Changes in the FEV1/FVC ratio during childhood and adolescence: an intercontinental study.

In children, the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) is reportedly constant or falls linearly with age, whereas the ratio of residual volume (RV) to total lung capacity (TLC) remains constant. This seems counter-intuitive given the changes in airway properties, body proportions, thoracic shape and respiratory muscle function that occur during growth. The age dependence of lung volumes, FEV1/FVC and RV/TLC were studied in children worldwide. Spirometric data were available for 22,412 healthy youths (51.4% male) aged 4-20 yrs from 15 centres, and RV and TLC data for 2,253 youths (56.7% male) from four centres; three sets included sitting height (SH). Data were fitted as a function of age, height and SH. In childhood, FVC outgrows TLC and FEV1, leading to falls in FEV1/FVC and RV/TLC; these trends are reversed in adolescence. Taking into account SH materially reduces differences in pulmonary function within and between ethnic groups. The highest FEV1/FVC ratios occur in those shortest for their age. When interpreting lung function test results, the changing pattern in FEV1/FVC and RV/TLC should be considered. Prediction equations for children and adolescents should take into account sex, height, age, ethnic group, and, ideally, also SH.

Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction.

AIM: The prevalence of airway obstruction varies widely with the definition used. OBJECTIVES: To study differences in the prevalence of airway obstruction when applying four international guidelines to three population samples using four regression equations. METHODS: We collected predicted values for forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) and its lower limit of normal (LLN) from the literature. FEV(1)/FVC from 40 646 adults (including 13 136 asymptomatic never smokers) aged 17-90+years were available from American, English and Dutch population based surveys. The prevalence of airway obstruction was determined by the LLN for FEV(1)/FVC, and by using the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society/European Respiratory Society (ATS/ERS) or British Thoracic Society (BTS) guidelines, initially in the healthy subgroup and then in the entire population. RESULTS: The LLN for FEV(1)/FVC varied between prediction equations (57 available for men and 55 for women), and demonstrated marked negative age dependency. Median age at which the LLN fell below 0.70 in healthy subjects was 42 and 48 years in men and women, respectively. When applying the reference equations (Health Survey for England 1995-1996, National Health and Nutrition Examination Survey (NHANES) III, European Community for Coal and Steel (ECCS)/ERS and a Dutch population study) to the selected population samples, the prevalence of airway obstruction in healthy never smokers aged over 60 years varied for each guideline: 17-45% of men and 7-26% of women for GOLD; 0-18% of men and 0-16% of women for ATS/ERS; and 0-9% of men and 0-11% of women for BTS. GOLD guidelines caused false positive rates of up to 60% when applied to entire populations. CONCLUSIONS: Airway obstruction should be defined by FEV(1)/FVC and FEV(1) being below the LLN using appropriate reference equations.

Spirometry: what paper speed?

Controversy still exists regarding the paper speed necessary for accurate measurements from records of maneuvers for forced vital capacity. Twenty-four spirometric wave forms of known characteristics were plotted by a computer at 1, 2, and 3 cm/sec and were measured in random order by 12 experienced readers. We found that all readers made a surprisingly large number of major errors. The speed of the paper was found to be an important determinant for accurately measuring the forced expiratory volume in one second and the mean forced expiratory flow during the middle half of the forced vital capacity. A minimum paper speed of at least 3 cm/sec is important if spirograms are to be accurately measured by hand. Human errors in measurement may be minimized by obtaining results from at least three acceptable curves, by making duplicate reading of curves, and by making use of validated computerized measurement systems.

Comparing MiniWright and spirometer measurements of peak expiratory flow.

The accuracy and instrument variability of the MiniWright (Clement Clarke) peak expiratory flow (PEF) meter was determined with 6 of the 24 American Thoracic Society's (ATS) standard waveforms using a mechanical pump. Both room air and air heated to 37 degrees C and saturated with water vapor were used. In addition, MiniWright-determined PEF measurements were compared with those obtained using a dry rolling-seal spirometer (Ohio No. 822; Ohio Medical Products; Madison, Wis) from 75 subjects on 2 different days. The MiniWright average coefficient of variation within a waveform was found to be 2.8%. Results using heated and humidified air (body temperature, ambient pressure, and saturated with water: body conditions) were 2.5% lower than those obtained using room air. Comparisons with mechanically simulated PEF and with spirometry-determined peak flow in 75 human subjects showed that MiniWright meters over-estimated flows at lower flow rates and slightly under-estimated flows at higher flow rates. These results suggest that the new "mechanical PEF" MiniWright scale should be used instead of the "traditional" MiniWright scale.

BTPS correction for ceramic flow sensor.

Several commercially available spirometers use unheated ceramic elements as flow sensors to determine flow and calculate volume of air. The usual method of correcting the resulting flow and volume values to body temperature pressure saturated (BTPS) is to apply a constant factor approximately equal to 30 percent of the full BTPS correction factor. To evaluate the usual BTPS correction factor technique, we tested several sensors with a mechanical pump using both room air and air heated to 37 degrees C and saturated with water vapor. The volume signals used to test the sensors were volume ramps (constant flow) and the first four American Thoracic Society (ATS) standard waveforms. The percent difference in FEV1 obtained using room vs heated-humidified air (proportional to the magnitude of the BTPS correction factor needed) ranged from 0.3 percent to 6.2 percent and varied with the number of maneuvers previously performed, the time interval between maneuvers, the volume of the current and previous maneuvers, and the starting temperature of the sensor. The temperature of the air leaving the sensor (exit temperature) showed a steady rise with each successive maneuver using heated air. When six subjects performed repeated tests over several days (each test consisting of at least three maneuvers), a maneuver order effect was observed similar to the results using the mechanical pump. These results suggest that a dynamic, rather than static, BTPS correction factor is needed for accurate estimations of forced expiratory volumes and to reduce erroneous variability between successive maneuvers. Use of exit air temperature provides a means of estimating a dynamic BTPS correction factor, and this technique may be sufficient to provide an FEV1 accuracy of less than +/- 3 percent for exit air temperatures from 5 degrees to 28 degrees C.

Weight gain and longitudinal changes in lung function in steel workers.

Associations among dust exposure, smoking habits, and demographic factors and longitudinal changes of lung function were assessed among male steel workers. Cohort descriptive data analysis was conducted in 541 steel workers who had performed spirometry at least twice between 1982 and 1991 (mean follow-up, 6.1 years). The annual change (slope) in FVC, FEV1, FEV1/FVC%, and in body weight was determined by simple linear regression. The Pearson correlation coefficient between weight change and spirometry changes was calculated. Comparisons were also done in 75 pairs of steel workers matched by age, height, initial FEV1, and smoking status, but whose FEV1 declines differed by > or = 60 mL/yr. The FEV1 and FVC declined an average of 44 and 50 mL/yr, respectively, for the cohort as a whole. The FEV1 and FVC declined 52 and 54 mL/yr for current smokers, 43 and 53 mL/yr for ex-smokers, and 36 and 43 mL/yr for nonsmokers, respectively. Increasing weight was highly correlated with accelerated decline in lung function (p<0.0001). In the matched pairs, mean slopes for FVC, FEV1, and FEV1/FVC ratio were -96 mL/yr, -95 mL/yr, and -0.40%/yr for the rapid decliners; and +5 mL/yr, +10 mL/yr, and +0.10%/yr for their partners (p<0.0001). Matched pair comparisons showed that the rapid decliners averaged a 4.313 kg weight gain, while their partners gained 1.044 kg during the follow-up period. The slope of weight gain was 0.708 kg/yr for rapid decliners and 0.191 kg/yr for comparison workers (p<0.0036). Weight gain, in addition to aging and cigarette smoking, was found to be associated with the longitudinal rate of decline in FVC, FEV1, and FEV1/FVC ratio.

Simple peroperative antimicrobial chemoprophylaxis in elective neurosurgical operations.

From August 1981 to February 1982 postoperative infections due to different strains of penicillin-resistant Staphylococcus aureus occurred in 20 of 467 patients (4.3%) undergoing elective cranial and spinal operations. These infections were not attributable to defects in procedures or the theatre environment, therefore chemoprophylaxis was instituted. In the following 8 months, when patients were given penicillin G and sulphadiazine for 5 days commencing immediately postoperatively, S. aureus infections occurred in five of 579 patients (0.9%). In a subsequent randomized uncontrolled study, infections occurred in six of 265 patients receiving penicillin (2.3%), three of 270 receiving penicillin and sulphadiazine (1.1%) and one of 45 receiving erythromycin (2.2%) immediately postoperatively for 5 days. In a further study in which 587 patients received penicillin for 5 days commencing immediately preoperatively, infections due to S. aureus occurred in six (1.1%). Infections due to gram-negative organisms were seen in five (0.4%) of 1167 patients in the two uncontrolled studies.

Incidence of lower extremity deep vein thrombosis in neurosurgical patients.

In 100 patients who underwent major cranial or spinal operations, the incidence of lower extremity deep vein thrombosis was 29%. Of importance was the presence of known risk factors, particularly leg weakness and a long operation. The subject of deep vein thrombosis and its complications in neurosurgical disorders is reviewed and its prophylaxis is discussed. The administration of low dose heparin based on an epidemiological analysis of the risks involved would seem to be an effective method of prophylaxis.

Comparison of spirometric reference values for Caucasian and African American blue-collar workers.

Interpretation of lung-function test results, specifically the forced vital capacity and forced expiratory volume in one second, generally involves the comparison of these parameters with reference values based on an individual's age, height, sex, and race. Such comparisons are often used to make important decisions concerning an individual, such as job placement or disability rating. Several studies have shown that predicted values for African Americans are approximately 15% less than those for Caucasians, most likely because of the use of standing height to estimate the size of the thorax. When an adjustment for race is applied to reference values based on a Caucasian population, a single value (15%) is usually applied to all individuals. When using a group of blue-collar workers (766 Caucasian and 633 African-American subjects) without any race adjustment, 10.2% of the Caucasians and 37.4% of the African-American subjects were below the lower limit of normal. When a single adjustment factor was used, 11.5% of the African-American subjects were below the lower limit of normal. Between-subject variability within an ethnic group was far greater than variability between groups. Our results suggest that although a difference between Caucasian and African-American test results for forced vital capacity and forced expiratory volume in one second exists, an application of a single adjustment factor universally applied to all individuals, regardless of their age, sex, and height, is not optimal, and alternative approaches are needed.

Improvement in lung function measurements using a flow spirometer that emphasizes computer assessment of test quality.

We compared retrospective measurements of lung function from 101 steel workers using a commercially available spirometer to prospective lung function measurements performed, on average, 1.3 years later, with a newly developed spirometer. This spirometer was designed and developed to incorporate technology that provides immediate feedback on the quantitative and qualitative aspects of each forced expiratory effort. Of the 101 workers, 82 who had spirometry performed with each spirometer had at least two acceptable curves, and 51 workers tested with each spirometer had curves that met all American Thoracic Society (ATS) criteria for spirometry. No group showed the anticipated decline in forced expiratory volume in 1 second (FEV1) over time. The results showed an increased number of curves meeting ATS acceptability and reproducibility criteria, and a statistically significant increase in the FVC in all groups, and an increase in the FEV1 in the group encompassing all workers. Use of technology that strengthens the interaction between the spirometry technician, the data available to the technician on the computer, and the participant appears to represent true underlying lung function more accurately. Such an approach to the collection of lung function data should be considered by those evaluating spirometers for implementation in the workplace or pulmonary function laboratory as well as by those planning future spirometer development.

Quality control in the pulmonary function laboratory.

The addition of computers to pulmonary function laboratories has reduced quality-control problems. After standards for a test have been selected, the computer can enforce adherence to them. The computer can be programmed to perform periodic calibration checks and other self-diagnostic procedures to ensure that instrumentation and human errors have not gone undetected. The computer can be used to verify that reference values are within acceptable limits and that results for a particular patient are at least internally consistent. The computer greatly reduces the number of measurements and calculations that must be done by hand and therefore improves laboratory efficiency and reduces the probability of human error. Quality-control samples can be processed more frequently with the use of a computer because this task consumes less time than when done by laboratory personnel. Some disadvantages of quality control that have appeared since the introduction of the computer are the potential for undetected failure of computer hardware and software, a risk that has increased with the increase in software complexity, and the potential for the loss of large amounts of information because of its being stored on a single digital medium. To effect quality control in the pulmonary function laboratory one should (1) ensure that procedures and software conform to standards, (2) follow routine calibration-check procedures, (3) check test results for internal consistency and for consistency with other test results, (4) conduct periodic testing of a quality-control subject or reference sample, (5) continually evaluate software performance, (6) carefully evaluate changes in instrumentation and software, and (7) maintain duplicate copies of data on different types of mass storage media.

Five years' clinical experience with a leucite-reinforced porcelain crown system.

This paper reports on 5 years' experience using a leucite-reinforced porcelain crown system in a private practice setting. A total of 159 units of the porcelain were placed between November 1987 and November 1992. The porcelain can be employed in equigingival and supragingival cases, thereby reducing iatrogenic periodontal problems. The technique and theory of its use is discussed as well as its failure rate, due to fracture, in the various regions of the mouth. Three cases are presented to demonstrate the use of the porcelain.

[Multiple intracranial mycotic aneurysms. Case report]. / Múltiplos aneurismas micóticos intracranianos. Registro de um caso.

The case of a 31 years old woman with multiple intracranial mycotic aneurysms in association with subacute bacterial endocarditis is reported. The authors discuss the clinical and pathological aspects of such lesions. The complete regression of all the aneurysms after antibiotic therapy favours an approach aiming at adequate control of the infection prior to any consideration of surgical treatment.

A prominent role for the IL1 pathway and IL15 in susceptibility to chronic cavitary pulmonary aspergillosis.

Chronic cavitary pulmonary aspergillosis (CCPA) is a progressive lung condition with a 10-30% annual mortality. Although overtly immunocompetent, some immunogenetic defect in patients is likely. To investigate a possible immunogenetic defect in CCPA, we analysed biologically plausible candidate genes in 112 CCPA patients and 279 healthy controls in a genetic association study of genes involved in the post-recognition immune response to Aspergillus fumigatus. We also compared gene expression in monocyte-derived macrophages from subjects with and without disease, both at baseline and during stimulation with A. fumigatus. Compared with macrophages from healthy subjects, CCPA macrophages showed unrestrained rises in IL1A, IL1B, IL6, IRAK2 and TRAF6 throughout the experiment, and a lack of expression of TGFB1 at 9 h. Single nucleotide polymorphisms (SNPs) associated with CCPA were found in IL1B (n = 2), IL1RN and IL15 (n = 3). Uncontrolled expression of IL1 and IL6 and continuing high levels of these cytokines may result in continuing cellular influx and pro-inflammatory responses, inhibiting disease resolution and contributing to disease progression in CCPA. The association of SNPs in IL1B, IL1RN and IL15 with CCPA supports a role for the IL1 pathway, as well as implicating the IL15 gene, in susceptibility to CCPA.

Reduced expression of TLR3, TLR10 and TREM1 by human macrophages in Chronic cavitary pulmonary aspergillosis, and novel associations of VEGFA, DENND1B and PLAT.

Chronic cavitary pulmonary aspergillosis (CCPA) is an uncommon but serious pulmonary disease of humans, with an annual mortality rate of 10-30%. It is caused by the fungus Aspergillus fumigatus. Patients are overtly immunocompetent; however, some immunogenetic defect is likely. To investigate this, we performed a genetic association study analysing biologically plausible candidate genes in 112 CCPA patients and 279 healthy controls, and investigated gene expression in monocyte-derived macrophages from patients and controls at baseline and during stimulation with A. fumigatus. Single-nucleotide polymorphisms (SNPs) associated with CCPA were found in TLR1, CLEC7A (dectin-1), PLAT (n=2), VEGFA, and DENND1B. Macrophages from CCPA patients showed low TLR3 and TLR10 expression and high TREM1 expression at baseline, as compared with macrophages from healthy subjects, with major expression differences being seen in most Toll-like receptors (TLRs) during 9 h of co-culture with A. fumigatus. The differences in baseline expression between the healthy and CCPA groups suggest roles for TLR3 and TLR10 in susceptibility to CCPA, and the association of SNPs in PLAT (n=2), VEGFA and DENND1B supports novel roles for plasminogen activation and angiogenesis and of these genes specifically in susceptibility to CCPA.

Scalable templated growth of graphene nanoribbons on SiC.

In spite of its excellent electronic properties, the use of graphene in field-effect transistors is not practical at room temperature without modification of its intrinsically semimetallic nature to introduce a bandgap. Quantum confinement effects can create a bandgap in graphene nanoribbons, but existing nanoribbon fabrication methods are slow and often produce disordered edges that compromise electronic properties. Here, we demonstrate the self-organized growth of graphene nanoribbons on a templated silicon carbide substrate prepared using scalable photolithography and microelectronics processing. Direct nanoribbon growth avoids the need for damaging post-processing. Raman spectroscopy, high-resolution transmission electron microscopy and electrostatic force microscopy confirm that nanoribbons as narrow as 40 nm can be grown at specified positions on the substrate. Our prototype graphene devices exhibit quantum confinement at low temperatures (4 K), and an on-off ratio of 10 and carrier mobilities up to 2,700 cm(2) V(-1) s(-1) at room temperature. We demonstrate the scalability of this approach by fabricating 10,000 top-gated graphene transistors on a 0.24-cm(2) SiC chip, which is the largest density of graphene devices reported to date.