Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis.

BACKGROUND--Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. METHODS--Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. RESULTS--Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). CONCLUSIONS--The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.     

Validity of peak expiratory flow measurement in assessing reversibility of airflow obstruction.

BACKGROUND: Assessing the reversibility of airflow obstruction by peak expiratory (PEF) measurements would be practicable in general practice, but its usefulness has not been investigated. METHODS: PEF measurements were performed (miniWright peak flow meter) in 73 general practice patients (aged 40 to 84) with a history of asthma or chronic obstructive lung disease before and after 400 micrograms inhaled sulbutamol. The change in PEF was compared with the change in forced expiratory volume in one second (FEV1). Reversible airflow obstruction was analysed in two ways according to previous criteria. When defined as a 9% or greater increase in FEV1 expressed as a percentage of predicted values reversibility was observed in 42% of patients. Relative operating characteristic analysis showed that an absolute improvement in PEF of 60 l/min or more gave optimal discrimination between patients with reversible and irreversible airflow obstruction (the sensitivity and specificity of an increase of 60 l/min in detecting a 9% or more increase in FEV1 as a percentage of predicted values were 68% and 93% respectively, with a positive predictive value of 87%). When defined as an increase of 190 ml or more in FEV1, reversible airflow obstruction was observed in 53% of patients. Again an absolute improvement in PEF of 60 l/min or more gave optimal discrimination between patients with reversible and irreversible airflow obstruction (sensitivity 56%, specificity 94%, and positive predictive value 92%). CONCLUSION: Absolute changes in PEF can be used as a simple technique to diagnose reversible airflow obstruction in patients from general practice.     

Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency

BACKGROUND: Severe alpha(1)-antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency. METHODS: The AAT Genetic Modifier Study is a multicentre family-based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33-80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV(1)) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV(1) <50% predicted). RESULTS: In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV(1 )percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV(1) values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non-index cases (p<0.01). Men had lower pre- and post-bronchodilator FEV(1) percentage predicted than women (p<0.0001); the lowest FEV(1) values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non-index groups were examined separately, with men representing the majority of non-index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non-index men but not women. CONCLUSION: In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment.     

Effects of allergy and age on responses to salbutamol and ipratropium bromide in moderate asthma and chronic bronchitis.

The bronchodilating responses to 400 micrograms salbutamol and 80 micrograms ipratropium bromide were studied in 188 patients with chronic bronchitis (n = 113) or asthma (n = 75) and mild to moderate airflow obstruction (forced expiratory volume in one second (FEV1) above 50% but below 2 SD of predicted value) in a crossover study on two days a week apart. Both the patients with asthma and the patients with chronic bronchitis varied considerably in their responses to the salbutamol and the ipratropium bromide. The mean increase in FEV1 in the subjects with asthma was higher after salbutamol (0.371 or 18% of the prebronchodilator value) than after ipratropium bromide (0.26 1 or 13%). In chronic bronchitis there was no difference between the increase in FEV1 after salbutamol (0.161 or 7%) and after ipratropium bromide (0.191 or 8%). When patients were categorised into those with a better response to salbutamol 400 micrograms and those with a better response to ipratropium bromide 80 micrograms, patients with chronic bronchitis responded better in general to ipratropium bromide whereas asthmatic patients responded better to salbutamol. The response pattern was also related to allergy and age, allergic patients and patients under 60 being more likely to respond better to salbutamol 400 micrograms than non-allergic patients and older patients, who benefited more from ipratropium bromide 80 micrograms. The response pattern was not related to sex, smoking habits, lung function, bronchial reactivity, respiratory symptoms, or number of exacerbations during the preceding year.     

Randomised controlled trial of the effectiveness of a respiratory health worker in reducing impairment, disability, and handicap due to chronic airflow limitation.

A randomised controlled trial was undertaken to determine whether a respiratory health worker was effective in reducing the respiratory impairment, disability, and handicap experienced by patients with chronic airflow limitation attending a respiratory outpatient department. The 152 adults (aged 30-75 years) who participated had a prebronchodilator forced expiratory volume in one second (FEV1) below 60% predicted and no other disease. They were randomised to receive the care of a respiratory health worker or the normal services provided by the outpatient department. The respiratory health worker provided health education and symptom and treatment monitoring in liaison with primary care services. After one year there was little difference between the two groups in spirometric values (FEV1 and forced vital capacity before and after salbutamol 200 micrograms), disability (six minute walking distance and paced step test), and handicap (sickness impact profile, hospital anxiety and depression scale). Patients not looked after by the respiratory health worker were more likely to die (relative risk 2.9 (95% confidence limits 0.8, 10.2); when age and FEV1 were controlled for this risk increased to 5.5 (95% confidence limits 1.2, 24.5). Patients looked after by the respiratory health worker attended their general practitioner more frequently and were prescribed a greater range of drugs. This is the third study to have found limited measurable benefit in terms of morbidity from the intervention of a respiratory health worker. This may be due to the ability of such workers to keep frail patients alive.     

Expiratory flow-volume curves in mechanically ventilated patients with chronic obstructive pulmonary disease

BACKGROUND: Forced expiratory flow-volume curves are commonly used to assess the degree of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). In mechanically ventilated subjects, expiratory airways obstruction can only be estimated from relaxed expirations. The aim of this study was to quantify the degree of airways obstruction from relaxed expiratory flow-volume curves in mechanically ventilated patients with COPD. METHODS: As measure of airflow obstruction, the effective time constant during the last 50% of expired volume (tau) was calculated. For bedside monitoring, tau was recalculated as the slope of the flow during the last 50% of expired volume (SF50). In order to study reproducibility, the variables were calculated from consecutive breaths and at different levels of end-expiratory lung volume (EEV). The SF50 and the tau-were correlated with the forced expiratory volume in 1 s (FEV1) measured prior to the start of ventilatory support. RESULTS: Twenty-seven patients were studied with a FEV1 expressed as percentage predicted of 31 +/- 12% (mean +/- SD). The SF50 amounted to 19 +/- 10 degrees. A positive linear correlation was established between SF50 and the FEV1, (%pred), (r = 0.90, P < 0.0001). The tau showed an exponential relationship with FEV1 (%pred), (r2 = 0.78). From 5 consecutive breaths the mean variation coefficient of SF50 was 5 +/- 2%. Changes of delta EEV from 0.05 to 1.00 L did not affect the SF50-values. In 12 patients, mechanically ventilated for respiratory diseases other than COPD, mean tau and SF50 were significantly different from the COPD-patients (P < 0.0001). CONCLUSIONS: This study indicates that relaxed expiratory flow-volume curves can be used to assess airflow obstruction in mechanically ventilated patients with COPD. This information can be used to adapt ventilatory settings.     

Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction.

The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction.     

Lung sound intensity in patients with emphysema and in normal subjects at standardised airflows.

BACKGROUND: A common auscultatory finding in pulmonary emphysema is a reduction of lung sounds. This might be due to a reduction in the generation of sounds due to the accompanying airflow limitation or to poor transmission of sounds due to destruction of parenchyma. Lung sound intensity was investigated in normal and emphysematous subjects in relation to airflow. METHODS: Eight normal men (45-63 years, FEV1 79-126% predicted) and nine men with severe emphysema (50-70 years, FEV1 14-63% predicted) participated in the study. Emphysema was diagnosed according to pulmonary history, results of lung function tests, and radiographic criteria. All subjects underwent phonopneumography during standardised breathing manoeuvres between 0.5 and 2 1 below total lung capacity with inspiratory and expiratory target airflows of 2 and 1 l/s respectively during 50 seconds. The synchronous measurements included airflow at the mouth and lung volume changes, and lung sounds at four locations on the right chest wall. For each microphone airflow dependent power spectra were computed by using fast Fourier transformation. Lung sound intensity was expressed as log power (in dB) at 200 Hz at inspiratory flow rates of 1 and 2 l/s and at an expiratory flow rate of 1 l/s. RESULTS: Lung sound intensity was well repeatable on two separate days, the intraclass correlation coefficient ranging from 0.77 to 0.94 between the four microphones. The intensity was strongly influenced by microphone location and airflow. There was, however, no significant difference in lung sound intensity at any flow rate between the normal and the emphysema group. CONCLUSION: Airflow standardised lung sound intensity does not differ between normal and emphysematous subjects. This suggests that the auscultatory finding of diminished breath sounds during the regular physical examination in patients with emphysema is due predominantly to airflow limitation.     

Bronchial responsiveness to methacholine in chronic bronchitis: relationship to airflow obstruction and cold air responsiveness.

The response to inhaled methacholine is increased in patients with chronic airflow obstruction, but it is not known whether this is due to true hyperresponsiveness or is a result of the airflow obstruction. In asthmatics the response to methacholine correlates with the bronchoconstriction produced by hyperventilation of cold dry air. We studied 27 patients with a history of smoking and chronic bronchitis with a range of severity of airflow obstruction. Bronchial responses to methacholine (expressed as the provocation concentration causing a fall in FEV1 of 20%-PC20) and isocapnic hyperventilation of cold dry air were measured. In 19 patients the PC20 was less than 8 mg/ml (that is, in the asthmatic range) but only three developed bronchoconstriction in response to hyperventilation. There was a linear correlation between the log PC20 and the FEV1 (r = 0.86, p less than 0.001). The results suggest that in patients with chronic airflow obstruction the response to methacholine is determined by the degree of airflow obstruction, and cannot be used in the diagnosis of asthma in the absence of additional information.     

Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group.

BACKGROUND: There is no agreement on how a bronchodilator response should be expressed. Ideally, the index used should be able to distinguish asthma from chronic obstructive lung disease and be independent of initial FEV1. METHODS: Two hundred and seventy four adults (aged 18-60 years) outpatients with obstructive airways disease were studied. Patients were divided into syndrome groups on the basis of a standardised history: asthma (n = 99), asthmatic bronchitis (n = 88), and chronic obstructive lung disease (n = 51); 36 subjects could not be attributed to any subgroup. FEV1 was measured before and 20 minutes after inhalation of 1000 micrograms terbutaline. Different expressions of bronchodilator response (delta FEV1) were compared with respect to their dependence on initial FEV1 and their efficacy in separating subjects with asthma from those with chronic obstructive lung disease. delta FEV1 was expressed as a percentage of initial FEV1 (delta FEV1%init), absolute value (delta FEV1[1]), percentage of predicted FEV1 (delta FEV1%pred), standardised residual (delta SR-FEV1), and percentage of maximal possible increase (delta FEV1%[pred-init]). RESULTS: delta FEV1%init was more dependent on initial FEV1 (p = -0.405) than delta FEV1[1] (r = -0.145), delta FEV1%pred (r = -0.166), and delta SR-FEV1 (r = -0.127). delta FEV1%[pred-init] reached infinity when initial FEV1 approached predicted levels. delta FEV1%pred had a higher likelihood ratio (1.71) for separating patients with asthma from those with chronic obstructive lung disease than other expressions of bronchodilator response. Asthmatic patients had larger mean bronchodilator responses than patients in other subgroups; this difference was largest for delta SR-FEV1 (F = 9.19) and delta FEV1%pred (F = 9.03); it was much smaller for delta FEV1%init (F = 5.89). Despite significant differences in mean response, there was a large overlap of individual responses between diagnostic subgroups. The bronchodilator response was continuously and unimodally distributed for all expressions. CONCLUSIONS: delta FEV1%pred appears to be the most useful method of expressing bronchodilator response, both for clinical and for research purposes. Reversibility of airways obstruction in response to a bronchodilator is a continuous variable and not a dichotomous triat. Any cut off level of a "positive" bronchodilator response is therefore arbitrary.