Tests Of Small Airways Function Research Articles

Rapid Access Diagnostics for Asthma (RADicA): protocol for a prospective cohort study to determine the optimum series of investigations to diagnose asthma using conventional and novel tests

IntroductionThe diagnosis of asthma is often based on characteristic patterns of symptoms in the absence of an alternative explanation, resulting in over and under diagnosis. Therefore, diagnostic guidelines usually recommend...

Physiological tests of small airways function in diagnosing asthma: a systematic review

BackgroundAsthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed...

The Value of Fractional Exhaled Nitric Oxide and Forced Mid-Expiratory Flow as Predictive Markers of Bronchial Hyperresponsiveness in Adults with Chronic Cough

Bronchial provocation tests are standard for diagnosing the etiology of chronic cough, but they are time consuming and can induce severe bronchospasm. A safer and faster clinical examination to predict bronchial hyperresponsiveness (BHR) is needed. The objective of this study was to investigate whether small-airway function tests can predict BHR in adult patients with chronic cough. A retrospective, cross-sectional study of diagnoses made using spirometry and bronchial provocation test results was performed in 290 patients with chronic nonproductive cough. BHR-predictive values were analyzed via the area under receiver operating characteristic curves (AUCs). Optimal cutoff values were determined by maximizing the sum of sensitivity and specificity. Patients with chronic cough with BHR showed lower forced expiratory flow between 25% and 75% (FEF25%-75%), higher fractional exhaled nitric oxide (FENO), and a higher percentage of eosinophils in blood than patients without BHR (P < .0001 for all). The AUCs of FENO and FEF25%-75% for a BHR diagnosis were 0.788 (95% CI, 0.725-0.851) and 0.702 (95% CI, 0.641-0.763), respectively. Optimal cutoff values were 43 ppb for FENO and 78.5% for FEF25%-75%, with negative predictive values of 85.38% and 81.34%, respectively. The combined use of FENO and FEF25%-75% increased the AUC to 0.843 (95% CI, 0.794-0.892), significantly higher than either FENO (P= .012) or FEF25%-75% (P < .0001) alone. Small-airway dysfunction is present in patients with chronic cough and BHR. FEF25%-75% has value as a negative predictive parameter for BHR, especially when combined with FENO. FENO > 43 ppb and FEF25%-75% <78.5% strongly predicted a positive bronchial provocation test.

Effect of obesity on pulmonary function in asthmatic children of different age groups

To study the effect of obesity on pulmonary function in newly diagnosed asthmatic children of different age groups. Two hundred and ninety-four children with newly diagnosed asthma were classified into preschool-age (<6 years) and school-age (6 to 12.5 years) groups. They were then classified into obese, overweight, and normal-weight subgroups based on their body mass index (BMI). All the children underwent pulmonary function tests, including large airway function tests [forced vital capacity (FVC%) and forced expiratory volume in one second (FEV1%)] and small airway function tests [maximal expiratory flow at 25% of vital capacity (MEF25%), maximal expiratory flow at 50% of vital capacity (MEF50%), and maximal expiratory flow at 75% of vital capacity (MEF75%)]. The school-age group showed lower FEV1%, MEF25%, and MEF50% than the preschool-age group (P<0.05) after adjustment for sex and BMI. The normal-weight children in the school-age group had lower FEV1%, MEF25%, and MEF50% compared with their counterparts in the preschool-age group (P<0.05). The overweight children in the school-age group showed lower FVC% and MEF50% than those in the preschool-age group. However, all the pulmonary function parameters showed no significant differences between the obese children in the preschool-age and school-age groups. In the preschool-age group, FVC%, FEV1%, and MEF75% of the obese children were lower than those of the normal-weight children. In the school-age group, only FVC% and FEV1% showed differences between the obese and normal-weight children (P<0.05). The effect of obesity on the pulmonary function varies with age in children with asthma, and the effect is more obvious in those of preschool age.

Physiologic Characterization of the Chronic Bronchitis Phenotype in GOLD Grade IB COPD

Smokers with persistent cough and sputum production (chronic bronchitis [CB]) represent a distinct clinical phenotype, consistently linked to negative clinical outcomes. However, the mechanistic link between physiologic impairment, dyspnea, and exercise intolerance in CB has not been studied, particularly in those with mild airway obstruction. We, therefore, compared physiologic abnormalities during rest and exercise in CB to those in patients without symptoms of mucus hypersecretion (non-CB) but with similar mild airway obstruction. Twenty patients with CB (≥ 3 months cough/sputum in 2 successive years), 20 patients without CB but with GOLD (Global Initiative for Chronic Obstructive Lung Disease) grade IB COPD, and 20 age- and sex-matched healthy control subjects underwent detailed physiologic testing, including tests of small airway function and a symptom-limited incremental cycle exercise test. Patients with CB (mean ± SD postbronchodilator FEV1, 93% ± 12% predicted) had greater chronic activity-related dyspnea, poorer health-related quality of life, and reduced habitual physical activity compared with patients without CB and control subjects (all P < .05). The degree of peripheral airway dysfunction and pulmonary gas trapping was comparable in both patient groups. Peak oxygen uptake was similarly reduced in patients with CB and those without compared with control subjects (% predicted ± SD, 70 ± 26, 71 ± 29 and 106 ± 43, respectively), but those with CB had higher exertional dyspnea ratings and greater respiratory mechanical constraints at a standardized work rate than patients without CB (P < .05). Patients with CB reported greater chronic dyspnea and activity restriction than patients without CB and with similar mild airway obstruction. The CB group had greater dynamic respiratory mechanical impairment and dyspnea during exercise than patients without CB, which may help explain some differences in important patient-centered outcomes between the groups.

Current Approaches in Infant Pulmonary Function Testing

Pulmonary function testing in infants has grown from basic measurements of lung mechanics, volumes and breathing patterns to sophisticated measurements of forced expiratory flows, fractional lung volumes, and sensitive tests of small airway function. New tests continue to be developed that extend our understanding of lung function in health and disease. The indications for infant pulmonary function testing continue to be refined. This review highlights studies that involve some of the techniques, their role in detecting abnormalities in different conditions, and the information that they can provide about several diseases in recent years. Impediments to testing, including need for sedation, labor-intensive nature of the tests and lack of large normative data sets, remain obstacles for more widespread use of the techniques.

Comparison of the Structural and Inflammatory Features of COPD and Asthma Giles F. Filley Lecture

At least three conditions contribute to COPD. (1) Chronic bronchitis (mucous hypersecretion) is an inflammatory condition in which CD8+ T-lymphocytes, neutrophils, and CD68+ monocytes/macrophages predominate. The condition is defined clinically by the presence of chronic cough and recurrent increases in bronchial secretions sufficient to cause expectoration. There is enlargement of mucus-secreting glands and goblet cell hyperplasia, which can occur in the absence of airflow limitation. (2) Adult chronic bronchiolitis (small or peripheral airways disease) is an inflammatory condition of small bronchi and bronchioli in which there are predominantly CD8+ and pigmented macrophages. The functional defect is difficult to detect clinically but may be recognized by sophisticated tests of small airway function. There is mucous metaplasia, enlargement of the mass of bronchiolar smooth muscle, and loss of alveolar attachments. (3) Emphysema is an inflammatory condition of the alveoli in which T-lymphocytes, neutrophils, and pigmented alveolar macrophages are involved, associated with the release of excessive amounts of elastases. It is defined anatomically by permanent, destructive enlargement of airspaces distal to terminal bronchioli without obvious fibrosis. In contrast, asthma is a clinical syndrome characterized by allergic inflammation of bronchi and bronchioli in which CD4+ (helper) T-lymphocytes and eosinophils predominate. There is increased production and release of interleukin (IL)-4 and IL-5, which is referred to as a Th2-type response. There is usually increased tracheobronchial responsiveness to a variety of stimuli, and the condition is usually manifest as variable airflow obstruction. While differences between COPD and asthma have been highlighted, new data are emerging that indicate there may also be similarities.

Long-term Reproducibility of Tests of Small Airways Function: Comparisons with Spirometry

We used a tracking index to measure the reproducibility of single breath nitrogen test variables (CV/VC, CC/TLC, delta N2/L) and spirometric variables (FEV1 and FEV1/FVC) and to compare the characteristics of individuals whose pulmonary function tracks well with those whose pulmonary function tracks poorly. Data were derived from two cohorts followed longitudinally over a 9-11 year period. All variables were adjusted for age, sex and height by expressing them as Z-scores. In all smoking groups and in both cohorts, the tracking index was highest for FEV1, indicating that this variable was the most reproducible over the period of follow-up; delta N2/L and FEV1/FVC had very similar but slightly lower tracking indices; CV/VC consistently had the lowest tracking indices. Tracking indices were generally higher in smokers than in nonsmokers. The reproducibility of CC/TLC increased over the period of follow-up whereas the FEV1 reproducibility remained constant. We found no significant difference between those with high tracking indices and those with low indices in terms of sex, smoking status, prevalence of respiratory symptoms, history of respiratory disease, and rate of decline of FEV1. We conclude that FEV1 is the most reproducible of the variables examined, both within and between individuals, and that poor tracking or reproducibility are not related to smoking or to the presence of respiratory symptoms or disease.

FEV1 decline in asymptomatic young adults: relationships with some tests of small airways function

The aim of this study is to determine whether some tests proposed as diagnostic of small airways obstruction (SAO) are useful in identifying the subjects at risk of developing chronic airflow limitation. Eighty five healthy male workers (46 nonsmokers and 39 smokers, aged 21-41 yrs), living in the same area and not exposed to occupational pollutants were re-examined after an interval of 6 yrs. At the first survey 39 had functional evidence of SAO as determined by the presence of one of: maximal mid-expiratory flow (MMEF) less than 65% of predicted value (pred); maximal expiratory flow when 25% forced vital capacity remains to be expired (Vmax25) less than 60% pred; closing capacity (CC) greater than 130% pred; 46 had all functional values in the normal range. We considered four subgroups: smokers and nonsmokers with and without SAO. The rate of decline in FEV1, the decline in %delta FEV1 and delta FEV1.height-3, have been evaluated and compared in the subgroups. Initial values of specific tests (MMEF, Vmax25, CC and slope of phase III) have been examined for a possible relationship with decline of FEV1. Statistical analysis of our data showed that only CC was related to FEV1 decline. However, there were no significant differences in FEV1 decline among the subgroups. We conclude that in young adult subjects functional characteristics of SAO have no predictive value for development of chronic airways obstruction.

Respiratory epithelial permeability is unrelated to bronchial reactivity and small airway function in young smokers and nonsmokers

We studied eight young smokers and ten nonsmokers, to determine whether respiratory epithelial permeability to radiolabelled diethylenetriamine penta-acetate (99mTcDTPA) was related to small airway function or bronchial reactivity. Permeability was measured in inner (containing central airways) and outer lung zones by gamma camera. Lung-to-blood half-time (LB-T1/2) was corrected for blood background. Histamine was inhaled tidally (2 min inhalations) using doubling concentrations from 2 to 64 mg.ml-1. Results of small airway function tests, and of bronchial reactivity (expressed as the threshold concentration (reducing forced expiratory volume in one second (FEV1) by 2 SD), and as the percentage reduction in FEV1 after histamine 16 mg.ml-1) were similar in smokers and nonsmokers. LB-T1/2 was shorter in smokers than in nonsmokers in both inner (median (range) 21 (5.5-33) vs 63.5 (41-115) min; p less than 0.004) and outer (20.5 (5.5-30) vs 58.5 (39-105) min; p less than 0.004) zones. Neither inner nor outer zone LB-T1/2 was related to small airway function or bronchial reactivity. Bronchial reactivity and small airway tests may be abnormal in middle-aged smokers, but neither is related to the increased respiratory epithelial permeability of young smokers, in whom it appears too sensitive an index of airway integrity.

選択的肺胞気管支造影（ＳＡＢ）と末しょう気道狭さくの機能的診断法との対応

To evaluate the validity of scoring method of small airway function tests, selective alveolobronchography (SAB) was performed on 7 patients with bronchial asthma, 7 patients with chronic pulmonary emphysema and a patient with chronic bronchitis. The small airway lesion observed on SAB film was compared with the pulmonary function data including closing volume (CV), ΔN2/L, volume of isoflow (Visov) and ΔV50 and further with total score of the abnormalities in CV, ΔN2, Visov, and ΔV50 (SAO score).The severity of small airway lesion in SAB was expressed as the mean of maximum diameter/minimum diameter ratioes (ratio of bronchial diameter, RBD) in each 1cm-long segment on magnified film (3 to 4 fold).1. Significant but loose correlation was found between FEV1.0% and RBD, but correlation was not significant between respiratory resistance and RBD.2. Among small airway parameters, only CV was significantly correlated with RBD.3. Significant correlation was found between SAO score and RBD.We conclude that the scoring method of small airway function tests is meaningfull for evaluation of small airway obstruction.

Small airways function in nonsmokers with rheumatoid arthritis.

To evaluate the possible relationship between rheumatoid arthritis (RA) and airways dysfunction independent of cigarette smoking, we studied 19 lifetime nonsmokers with RA and 47 healthy nonsmokers. Ten tests of small airways function were administered to the subjects. In addition, diffusing capacity and static lung compliance were measured, and upstream airway conductance at mid-to-low lung volumes was calculated. Mean values were not significantly lower in the RA group than in the control group in any of the tests of small airways function. Three of the 19 (16%) patients with RA versus 15 of the 47 (32%) control subjects had abnormal findings on greater than 2 tests of small airways function (P greater than 0.1). Although mean diffusing capacity and static lung compliance were both within normal limits in each group, the former tended to be lower, while the latter was significantly lower, in the RA subjects. We conclude that airways dysfunction in RA, if present, is probably related to factors other than the underlying disease; if an association between RA and small airways abnormality is present in some patients, its prevalence is too small to have been detected in our sample.

Current Status of Small Airways Disease

The purpose of this review is to provide the clinician with a synthesis and evaluation of the available information about small airways disease. It will trace the development of the concept of small airways disease, review the work that has been done to evaluate the tests of small airways function, and synthesize the present thinking about the clinical importance of the small airways. This review is intended to highlight the information the clinican needs in order to make practical decisions about diagnosis and management.

Tests of Small Airway Function

Tests of Small Airway Function

The effects of intravenous infusion of saline on lung density, lung volumes, nitrogen washout, computed tomographic scans, and chest radiographs in humans.

In this study we examined the effect of a 15% increase in extracellular fluid volume on lung density, lung volumes, nitrogen washout, chest radiographs and computerized tomographic (CT) scans of the thorax in 5 volunteers. The objective of the study was to determine the sensitivity of these techniques in detecting small changes in lung water. Lung density was measured by a gamma ray Compton scatter technique and with an Ohio nuclear delta 2020 CT scanner. We measured or derived functional residual capacity, residual volume (RV), vital capacity (VC), and total lung capacity by helium dilution. Single-breath nitrogen washout was used to measure closing volume and the slope of phase III nitrogen washout (delta N2). Chest radiographs were taken in the posteroanterior and lateral projections. With the CT scanner we obtained slices 1 cm thick through the bases of the lungs and at 6 and 12 cm up from the bases. All these measurements were made before and 20 to 90 min after the intravenous infusion of 30 ml/kg body weight of warm saline over a period of 20 min. The most striking findings were a 24% increase in delta N2, a 14% increase in RV, and a 4.5% decrease in VC. Chest radiographs and the CT scans showed an increase in the size of the azygos veins. There was no change in Compton scatter density or the CT numbers. These results suggest that (1) tests of small airway function, such as RV and delta N2, are more sensitive than radiographic techniques to small increases in lung water, (2) there is some protection of the lung to increases in extracellular fluid volume.

Rapid improvement in abnormal pulmonary epithelial permeability after stopping cigarettes.

A new, non-invasive method of measuring pulmonary epithelial damage in man was compared with traditional tests of small-airway function. Pulmonary epithelial permeability was expressed as the half-time clearance from the lung into blood of (99m)Tc-diethylene triaminepenta-acetic acid ((99m)Tc-DTPA) deposited predominantly in the alveoli from an inhaled aerosol.Recovery from abnormal pulmonary permeability was recorded after stopping smoking for 21 days in a group of young symptomless cigarette smokers. Before stopping smoking there was a significant correlation between half-time lung clearance of (99m)Tc-DTPA and carboxyhaemoglobin concentration (r=0.69; p <0.05). There was no correlation between carboxyhaemoglobin value and closing volume, the only other abnormal test of airway function. Twenty-four hours after stopping smoking the mean half-time lung clearance of (99m)Tc-DTPA had increased significantly (p <0.001) from a baseline of 15.8 min (SEM 1.3 min) to 25.5 min (SEM 2.5 min). The mean half-time clearance continued to increase to a maximum of 35.5 min (SEM 3.1 min) at seven days, but was significantly less than the reported half-time clearance for non-smokers (59 min, SEM

Reevaluation of Tests of Small Airways Function

Because of the current, and recurrent, interest in the prognostic potential of tests of peripheral lung function, we have reassessed the results of using the single breath closing volume test in conjunction with measurements derived from the forced vital capacity (FVC) maneuver. Data were obtained as a part of the prospective longitudinal study of the natural history of obstructive lung disease based on a random sample of the population of Tucson, Arizona. 1 Lebowitz MD Knudson RJ Burrows B Tucson epidemiologic study of obstructive lung diseases. I: Methodology and prevalence of disease. Am J Epidemiol. 1975; 102: 137-152 PubMed Google Scholar The study began in 1972. Survey data included spirometric and flow-volume measurements. 2 Knudson RJ Slatin RC Lebowitz MD et al. The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. Am Rev Respir Dis. 1976; 113: 587-600 PubMed Google Scholar , 3 Knudson RJ Burrows B Lebowitz MD The maximal expiratory flow-volume curves: Its use in the detection of ventilatory abnormalities in a population study. Am Rev Respir Dis. 1976; 114: 871-879 PubMed Google Scholar The single breath test was employed in the second survey year, 4 Knudson RJ Lebowitz MD Burton AP et al. The closing volume test: Evaluation of nitrogen and bolus methods in a random population. Am Rev Respir Dis. 1977; 115: 423-434 PubMed Google Scholar and the fifth survey year was completed in the spring of 1979. The limit of normal was the “normal 95th percentile” for each measurement as previously described. 2 Knudson RJ Slatin RC Lebowitz MD et al. The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. Am Rev Respir Dis. 1976; 113: 587-600 PubMed Google Scholar , 4 Knudson RJ Lebowitz MD Burton AP et al. The closing volume test: Evaluation of nitrogen and bolus methods in a random population. Am Rev Respir Dis. 1977; 115: 423-434 PubMed Google Scholar

Reevaluation of Tests of Small Airways Function

Because of the current, and recurrent, interest in the prognostic potential of tests of peripheral lung function, we have reassessed the results of using the single breath closing volume test in conjunction with measurements derived from the forced vital capacity (FVC) maneuver. Data were obtained as a part of the prospective longitudinal study of the natural history of obstructive lung disease based on a random sample of the population of Tucson, Arizona.1 The study began in 1972. Survey data included spirometric and flow-volume measurements.

Intranasal immunization with attenuated live influenza vaccine in asthma

Attenuated live intranasal influenza vaccine (“Alice”) was given to 20 asthmatics and 9 control subjects. Pulmonary function tests were performed before and after, with emphasis on tests of small airways function (using flow volume curves with air and a helium-oxygen mixture). In subjects with a low influenza A antibody titer, there was a 4-fold rise in titer to the vaccine, whereas those subjects with a high titer showed no rise. There were no significant changes in pulmonary function in any parameters measured, and no significant symptoms were reported. We have concluded from this study that “Alice” appears safe for use in asthma and was capable of producing an antibody titer rise in persons with low titers.

ACUTE EFFECTS OF SMOKING TOBACCO AND A TOBACCO SUBSTITUTE ON LUNG FUNCTION IN MAN

The acute effects on airway function of smoking one cigarette of a tobacco substitute 'New Smoking Material' (NSM), one cigarette of conventional tobacco, and one cigarette containing 70% tobacco and 30% NSM, were studied in 6 healthy non-smokers and 6 healthy smokers. None of the cigarettes produced any change in three tests of small-airway function (flow-volume curves, closing volume, frequency dependence of compliance). However, smoking either one conventional tobacco cigarette or the 30% NSM/70% tobacco cigarette produced an acute fall in specific airways conductance, of similar degree with both cigarettes, whereas the 100% NSM cigarette produced no such change.