Lung and thorax development during adolescence: relationship with pubertal status.

The aim of the present study was to define reference values for lung volumes and the lung transfer factor for carbon monoxide (TL,CO) for an adolescent population using thoracic volume index (TVI) and an index of pubertal stage in order to account for the variation in growth pattern between adolescents. TVI, pubertal stage by Tanner scale (PST), time since menarche, functional residual capacity measured using the helium-dilution technique, vital capacity, total lung capacity and TL,CO measured using a steady-state method were determined in 51 males (aged 13-20 yrs; PST T3-T5) and 52 females (aged 13-18 yrs; PST T2-T4; all but three had already undergone menarche). In male adolescents, height, weight, TVI, lung volumes and TL,CO increased with age. This was not the case in female adolescents. In males, the TVI was the independent variable that best correlated with pulmonary volumes. In females, height was the independent variable that best correlated with pulmonary volumes. In both sexes, the variable that best correlated with TL,CO was PST, associated with height in males. This cross-sectional study provides prediction equations for lung volumes and the lung transfer factor for carbon monoxide taking into account thoracic volume index and pubertal stage. It shows that, in adolescent males, lung and thoracic development occurs during and until the end of puberty. Conversely, in adolescent females, lung development is almost finished following menarche.     

Normal values for respiratory resistance using forced oscillation in subjects>65 years old.

The aim of the present study was to determine reference values and predictive variables for respiratory impedance (Zrs) by the forced oscillation technique (FOT) in subjects aged>65 yrs. The investigation involved a prospective study of nonsmoking subjects, with normal forced expiratory volumes. The Zrs parameters, which included average resistance between 4-16 Hz (R4-16), average resistance between 4-30 Hz (RM), resonant frequency (FN), capacitance (C) and inertance (I), were measured along with forced expiratory manoeuvres. Every subject had each parameter measured in the same sequence using FOT and spirometry. A total of 223 subjects aged 83+/-8 yrs were included in the study. The mean values for forced expiratory volume in one second (FEV1) % predicted were 110+/-23. The forced vital capacity (FVC) % pred was 114+/-21 and the FEV1/FVC % pred was 112+/-11. The mean values for the Zrs parameters were: R4-16: 0.25+/-0.07 kPa.s-1.L-1; RM: 0.25+/-0.06 kPa.s-1.L-1; FN: 11.0+/-2.8 Hz; I: 1.17+/-0.26 Pa.L-1.s-2; and C: 20.5+/-9.0 mL.hPa-1. In multiple regression models adjusted for age, sex, height and weight, height was the most influential predictor for Zrs parameters based on the magnitude of the regression coefficient. In conclusion, it was found that height was the best predictor for respiratory impedance parameters. Contribution of age and weight was negligible. However, the level of predictability for respiratory impedance parameters by regression equations was low.     

Should forced expiratory volume in six seconds replace forced vital capacity to detect airway obstruction?

It has been suggested that forced expiratory volume in six seconds (FEV(6)) should be substituted for forced vital capacity (FVC) to measure fractions of timed expired volume for airflow obstruction detection. The present authors hypothesised that this recommendation might be questionable because flow after 6 s of forced expiration from more diseased lung units with the longest time constants was most meaningful and should not be ignored. Furthermore, previous studies comparing FEV(6) and FVC included few subjects with mild or no disease. The present study used spirometric data from the USA Third National Health and Nutrition Evaluation Survey with prior published ethnicity- and sex-specific equations for FEV(1)/FEV(6), FEV(1)/FVC and FEV(3)/FVC, and new equations for FEV(3)/FEV(6), all derived from approximately 4,000 adult never-smokers aged 20-80 yrs. At 95% confidence intervals, 21.3% of 3,515 smokers and 41.3% of smokers aged >51 yrs had airway obstruction; when comparing FEV(1)/FEV(6) with FEV(1)/FVC, 13.5% were concurrently abnormal, 1.5% were false positives and 4.1% were false negatives; and when comparing FEV(3)/FEV(6) with FEV(3)/FVC, 11.6% were concurrently abnormal, 3.3% were false positives and 5.7% were false negatives. Substituting forced expiratory volume in six seconds for forced vital capacity to determine the fractional rates of exhaled volumes reduces the sensitivity of spirometry to detect airflow obstruction, especially in older individuals and those with lesser obstruction.     

Asthma mortality in Russia between 1980 and 1989.

There is evidence that mortality due to asthma has increased in a number of nations over the last two decades. This study was conducted to assess asthma mortality rates in Russia from 1980 to 1989. Data obtained were compared with figures from other countries. National asthma deaths were obtained from the Ministry of Health of the Russian Federation. Age- and sex-specific rates per 100,000 population per year were adjusted to the European population. Annual changes in mortality rates for the study period were estimated by linear regression analysis. Between 1980 and 1989, asthma mortality rates per 100,000 population per year increased from 3.7 to 5.3 in the total Russian population. Differences according to age and sex were observed. Asthma deaths increased with age and in most cases males showed higher death rates than females. There was a statistically significant annual increase in mortality rates for young males < 5 yrs of age and for adult males aged 35-64 yrs, as well as for females aged > or = 65 yrs. Asthma mortality rates in Russia between 1980 and 1989 may be considered moderate as compared with death rates reported for the same period in other countries.     

Physical exercise, sports, and lung function in smoking versus nonsmoking adolescents.

Associations between adolescent smoking habits and exercise, particularly participation in sports and lung function were studied. All students aged 13-19 yrs in Nord-Tr?ndelag County, Norway, 1995-1997, were invited to join a cross-sectional study. Information on smoking habits and exercise was obtained by self-administered questionnaire. Spirometry was performed in accordance with American Thoracic Society standards. Of the 6,811 students (aged 13-18 yrs, without asthma), 2,993 (44%) reported never-smoking, and 1,342 (20%) reported current smoking (90% daily). Frequency of physical exercise was inversely associated with smoking, but participants in individual sports with lesser endurance, especially body-building and fighting sports, were more likely to be daily smokers than nonparticipants. Both daily (53%) and occasional smokers (43%) were more likely to have quit sports than never-smokers (26%)). Never-smokers showed a positive dose-response between physical exercise and lung function (forced vital capacity and forced expiratory volume in one second, adjusted for age and height). No similar significant association was observed in daily smokers. These data suggest that smoking habits in different sports should be considered when promoting physical activity as smoking prevention, and sports organizations should include smoking prevention programmes. Adolescents with better lung function may self-select into sports; this possibility needs to be studied in a longitudinal design.     

Prediction equations for normal and low lung function from the Health Survey for England.

The aim of this study was to derive new spirometric reference equations for the English population, using the 1995/1996 Health Survey for England, a large nationally representative cross-sectional study. The measurements used were the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of a sample of 6,053 "healthy" (nonsmokers with no reported diagnosis of asthma or respiratory symptoms) White people aged > or = 16 yrs. Multiple regression analysis, with age and height as predictors, was carried out to estimate prediction equations for mean FEV1, FVC and FEV1/FVC, separately for males and females. A method based on smoothing multiple estimates of the fifth percentiles of residuals was used to derive prediction equations for the lower limit of normal lung function. The new equations fit the current English adult population considerably better than the European Coal and Steel Community equations, and the proportions of people with "low" (below the fifth percentile) lung function are closer to those expected throughout the whole adult age range (16 to > 75 yrs). For the age ranges the studies share in common, the new equations give estimates close to those derived from other nonlinear equations in recent studies. It is, therefore, suggested that these newly developed prediction equations be used for the White English population in both epidemiological studies and clinical practice.     

The effects of body weight on airway calibre.

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing. Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28-30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight.height(-2)) and Gaw (after adjustment for FRC) by multiple linear regression, separately for females and males. For males and females, BMI (+/-95% confidence interval) was 27.0+/-4.6 kg.m(-2) and 25.6+/-6.0 kg.m(-2) respectively, Gaw was 0.64+/-0.04 L.s(-1).cmH2O(-1) and 0.57+/-0.03 L.s(-1).cmH2O(-1), and FRC was 85.3+/-3.4 and 84.0+/-2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely with Gaw in males, but only weakly in females. In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.     

What factors explain racial differences in lung volumes?

In order to examine the physical characteristics that may determine racial differences in lung volumes, we studied healthy, nonsmoking Caucasian, Chinese and Indian males of similar ages (range 18-51 yrs). We measured spirometric function, flow volume curves, lung volumes, inspiratory and expiratory muscle pressures, alveolar distensibility and diffusing capacity, together with height, weight and fat free mass. Chest shape was measured using radiographs. The mean total lung capacity and vital capacity in the Caucasian group, expressed as percentage predicted, were 5 and 10% higher than in the Chinese group and 17 and 20% higher than in the Indian group. Chinese values for these measurements were 12 and 10% greater than Indian. We found that Caucasians had higher fat free masses, higher inspiratory and expiratory muscle pressures and wider chests than the other races. The Caucasians and Chinese had longer chests than the Indians. There was no difference in alveolar distensibility or in the diffusion coefficient between the groups. These findings suggest that Caucasians have larger lung volumes than Chinese and Indians because they have increased numbers of alveoli and physically larger chest cavities, and not because of greater alveolar distensibility. Chest dimensions, together with height and race explained 90% of the variation in forced vital capacity and 86% of the variation in total lung capacity. Height multiplied by fat free mass, a "physique factor", previously suggested as the best predictive factor for forced vital capacity in Caucasians, did not account for much of the variation in forced vital capacity between Caucasians and Indians, presumably because it takes no account of differences in chest dimensions.     

Lung function in adolescents after uncomplicated whooping cough in childhood

Ventilatory function (forced vital capacity, forced expiratory volume in one second, forced expiratory flows), static lung volumes, phase III slope and closing volume (single-breath nitrogen washout test) were measured in 499 children and adolescents aged 10-16 yrs from a general population sample in North-East France. A history of whooping cough was given by 44 children (22 of each sex); their results were compared to those of the 455 children (215 girls) with a negative history. The only difference between the two groups was a minimal increase in the residual volume/total lung capacity ratio in cases (19.2 +/- 3.1 vs 18.0 +/- 2.9%). We conclude that uncomplicated whooping cough in early childhood did not lead to significant pulmonary function abnormality in this population of children born after 1967.     

Daily versus weekly azithromycin in cystic fibrosis patients.

Four randomised, placebo-controlled trials have previously documented the clinical benefits of azithromycin (AZM) in cystic fibrosis (CF) patients. The present study examined whether the beneficial effect of AZM is equivalent when administered daily or weekly. A double-blind, randomised study was carried out in 208 CF patients aged 6-58 yrs who were assigned to AZM either 250 mg daily (n = 103) or 1,200 mg weekly (n = 105) for 6 months, with assessments at baseline and at 1, 3, 6 and 7 months. Patients were taken from five adult and children CF centres in South-east Queensland, Australia. Equivalence was demonstrated between the two groups (daily versus weekly) with respect to improvements in lung function (forced expiratory volume in one second and forced vital capacity), C-reactive protein, days spent in hospital, admission rates and nutrition (body mass index, z-scores) using 95% confidence intervals with a tolerance interval of +/-10%. In patients aged <18 yrs the daily group had significantly better improvements in z-scores for height and weight after 6 months. In children, a nutritional advantage for daily administration was found. Gastro-intestinal adverse effects were more common with weekly therapy. Apart from these findings, daily and weekly administered azithromycin demonstrated similar outcomes for cystic fibrosis patients.     

Age standardization in mapping adult overweight and obesity trends in the WHO European Region

This study aims to improve comparability of available data within the World Health Organization (WHO) European Region taking into account differences related to the aging of the population. Surveys were included if they were conducted on adults aged 25-64 years between 1985 and 2010 in the WHO European Region. Overweight/obesity prevalences were adjusted to the European standard population aged 25-64. Data were entered for each of the 5-year categories between 1981 and 2010. Measured height and weight data were available for males in 16 and females in 24 of the 53 countries. The 50-64-year-olds had higher prevalence of overweight and obesity as compared to the 25-49-year-olds. This pattern occurs in every country, by male and female, in almost all surveys. Age-standardized overweight prevalence was higher among males than females in all countries. Trend data showed increases in most countries. Age-standardized maps were based on self-reported data because of insufficient availability of measured data. Results showed more countries with available data as well as the higher category of obesity in the later surveys. Measured values are needed and age adjustment is important in documenting emerging overweight and obesity trends, independent of demographic changes, in the WHO European Region.     

Performance of forced expiratory manoeuvre in children.

The negative expiratory pressure (NEP) method has been previously used to assess the performance of forced vital capacity (FVC) manoeuvre in normal adults. The aim of the present study is to assess whether flow limitation is achieved during FVC manoeuvres in children aged 6-14 yrs. NEP (-10 cmH2O) was successfully applied in 177 normal children, the portion of FVC over which expiratory flow did or did not change with NEP being taken as effort-dependent and effort-independent, respectively. In all children peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) increased with NEP, indicating that PEF was in the effort-dependent portion of FVC. This portion decreased significantly with age (50-20% of FVC from 6-14 yrs). It is suggested that this mainly reflects the poorer coordination of specialized motor acts in younger children because of incomplete morphological and functional maturation of the relevant central nervous system (CNS) mechanisms. The results indicate that most unexperienced children aged 6-14 yrs can perform acceptable forced vital capacity manoeuvres, eventually achieving flow limitation over a portion of the forced vital capacity that increases with age. The negative expiratory pressure method can be used for online assessment of the performance of forced vital capacity manoeuvres and evaluation of treatment-related effects.     

Pulmonary gas exchange and educational level: a community study.

Socio-economic status (SES) is related to increased risk of airway disease in terms of forced expiratory volume in one second (FEV1) and forced vital capacity. No data are available as to what extent SES predicts alveolar function in a general population. In this cross-sectional study, 1,275 subjects aged 18-73 yrs underwent pulmonary testing, including the single-breath carbon monoxide transfer capacity of the lungs (TL,CO). Educational level was used as an index for SES. Mean +/- SD TL,CO % predicted was 97% among those with primary school education, 99% among those with secondary school education and 104% among those with a university degree. In a multiple linear regression analysis, adjusting for age, height, haemoglobin, carboxyhaemoglobin, smoking habits, occupational exposure, FEV1 and body mass index, TL,CO was significantly related to educational level in males but not in females. Occupational exposure was not significant. In this study, socio-economic status was found to be an independent determinant of TL,CO. Even in an affluent country such as Norway, socio-environmental risk factors may differ based on individuals' SES. Such risk factors may, for instance, be higher exposure to airborne pollutants, poorer housing conditions, or lower consumption of fruit and vegetables. Further exploration is called for.     

Effects of sex on sleep-disordered breathing in adolescents.

This study was conducted to determine the influence of puberty on features of sleep-disordered breathing (SDB) in adolescents. The study was performed in a general population sample of 226 adolescents of both sexes (aged 11-19 yrs) recruited from the secondary school population of the city of Seville, Spain. Subjects were divided into two groups: 1) postpubertal, i.e. females who had undergone menarche and males in whom axillary hair development or peak height velocity had occurred > 1 yr before the study; and 2) peripubertal, i.e. females who had not undergone menarche and males who had not developed axillary hair nor reached peak height velocity, or subjects in whom these pubertal changes had appeared < 1 yr before the study. All subjects answered a questionnaire on SDB and underwent overnight cardiorespiratory polygraphy. There were 50 males and 40 females (mean +/- SD age 13.5 +/- 1.2 yrs) in the peripubertal group, and 54 males and 82 females (age 16.3 +/- 1.7 yrs) in the postpubertal group. Males exhibited significantly higher neck circumference/height index and waist/hip index than females in both the peripubertal and postpubertal groups. In the postpubertal group, snoring and polygraphic alterations (respiratory events and oximetric parameters) were significantly more frequent in males than in females. Postpubertal adolescents showed sex differences in clinical and polygraphic parameters that were not observed at earlier pubertal stages. These findings support the influence of sex hormones on sex differences in sleep-disordered breathing.     

Sensitization to individual allergens and bronchial responsiveness in the ECRHS. European Community Respiratory Health Survey.

Little is known about the relation of bronchial responsiveness (BHR) to sensitization to individual allergens, or its variation between countries. Data were obtained for BHR, specific immunoglobulin E and confounding variables from 11,215 subjects, aged 20-44 yrs at the start of the European Community Respiratory Health Survey, in 34 centres in 15 countries. The relation of BHR to sensitization to cat, house dust mite, timothy grass and Cladosporium was estimated by means of multiple regression for each centre, and combined across centres by random effects meta-analysis, controlling for baseline lung function, height, sex, season of testing, age, smoking and age/sex and age/smoking interactions. BHR was greater, on average, in those sensitized to cat (p=0.023), house dust mite (p<0.001) and timothy grass (p=0.018), but not to Cladosporium (p=0.60), and increased with degree of sensitization (p<0.001). All relations showed heterogeneity between centres, although to a lesser extent in the relation to sensitization to house dust mite. More variation in bronchial responsiveness was explained by sensitization and degree of sensitization to the individual allergens than by atopy defined as any positive test in each centre, but the relative importance of each allergen varied. The use of atopy as a single variable in relation to bronchial hyperresponsiveness may be misleading.     

Spirometric reference equations for European females and males aged 65-85 yrs.

The aim of this study was to describe spirometric reference equations for healthy never-smoking European adults aged 65-85 yrs and to compare the predicted values of this sample with those from other studies including middle-aged and/or older adults. Reference equations and normal ranges for forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory volume in six seconds (FEV6), FEV1/FVC ratio and FEV1/FEV6 ratio were derived from a healthy subgroup of 458 subjects aged 65-85 yrs. Spirometry examinations followed the 1994 American Thoracic Society recommendations and the quality of the data was continuously monitored and maintained. Reference values and lower limits of normal were derived using a piecewise polynomial model with age and height as predictors. The reference values of FEV1 and FVC from the present study were higher than those given by prediction equations from the European Community for Coal and Steel. By contrast, use of prediction equations from Caucasian-American elderly subjects (Cardiovascular Health Study) consistently overpredicted FVC and FEV1 in females by 8.5 and 2.1%, respectively. In males, equations from the Cardiovascular Health Study overpredicted FVC by 2.8%, whilst underpredicting FEV1 by 2.5%. In conclusion, these results underscore the importance of using prediction equations appropriate to the origin, age and height characteristics of the subjects being studied.     

Respiratory impedance in children with cystic fibrosis using forced oscillations in clinic.

Measurement of lung function is an important component of clinical management in cystic fibrosis (CF), but has been difficult in young children. The present study aimed to characterise the utility of the forced oscillation technique for measurement of lung function in preschool-aged children with CF in a routine clinical setting. Lung function was assessed in 56 young children (aged 2-7 yrs) with CF. Respiratory system resistance (R(rs)) and reactance (X(rs)) at 6, 8 and 10 Hz were measured and expressed as Z-scores. Children were classified as asymptomatic or symptomatic based on an administered respiratory questionnaire and physical examination at the time of testing. Between-test repeatability was assessed in 25 children. Measurement of lung function using the forced oscillation technique was feasible in the CF clinic. The children with CF, as a group, had Z-scores for R(rs) at 6 Hz (R(rs,6)) R(rs,8), R(rs,10), X(rs) at 6 Hz (X(rs,6)) and X(rs,8) that were significantly different from zero. Children with current symptoms showed significantly decreased X(rs) and increased R(rs,6) compared with asymptomatic children. Measurement of lung function using the forced oscillation technique is feasible in young children with cystic fibrosis in a clinical setting. The technique has the potential to improve knowledge concerning early cystic fibrosis lung disease.     

Spirometry and chest wall dimensions in achondroplasia

Standard values for pulmonary function in short-limbed dwarfism are not available. Therefore, chest diameters and expiratory spirograms were measured in 58 female and 44 male subjects between 7 and 60 years of age with achondroplasia, the most common form of dwarfism. Standing height in adults was 49.6 +/- 3.2 (SD) inches with a sitting/standing height ratio of 0.66 (normal 0.52-0.53). Despite extremely short stature, only AP chest diameters in males were smaller than control subjects of similar age. The following equations were derived for forced vital capacity (FVC): males (under 25 years), FVC(L) = -3.56 + 0.162 X sitting height (in) + 0.067 X age (yrs); males (over 25 years), FVC(L) = -0.73 + 0.162 X sitting height (in) -0.047 X age (yrs); females (under 20 years), FVC(L) = -3.56 + 0.150 X sitting height (in) + 0.067 X age (yrs); females (over 20 years), FVC(L) = -1.92 + 0.150 X sitting height (in) -0.016 X age (years). Similar prediction equations were derived for FEV1 and FEF25-75%: FEV1/FVC % was 84.2 (+/- 6.5) for females and 88.0 (+/- 6.5) for males. We also compared the observed FVC measurements to values calculated using standing heights derived from the subject's sitting height, assuming a normal body proportion. The observed vital capacity in achondroplasia was only 67.6 (+/- 19.2) percent of that predicted for normally proportioned females and 72.4 (+/- 13.6) percent for males, suggesting reduced vital capacity in achondroplasia, due to reduced chest wall compliance or abnormal lung growth.     

An epidemiological study of pulmonary arterial hypertension.

All hospitalisations for pulmonary arterial hypertension (PAH) in the Scottish population were examined to determine the epidemiological features of PAH. These data were compared with expert data from the Scottish Pulmonary Vascular Unit (SPVU). Using the linked Scottish Morbidity Record scheme, data from all adults aged 16-65 yrs admitted with PAH (idiopathic PAH, pulmonary hypertension associated with congenital heart abnormalities and pulmonary hypertension associated with connective tissue disorders) during the period 1986-2001 were identified. These data were compared with the most recent data in the SPVU database (2005). Overall, 374 Scottish males and females aged 16-65 yrs were hospitalised with incident PAH during 1986-2001. The annual incidence of PAH was 7.1 cases per million population. On December 31, 2002, there were 165 surviving cases, giving a prevalence of PAH of 52 cases per million population. Data from the SPVU were available for 1997-2006. In 2005, the last year with a complete data set, the incidence of PAH was 7.6 cases per million population and the corresponding prevalence was 26 cases per million population. Hospitalisation data from the Scottish Morbidity Record scheme gave higher prevalences of pulmonary arterial hypertension than data from the expert centres (Scotland and France). The hospitalisation data may overestimate the true frequency of pulmonary arterial hypertension in the population, but it is also possible that the expert centres underestimate the true frequency.     

Distribution of technetium-99m-labelled QVAR delivered using an Autohaler device in children.

QVAR, an extrafine hydrofluoroalkane/beclomethasone dipropionate formulation, has been shown to double lung deposition in adults. The aim of the present study was to assess the total body deposition and distribution of technetium-99m-labelled (99mTc) QVAR in children after inhalation via an Autohaler. Sixteen male asthmatic children (5-14 yrs) inhaled labelled drug (<4 MBq 99mTc; 100 microg beclomethasone dipropionate) via an Autohaler within 30 min after salbutamol (200 microg) administration. Simultaneous anterior and posterior planar scintigraphic scans (120 s acquisition time) were collected after inhalation of labelled drug. Mean+/-SD lung deposition of labelled drug (attenuation-corrected; percentage of ex-actuator dose) was 36.9+/-9.2, 46.5+/-11.6 and 54.1+/-10.7% in children aged 5-7, 8-10 and 11-14 yrs, respectively. Combined oropharyngeal and gastrointestinal deposition was 59.7+/-8.2, 48.9+/-12.3 and 40.3+/-11.8%. Lung deposition positively correlated with the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Gastrointestinal dose negatively correlated with the FEV1, FVC, height and age. In older children (11-14 yrs), lung deposition was almost identical to that reported in adults using QVAR. In children aged 5-10 yrs, lung deposition using QVAR was greater than the levels measured using other commercial aerosol delivery systems. Oropharygeal and gastrointestinal deposition was inversely related to age.