanics in 53 healthy infants tested early in infancy (mean +/- SD, 5.1 +/- 1.5 weeks). Maternal smoking was measured by: 1) questionnaire reports of the number of cigarettes smoked per day; and 2) urine cotinine concentrations (corrected for creatinine) at each visit. Respiratory system mechanics were assessed by the single-breath occlusion-passive-flow-volume maneuver. In ten infants born to smoking mothers the time constant of the respiratory system was 23% reduced [0.34 vs. 0.44 s; 95% confidence interval (CI), -45% + 1%; P = 0.06]. This was related to an estimated 13% decrease in respiratory system compliance (4.86 vs. 5.62 mL/cmH2O; 95%CI, -33% + 6%; P = 0.18) and a 10% reduction in respiratory system resistance (0.073 vs. 0.081 cm H2O/mL/s; 95%CI, -42% + 22%; P = 0.56). Functional residual capacity (FRC), measured by helium-dilution, was also decreased by 13% (78 vs. 90 mL; 95%CI, -27% + 0.3%; P = 0.06) in smoke-exposed infants. Forced expiratory flow rates at FRC obtained by thoraco-abdominal compression were reduced by 28% in infants of smoking mothers (VFRC, 99 vs. 138 mL/s; 95%CI, -54% + 2%; P = 0.04) as reported previously in a larger sample from this population. This study was limited by small numbers of infants exposed to smoking during pregnancy and by ethnic imbalance among the smoking-exposed and unexposed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lung function in childhood. III. Measurement of airflow resistance in healthy children.

Indices of airflow resistance have been obtained in a group of 248 healthy London schoolchildren from recordings of peak expiratory flow rate (PEFR), forced expiratory volume in 0-75 seconds (FEV 0-75) and maximum mid-expiratory flow (MMEF) and two more direct methods, airways resistance (Raw) measured plethysmographyically and total respiratory resistance (PT) by the forced oscillation technique. The normal data are presented.

Adolescent↗

Suppression of ventricular ectopy with intravenous metoprolol in patients with chronic obstructive pulmonary disease.

Intravenous metoprolol, 0.2 mg/kg, was given to 11 patients with stable, partially reversible chronic obstructive pulmonary disease (COPD) and frequent ventricular ectopic depolarizations (VEDs). The frequency of VEDs during 8 h of continuous ECG recording was reduced from a mean of 214/h to 86/h (p less than .001). Four/11 patients had a greater than 90% reduction in VEDs. There were no adverse clinical effects during the period of drug administration. However, metoprolol produced small declines of 14% in the forced expiratory volume in 1 sec (FEB1) and 21% in the forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF25-75). These data suggest that iv metoprolol is effective in reducing the frequency of VEDs in patients with COPD, although the extent of reduction in VEDs shows considerable interindividual variation. Metoprolol can be administered iv without inducing clinical bronchospasm in most patients.

Aged↗

Relationship between nasal resistance and airway hyperreactivity following nasal provocation with Dermatophagoides pteronyssinus in allergic rhinitis.

To determine whether nasal allergic symptoms can cause bronchial hyperresponsiveness to methacholine, 30 subjects with allergic rhinitis (22 with allergic rhinitis and 8 with allergic asthmatic rhinitis) were studied. All subjects were skin test positive to Dermatophagoides pteronyssinus (DP) and underwent nasal allergic provocation with DP. After provocation, there was a severe nasal allergic reaction in the challenged nostril with a significant increase in nasal resistance both immediately and long (7 h) after DP exposure. There were no significant changes in the forced expiratory volume in 1 s and the forced expiratory flow rate between 25 and 75% of the forced vital capacity and in both allergic rhinitis and allergic asthmatic rhinitis patients. There was also no change in bronchial hyperresponsiveness to methacholine. The eosinophil counts, leukotriene B4, leukotriene C4 and platelet-activating factor levels in nasal discharges also showed no differences in both groups of patients. Our studies suggest that nasal provocation with limited allergen is a safe diagnostic technique. However, the relationship between nasal resistance and airway hyperreactivity is not obvious in this study. The similar concentrations of nasal inflammatory mediators in both allergic rhinitis and allergic asthmatic rhinitis indicate that bronchial hyperreactivity is not solely due to nasal drainage of inflammatory mediators.

Adolescent↗

Effects of blasting fumes on exposure and short-term lung function changes in tunnel construction workers.

OBJECTIVES: This study attempts to determine the effects of exposure to blasting fumes and its influence on the lung function of tunnel workers. METHODS: Two groups of tunnel workers, one using ammonium nitrate fuel oil (ANFO) as the explosive and the other using size-sensitized emulsion (SSE), with 24 workers per group, were compared with a reference group (N=34) with low exposure. Spirometry was used to determine lung function. Personal exposure to total and respirable dust, alpha-quartz, volatile organic compounds, oil mist and vapors, formaldehyde, nitrogen dioxide, and carbon monoxide was measured. RESULTS: The ANFO workers were more exposed to all the agents than the reference group and more exposed than the SSE workers to all the agents except total dust and carbon monoxide. The SSE workers were significantly more exposed to total dust and alpha-quartz than the reference group. High peak exposures to nitrogen dioxide (up to 20 ppm) occurred for the ANFO workers in contrast to the SSE workers, whose exposure did not exceed 2 ppm. The lung function of the ANFO workers significantly decreased by 3% for forced vital capacity, 7% for forced expiratory volume in 1 second, and 8% for forced expiratory flow rate from 25% to 75% of the forced vital capacity over the 11-day period. The changes were reversible. There were no significant changes among the SSE workers and the outdoor workers. The ANFO workers had a significant decrease in FEV1.0 when compared with both the SSE and outdoor workers. CONCLUSIONS: Tunnel workers using ANFO explosive show a temporary reduction in lung function, whereas those using SSE do not. The most likely explanation for the observed changes is peak exposures to nitrogen dioxide.

Adult↗

Genetic factors in nonspecific bronchial hyperreactivity. An epidemiologic study.

We tested bronchial reactivity to carbachol in 50 asthmatics, healthy parents of 40 asthmatic children, and 70 healthy subjects with no personal or family history of asthma. Stepped doses of carbachol (0.1%) aerosol were given until a 50% drop in forced expiratory flow rate from 25% to 75% was observed, or until the subject had inhaled 80 of his or her own vital-capacity equivalent volumes of the aerosol. The area under the dose-response curve was computed. Histograms of the carbachol reactivity showed a bimodal distribution: 10% of normal subjects and 50% of nonasthmatic parents had values in the asthmatic range. In 85% of parent couples at least one of the two parents had bronchial reactivity without being asthmatic. Our findings suggest that bronchial reactivity to a cholinergic bronchoconstrictor indicates an autosomal-dominant pattern of inheritance.

Adolescent↗

Pulmonary function tests in beta thalassemia.

To study pulmonary function tests (PFT) in multiple transfusion recipient thalassemics, PFTs were done for 30 thalassemics and 20 matched controls. Confirmed cases of thalassemia on regular transfusion therapy were the subject of study. Apart from history and physical examination of the thalassemics, serum ferritin estimation and spirometry were done. Parameters studied included lung volumes--functional residual capacity (FRC), forced vital capacity (FVC), residual volume (RV) and total lung capacity (TLC); and flow rates--forced expiratory volume in one second (FEV1), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), peak expiratory flow 25-75 (PEF 25-75%) and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height and weight of thalassemics were below that of age matched controls. A restrictive abnormality in PFT was found in 86.6% cases. These patients were found to have a decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional decrease in the flow rates, FEV1, PEF 25-75% and PEF with a normal (> 0.75) FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung disease and fall in DLco showed a good correlation (r = 0.7, P < .001) with the severity of restrictive disease suggesting that some intrapulmonary pathology is likely to be responsible for the restrictive pattern. None of the cases had an obstructive or mixed pattern of pulmonary dysfunction. No correlation was found between severity of restrictive disease and the serum ferritin levels. A negative correlation with degree of hepatosplenomegaly was found. No correlation was found between severity of the defect and age, number of blood transfusions received and hemoglobin at the time of doing the test. To conclude, restrictive lung disease is the predominant abnormality in multi-transfused thalassemics, which is probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not directly related to iron overload.

Adolescent↗

Lung function, respiratory illness, and passive smoking in British primary school children.

BACKGROUND: Many studies have reported a significant association between parents' smoking and reduced lung function in their children, but often the association has been found to be significant only in relation to maternal smoking. There have been few epidemiological studies on this topic in Britain. METHODS: Spirometry, in 2756 children aged 6.50-11.99 years, was carried out in a representative sample of English children, an inner city and ethnic minority sample, and a Scottish sample. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow rates of 25-75% and 75-85% (FEF25-75 and FEF75-85) were measured and standardised scores obtained separately for the English representative sample, the Scottish sample and subgroups in the inner city sample, white and Afro-Caribbean children and those originating from the Indian subcontinent. Multiple regression analyses were used to assess associations of FVC, FEV1, FEF25-75 and FEF75-85 with the passive smoking and respiratory illness, with adjustment for a large number of potential confounders. Passive smoking was defined in terms of reported number of cigarettes smoked at home by each parent. The respiratory symptoms and illnesses assessed were wheeze, asthma and bronchitis attacks, cough in the morning, and cough at any other time as reported by parents. RESULTS: Maternal smoking, but not paternal smoking, was associated with reduced FEF25-75 and FEF75-85 in boys. No association was found between passive smoking and lung function in girls, but in an analysis including both sexes the interaction of sex and parental smoking on lung function was not significant. With few exceptions, FEV1, FEF25-75 and FEF75-85 were reduced in children with wheeze and asthma attacks. CONCLUSIONS: The effect of passive smoking may depend on the close contact of a parent with a susceptible child as only maternal smoking in boys was significantly associated with impaired lung function. However, this explanation remains unsubstantiated. A parent's report of wheeze and asthma attacks in the child is reflected in reduced lung function.

Child↗