Showing papers in "European Respiratory Journal in 1999"

Development and validation of a questionnaire to measure asthma control

Abstract: International guidelines on asthma management indicate that the primary goal of treatment should be optimum asthma control. The aim of this study was to develop and validate the Asthma Control Questionnaire (ACQ). The authors generated a list of all symptoms used to assess control and sent it to 100 asthma clinicians who were members of guidelines committees (18 countries). They scored each symptom for its importance in evaluating asthma control. From the 91 responses, the five highest scoring symptoms were selected for the ACQ. In addition, there is one question on beta2-agonist use and another on airway calibre (total questions=7). The ACQ was tested in a 9-week observational study of 50 adults with symptomatic asthma. The ACQ and other measures of asthma health status were assessed at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability of the ACQ was high (intraclass correlation coefficient (ICC)=0.90). The questionnaire was very responsive to change in asthma control (p<0.0001). Cross-sectional and longitudinal validity were supported by correlations between the ACQ and other measures of asthma health status being close to a priori predictions. In conclusion, the Asthma Control Questionnaire has strong evaluative and discriminative properties and can be used with confidence to measure asthma control.

Six minute walking distance in healthy elderly subjects

Abstract: The six minute walking distance (6MWD) test is a commonly used test to estimate functional exercise capacity in patients with chronic diseases including chronic obstructive lung disease. Surprisingly, no attempt has been made to establish normal values for the 6MWD. The aim of this study, therefore, was to evaluate the 6MWD in healthy elderly volunteers and to evaluate its determining factors. Fifty-one healthy subjects aged 50-85 yrs volunteered to participate in the trial. All subjects were free of diseases that could interfere with performance in a walking test. Tests were performed in a quiet 50-m long hospital corridor. Patients were encouraged every 30 s to continue walking as quickly as possible. Walking distance averaged 631+/-93 m and was 84 m greater in the male compared to female subjects (p<0.001). The 6MWD showed significant correlations with age (r=-0.51, p<0.01) and height (r=0.54, p<0.01). Stepwise multiple regression analysis showed that age, height, sex and weight were independent contributors to the 6MWD in healthy subjects, thus explaining 66% of the variability. It is concluded that the six minute walking distance can be predicted adequately using a clinically useful model in healthy elderly subjects. Its variability is explained largely by age, sex, height and weight. Results of the six minute walking distance may be interpreted more adequately if expressed as a percentage of the predicted value.

Physiological changes in respiratory function associated with ageing

Abstract: Physiological ageing of the lung is associated with dilatation of alveoli, enlargement of airspaces, decrease in exchange surface area and loss of supporting tissue for peripheral airways ("senile emphysema"), changes resulting in decreased static elastic recoil of the lung and increased residual volume and functional residual capacity. Compliance of the chest wall diminishes, thereby increasing work of breathing when compared with younger subjects. Respiratory muscle strength also decreases with ageing, and is strongly correlated with nutritional status and cardiac index. Expiratory flow rates decrease with a characteristic alteration in the flow-volume curve suggesting small airway disease. The ventilation-perfusion ratio (V'A/Q') heterogeneity increases, with low V'A/Q' zones appearing as a result of premature closing of dependent airways. Carbon monoxide transfer decreases with age, reflecting mainly a loss of surface area. In spite of these changes, the respiratory system remains capable of maintaining adequate gas exchange at rest and during exertion during the entire lifespan, with only a slight decrease in arterial oxygen tension, and no significant change in arterial carbon dioxide tension. Ageing tends to diminish the reserve of the respiratory system in cases of acute disease. Decreased sensitivity of respiratory centres to hypoxia or hypercapnia results in a diminished ventilatory response in cases of heart failure, infection or aggravated airway obstruction. Furthermore, decreased perception bronchoconstriction and diminished physical activity may result in lesser awareness of the disease and delayed diagnosis.

Development and validation of the Mini Asthma Quality of Life Questionnaire

Abstract: The 32-item Asthma Quality of Life Questionnaire (AQLQ) has shown good responsiveness, reliability and construct validity; properties that are essential for use in clinical trials, clinical practice and surveys. However, to meet the needs of large clinical trials and long-term monitoring, where efficiency may take precedent over precision of measurement, the 15-item self-administered MiniAQLQ has been developed. The MiniAQLQ was tested in a 9-week observational study of 40 adults with symptomatic asthma. Patients completed the MiniAQLQ, the AQLQ, the Short Form (SF)-36, the Asthma Control Questionnaire and spirometry at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability was very acceptable for the MiniAQLQ (intraclass correlation coefficient (ICC)=0.83), but not quite as good as for the AQLQ (ICC=0.95). Similarly, responsiveness in the MiniAQLQ (p=0.0007) was good but not quite so good as for the AQLQ (p<0.0001). Construct validity (correlation with other indices of health status) was strong for both the MiniAQLQ and the AQLQ. Criterion validity showed that there was no bias between the instruments (p=0.61) and the correlation between them was high (r=0.90). The Mini Asthma Quality of Life Questionnaire has good measurement properties but they are not quite as strong as those of the original Asthma Quality of Life Questionnaire. The choice of questionnaire should depend on the task at hand.

Pulmonary surfactant in health and human lung diseases: state of the art.

Abstract: Pulmonary surfactant is a complex and highly surface active material composed of lipids and proteins which is found in the fluid lining the alveolar surface of the lungs. Surfactant prevents alveolar collapse at low lung volume, and preserves bronchiolar patency during normal and forced respiration (biophysical functions). In addition, it is involved in the protection of the lungs from injuries and infections caused by inhaled particles and micro-organisms (immunological, non-biophysical functions). Pulmonary surfactant can only be harvested by lavage procedures, which may disrupt its pre-existing biophysical and biochemical micro-organization. These limitations must always be considered when interpreting ex vivo studies of pulmonary surfactant. A pathophysiological role for surfactant was first appreciated in premature infants with respiratory distress syndrome and hyaline membrane disease, a condition which is nowadays routinely treated with exogenous surfactant replacement. Biochemical surfactant abnormalities of varying degrees have been described in obstructive lung diseases (asthma, bronchiolitis, chronic obstructive pulmonary disease, and following lung transplantation), infectious and suppurative lung diseases (cystic fibrosis, pneumonia, and human immunodeficiency virus), adult respiratory distress syndrome, pulmonary oedema, other diseases specific to infants (chronic lung disease of prematurity, and surfactant protein-B deficiency), interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, and hypersensitivity pneumonitis), pulmonary alveolar proteinosis, following cardiopulmonary bypass, and in smokers. For some pulmonary conditions surfactant replacement therapy is on the horizon, but for the majority much more needs to be learnt about the pathophysiological role the observed surfactant abnormalities may have.

An independent association between obstructive sleep apnoea and coronary artery disease.

Abstract: Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Skovde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of > or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease.

Regulation of mucociliary clearance in health and disease.

Abstract: Airway secretions are cleared by mucociliary clearance (MCC), in addition to other mechanisms such as cough, peristalsis, two-phase gas-liquid flow and alveolar clearance. MCC comprises the cephalad movement of mucus caused by the cilia lining the conducting airways until it can be swallowed or expectorated. MCC is a very complex process in which many variables are involved, all of which may modify the final outcome. The structure, number, movement and co-ordination of the cilia present in the airways as well as the amount, composition and rheological properties of the periciliary and mucus layers are determinants of MCC. Physiological factors such as age, sex, posture, sleep and exercise are reported to influence MCC due to a change in the cilia, the mucus or the periciliary layer, or a combination of these. Environmental pollution is suspected to have a depressant effect on MCC dependent on different factors such as pollutant concentration and the duration of exposure. Most studies focus on sulphur dioxide, sulphuric acid, nitrogen dioxide and ozone. Tobacco smoke and hairspray have been noted to have a negative influence on MCC. Some diseases are known to affect MCC, mostly negatively. The underlying mechanism differs from one illness to another. Immotile cilia syndrome, asthma, bronchiectasis, chronic bronchitis, cystic fibrosis and some acute respiratory tract infections are among the most frequently reported. The present paper reviews normal mucociliary clearance and the effects of diseases on this process.

Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease

Abstract: The effect of bacterial colonization of the bronchi on the progress of airflow limitation is not well known. Therefore, the pattern of airway inflammation in smokers and patients with stable chronic obstructive pulmonary disease (COPD) and its relation to bronchial microbial colonization was assessed. Eight nonsmoking and 18 smoking controls as well as 52 patients with COPD (28 mild, 11 moderate and 13 severe) were studied. All subjects were investigated by means of flexible bronchoscopy including protected specimen brush and bronchoalveolar lavage (BAL) sampling. Differential cell counts, cytokine (interleukin (IL)-1beta, IL-6, IL-8, IL-10 and tumour necrosis factor-alpha(TNF-alpha) concentrations and microbial patterns were determined in BAL fluid. Forced expiratory volume in one second (FEV1) % of the predicted value was inversely correlated with pack-yrs of cigarette smoking (r=-0.47, p<0.0001), the percentage of neutrophil (p=-0.56, p<0.0001) and IL-6 (p=-0.37, p=0.01) and IL-8 concentration (p=-0.43, p=0.004) in BAL fluid. Accordingly, pk-yrs of cigarette smoking (p=0.39, p=0.01) and IL-8 (p=0.69, p<0.0001) and TNFalpha (p=0.4, p<0.005) were positively correlated with the percentage of neutrophils in BAL fluid. Smoking controls and COPD patients were mainly colonized in the bronchial tree (33%) by community endogenous potentially pathogenic micro-organisms (PPMs). Colonization rates and patterns of PPMs were not affected by severity of airflow obstruction. The presence of PPMs was significantly associated with higher percentages of neutrophils (33.2+/-10.4% versus 10.1+/-3.5%, p=0.02) and TNF-alpha concentration (29.9+/-10.8 versus 6.3+/-2.1 pg x mL(-1), p=0.01) in BAL fluid. In conclusion, bronchial neutrophilia is a key inflammatory pattern in chronic obstructive pulmonary disease patients. Bronchial colonization with potentially pathogenic micro-organisms may represent an independent stimulus for additional airway inflammation.

Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma. European Respiratory Society

Abstract: A Task Force supported by the European Respiratory Society was set up in 1997 in order to address the major issues relevant to difficult/therapy-resistant asthma. Although the group of patients involved is small in comparison to the high numbers of patients with asthma, these patients consume a significant proportion of medical resources in terms of both time and money [1]. The major issues facing the Task Force were how to define "difficult asthma", how the patient with difficult asthma should be evaluated, the pathophysiological mechanisms underlying difficult asthma and the treatments available. The Task Force also concerned itself with defining the areas of research necessary to bring about a greater understanding of the causes of difficult asthma and novel treatments. The document resulting from this Task Force represents a consensus of different opinions, which will form the basis for further research. Formulating the definition

Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial

Abstract: Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.

Defining asthma in epidemiological studies

Abstract: It has been suggested that, in epidemiological studies, asthma should be defined as symptomatic bronchial hyperresponsiveness (BHR). This paper critically examines the validity of this and alternative methods of defining asthma by reviewing population-based studies validating BHR and symptom questionnaires against asthma defined on the basis of a clinical assessment. It is emphasized that a single definition of asthma will not be applicable to all studies. When the aim of a study is to compare differences in prevalence of asthma between populations, Youden's Index (sensitivity + specificity - 1) is the best single measure of validity. BHR has similar or better specificity, but much worse sensitivity, and therefore a worse Youden's Index, than symptom questionnaires. When the aim is to estimate relative risks, the validity of the definition of asthma depends more on its positive predictive value. Therefore, more specific methods of detecting asthmatics, such as severe symptoms, diagnoses of asthma, or symptomatic BHR may be most useful in cohort and case-control studies. In contrast, conversely, the method of choice for the first phase of prevalence comparisons is standardized written or video symptom questionnaires. In order to explore reasons for the differences in asthma prevalence, and to estimate possible differential symptom reporting, questionnaires can be supplemented with bronchial hyperresponsiveness and other testing in subsamples of the symptomatic and nonsymptomatic subjects. However, symptoms and bronchial hyperresponsiveness should usually be analysed separately rather than combined due to the poor agreement between bronchial hyperresponsiveness and clinical asthma.

Risk factors for community-acquired pneumonia in adults: a population-based case-control study

Abstract: Although community-acquired pneumonia (CAP) remains a major cause of hospitalization and death, few studies on risk factors have been performed. A population-based case-control study of risk factors for CAP was carried out in a mixed residential-industrial urban area of 74,610 adult inhabitants in the Maresme (Barcelona, Spain) between 1993 and 1995. All patients living in the area and clinically suspected of having CAP at primary care facilities and hospitals were registered. In total, 205 patients with symptoms, signs and radiographic infiltrate compatible with acute CAP participated in the study. They were matched by municipality, sex and age with 475 controls randomly selected from the municipal census. Risk factors relating the subject's characteristics and habits, housing conditions, medical history and treatments were investigated by means of a questionnaire. In the univariate analysis, an increased risk of CAP was associated with low body mass index, smoking, respiratory infection, previous pneumonia, chronic lung disease, lung tuberculosis, asthma, treated diabetes, chronic liver disease, and treatments with aminophiline, aerosols and plastic pear-spacers. In multivariate models, the only statistically significant risk factors were current smoking of >20 cigarettes x day(-1) (odds ratio (OR)=2.77; 95% confidence interval (CI) 1.14-6.70 compared with never-smokers), previous respiratory infection (OR=2.73; 95% CI 1.75-4.26), and chronic bronchitis (OR=2.22; 95% CI 1.13-4.37). Benzodiazepines were found to be protective in univariate and multivariate analysis (OR=0.46; 95% CI 0.23-0.94). This population-based study provides new and better established evidence on the factors associated with the occurrence of pneumonia in the adult community.

Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification.

Abstract: Living conditions in eastern Germany have changed rapidly since unification in 1990 and little is known about how these changes affect the prevalence of atopic diseases. This study describes methods and prevalences of a large epidemiological project investigating determinants of childhood asthma and allergies in eastern (Dresden and Leipzig) and western (Munich) Germany in 1995/1996. Community based random samples of 9-11 yr old children in Dresden (n=3,017) and Munich (n=2,612), and of 5-7 yr old children in Dresden (n=3,300), Leipzig (n=3,167) and Munich (n=2,165) were studied by parental questionnaires, bronchial challenges with hypertonic saline, skin examination, skin-prick tests, and measurements of specific and total serum immunoglobulin (Ig)E using Phase II modules of the International Study of Asthma and Allergies in Childhood (ISAAC). In 9-11 yr old children, the prevalence of physician diagnosed asthma (7.9% versus 10.3%; p or = 1 allergen, and increased levels (>0.35 kU x L(-1)) of specific IgE against inhalant and food allergens. Symptoms and visible signs of atopic eczema tended to be more prevalent in Dresden. Similar East-West differences between the three study areas were seen in the younger age group. These findings are in line with recently observed increases in the prevalence of hay fever and atopic sensitization, but not of asthma and bronchial hyperresponsiveness, among 9-11 yr old children in Leipzig.

Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial

Abstract: The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi- squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p<0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates. Eur Respir J 1999; 13: 238-246.

Socioeconomic status, lung function and admission to hospital for COPD: results from the Copenhagen City Heart Study.

Abstract: This study analysed the effect of education and income on development of chronic obstructive pulmonary disease (COPD) assessing lung function and hospital admission. The study population consisted of 14,223 subjects, aged 20-90 yrs, randomly sampled from the population of Copenhagen in 1976. Association between socioeconomic factors and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at study entry was analysed by linear regression. The relation between socioeconomic factors and risk of admission to hospital for COPD from study entry until 1993 was assessed by register linkage. Education and income were independently associated with FEV1 and FVC. The age- and height-adjusted difference in FEV1 (mean+/-SEM) between the highest and lowest level of education and income was 259+/-31 mL in females and 400+/-39 mL in males. After additional adjustment for quantity and duration of smoking and inhalation, the difference was 220+/-31 mL and 363+/-39 mL in females and males, respectively. Results for FVC were of the same magnitude. Using a socioeconomic index which combined information on education and household income the association with lung function did not differ by age. A total of 219 females and 265 males were admitted to hospital for COPD during follow-up. Education and income were significantly associated with admission to hospital. After detailed adjustment for smoking the relative risks (95% confidence intervals) for medium and high versus low socioeconomic index in females were 0.74 (0.55-1.02) and 0.27 (0.10-0.73), respectively. Corresponding relative risks in males were 0.47 (0.36-0.63) and 0.35 (0.17-0.70). The results indicate that socioeconomic factors operating from early in life affect the adult risk of developing chronic obstructive pulmonary disease independently of smoking in both females and males.

Report of ERS Task Force: guidelines for measurement of acellular components and standardization of BAL.

Abstract: The investigatory technique of bronchoalveolar lavage(BAL) has become one of the most valuable research toolsfor studying inflammatory mechanisms in a wide range ofdiseases that affect the lungs and airways in humans, andseveral thousand peer review papers are published eachyear. In addition, cytological and microbiological testing ofBAL samples are of established value for assisting inclinical diagnosis and management of many lung diseases,and these procedures are available routinely in most mod-ern specialist respiratory centres. Yet despite its undoubtedvalue, the interpretation of BAL findings is still hinderedbecause the procedure cannot be precisely standardized. Inparticular, there is still no satisfactory method of deter-mining the dilution factor during lavage. This preventsaccurate quantification of all components in BAL fluidsand causes especial difficulty in interpreting the results ofmeasurements of soluble acellular components.A number of Task Force reports have been publishedthat have provided guidelines for the clinical application ofBAL, and on technical aspects mainly related to evaluationof cells and other cytological features [1–4]. However, noguidelines are currently available for evaluation of acell-ular components, nor are any firm recommendationsavailable for standardization of BAL procedure. Thepurpose of this editorial is to inform that this omission isnow addressed by a new report of a European RespiratorySociety (ERS) Task Force which is currently being pub-lished in the European Respiratory Review [5]. ThisReport provides a comprehensive review of the currentstatus of techniques for measurement of acellular com-ponents in human BAL samples, and gives guidelines andrecommendations to define standard procedures for thegeneral conduct of BAL. It updates previous guidelinesand gives recommendations on how to comply with theincreasing demands for more effective quality control.The Task Force was established by the BAL ScientificGroup of the ERS in September 1995. The authors wereprivileged to be the task force co-ordinators and editors ofthe report, to which 49 authors and 21 invited reviewersfrom 15 countries contributed. It contains a series of det-ailed critical reviews which give recommendations accord-ing to the consensus view on 17 topics. These include threesections concerned with the general problems of BALstandardization [6–8] and one section dealing with thespecial problems relating to children [9]; while the re-maining 13 sections provide detailed information on spe-cific considerations that apply to the measurement ofdifferent categories of specific components including pul-monary surfactant components [10], immunoglobulins[11], proteases and antiproteases [12], angiotensin-con-verting enzyme [13], antioxidants, oxidants and oxidationproducts [14], lipid mediators [15], cytokines [16], solu-ble adhesion molecules [17], markers of fibrosis [18],granulocyte derived markers [19], tumour markers [20],markers of cell death [21], and other acellular compo-nents [22]. Those beginning work on lavage will findinformation about problems and pitfalls and how best toavoid them, while those experienced in the field will findcomprehensive critical reviews to assist with selectingoptimal approaches. All are encouraged to agree to therecommendations for better standardization procedures,in order to facilitate multicentre studies and the clearercomparison of findings between different workers to aidclinical interpretation.Early BAL studies were focused mainly on defining thepredominant types of inflammatory cells associated withdifferent lung diseases. Despite concerns about the lack ofstandardization, it soon became apparent that the findingsfrom independent groups of workers were remarkablysimilar, provided that results were expressed as differentialBAL cell counts. This is because differential proportions ofcells, unlike concentrations per millilitre, are unaffected byvariable BAL dilution. The situation is more difficult foracellular components, because quantitative measurementsper millilitre are the main approach to expression of results.Despite the inaccuracies in quantification, the Task Forcereport shows that a great deal of valuable information hasbeen obtained about numerous acellular components inBAL samples and that reproducibility can be improved bya more informed approach to the methods used for expres-sion of results and by improvements in assay standard-ization. The current frequent variability of approaches usedby different workers may explain why the clinical utility ofmeasurements of acellular components in BAL remainspoorly defined compared to that of cellular components.This may change if future studies are conducted accordingto the guidelines proposed in the Task Force report toimprove the reproducibility and reliability of quantitativemeasurements. These are summarized in table 1.Applications of BAL have diversified into many fieldsof respiratory medicine, and it must therefore be em-phasized that the conventional BAL technique was not

A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients

Abstract: The beneficial effects of nocturnal oxygen therapy (NOT) in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate daytime hypoxaemia (arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)) and exhibiting sleep-related oxygen desaturation remains controversial. The effectiveness of NOT in that category of COPD patients was studied. The end points included pulmonary haemodynamic effects after 2 yrs of follow-up, survival and requirement for long-term oxygen therapy (LTOT). Seventy-six patients could be randomized, 41 were allocated to NOT and 35 to no NOT (control). The goal of NOT was to achieve an arterial oxygen saturation of >90% throughout the night. All these patients underwent polysomnography to exclude an associated obstructive sleep apnoea syndrome. The two groups exhibited an identical meansD daytime Pa,O2 of 8.4+/-0.4 kPa (63+/-3 mmHg) at baseline. Twenty-two patients (12 in the NOT group and 10 in the control group, p=0.98) required LTOT during the whole follow-up (35+/-14 months). Sixteen patients died, nine in the NOT group and seven in the control group (p=0.84). Forty-six patients were able to undergo pulmonary haemodynamic re-evaluation after 2 yrs, 24 in the NOT and 22 in the control group. In the control group, mean resting pulmonary artery pressure increased from 19.8+/-5.6 to 20.5+6.5 mmHg, which was not different from the change in mean pulmonary artery pressure in the NOT group, from 18.3+/-4.7 to 19.5+/-5.3 mmHg (p= 0.79). Nocturnal oxygen therapy did not modify the evolution of pulmonary haemodynamics and did not allow delay in the prescription of long-term oxygen therapy. No effect of NOT on survival was observed, but the small number of deaths precluded any firm conclusion. These results suggest that the prescription of nocturnal oxygen therapy in isolation is probably not justified in chronic obstructive pulmonary disease patients.

Multidisciplinary approach to management of postintubation tracheal stenoses.

Abstract: The optimal management of postintubation tracheal stenosis is not well defined. A therapeutic algorithm was designed by thoracic surgeons, ear, nose and throat (ENT) surgeons, anaesthetists and pulmonologists. Rigid bronchoscopy with neodymium-yttrium aluminium garnet (Nd-YAG) laser resection or stent implantation (removable stent) was proposed as first-line treatment, depending on the type of stenosis (web-like versus complex stenosis). In patients with web-like stenoses, sleeve resection was proposed when laser treatment (up to three sessions) failed. In patients with complex stenoses, operability was assessed 6 months after stent implantation. If the patient was judged operable, the stent was removed and the patient underwent surgery if the stenosis recurred. This algorithm was validated prospectively in a series of 32 consecutive patients. Three patients died from severe coexistent illness shortly after the first bronchoscopy. Of the 15 patients with web-like stenosis, laser resection was curative in 10 (66%). Among the 17 patients with complex stenoses, three remained symptom-free after stent removal. Bronchoscopy alone was thus curative in more than one-third of the patients. Six patients underwent surgery, two after failure of laser resection and four after failure of temporary stenting. Surgery was always performed with the patient in good operative condition. Palliative stenting was the definitive treatment in nine cases. Tracheostomy was the definitive solution in two cases. This approach, including an initial conservative treatment, depending on the type of the stenosis, appears to be applicable to almost all patients and allows secondary surgery to be performed with the patient in good condition.

Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers

Abstract: Interleukin (IL)-10 is a potent regulatory cytokine that decreases inflammatory responses. This study investigated whether IL-10 levels in the airway are decreased in chronic airway inflammation associated with asthma or chronic obstructive pulmonary disease (COPD). Sputum was obtained from 12 healthy nonsmokers, 10 healthy smokers, 16 asthmatic patients and seven patients with COPD by means of the sputum-induction method. The IL-10 level was measured via enzyme-linked immunosorbent assay and immunocytochemical analysis. The IL-10 level in sputum was significantly lower in asthma and COPD patients and healthy smokers compared with that in healthy nonsmokers (nonsmokers, 68.0+/-11.3; smokers, 45.3+/-7.8; asthma, 26.7+/-4.0; COPD, 18.0+/-2.3 pg x mL(-1); p<0.05 for nonsmokers versus the other groups). The percentage of IL-10-positive cells in the sputum was also significantly lower in asthma and COPD and in smokers (nonsmokers, 13.2+/-1.7; smokers, 6.4+/-1.8; asthma, 5.4+/-3.5; COPD, 3.5+/-1.6%; p<0.05 for nonsmokers versus the other groups). The IL-10-positive cell appeared morphologically to be the macrophage. These data suggest that the reduced level of interleukin-10 within the airways plays a role in the pathogenesis of chronic airway inflammation in asthma and chronic obstructive pulmonary disease.

Inner city air pollution and respiratory health and atopy in children.

Abstract: The impact of inner city air pollution on the development of respiratory and atopic diseases in childhood is still unclear. In a cross sectional study in Dresden, Germany, 5,421 children in two age groups (5-7 yrs and 9-11 yrs) were studied according to the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol. The prevalences of wheezing and cough as well as doctor diagnosed asthma and bronchitis were assessed by parental questionnaires. Children also underwent skin-prick testing, venipuncture for the measurement of serum immunoglobulin (Ig)E, lung function testing and a bronchial challenge test (4.5% saline) to assess airway hyperresponsiveness. Exposure was assessed on an individual basis by relating mean annual air pollution levels (SO2, NO2, CO, benzene, and O3) which had been measured on a 1 km2 grid, to the home and school address of each study subject. After adjusting for potential confounding factors an increase in the exposure to benzene of 1 microg x m3 air was associated with an increased prevalence of morning cough (adjusted odds ratio (aOR)): 1.15; 1.04-1.27) and bronchitis (aOR: 1.11; 1.03-1.19). Similar associations were observed for NO2 and CO. In turn, the prevalences of atopic sensitization, symptoms of atopic diseases and bronchial hyperresponsiveness were not positively associated with exposure to any of these pollutants. It is concluded that in this study a moderate increase in exposure to traffic-related air pollution was associated with an increased prevalence of cough and bronchitis, but not with atopic conditions in children.

What are minimal important changes for asthma measures in a clinical trial

Abstract: In this study, the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures, in order to identify the threshold where changes in clinical asthma measures are perceivable by patients. The study included 281 asthmatic patients, aged 18-63 yrs, in a randomized, placebo-controlled clinical trial of a leukotriene antagonist. Changes were related in: 1) asthma symptom scores; 2) inhaled beta-agonist use; 3) forced expiratory volume in one second (FEV1); and 4) peak expiratory flow (PEF) to a global question that queried overall change in asthma since starting the study drug. Additional analyses examined differences in the group reporting minimal improvement by treatment (active treatment versus placebo), sex and age groups. The average minimal patient perceivable improvement for each measure was: 1) -0.31 points for the symptom score on a scale of 0-6; 2) -0.81 puffs x day(-1) for inhaled beta-agonist use; 3) 0.23 L for FEV1; and 4) 18.79 L x min(-1) for PEF. In general placebo-treated patients and older patients, who reported minimal improvement, experienced less mean improvement from baseline than active-treated patients and younger patients, who reported minimal improvement. Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes. However, interpretation should be carried out cautiously when reporting a single value as a clinically important change.

Predisposing factors to bacterial colonization in chronic obstructive pulmonary disease

Abstract: The aim of this prospective observational study was to determine those factors influencing bacterial colonization in patients with stable chronic obstructive pulmonary disease (COPD). Eighty-eight outpatients with stable COPD and 20 patients with normal spirometry and chest radiography (controls) had a fibreoptic bronchoscopy performed with topical aerosol anaesthesia. Bacterial colonization was determined using the protected specimen brush (PSB) with a cut-off > or = 10(3) colony-forming units (CFU x mL(-1)). The influence of age, degree of airflow obstruction, smoking habit, pack-yrs of smoking, and chest radiographic findings on bacterial colonization were assessed by univariate and multivariate analysis. Significant bacterial growth was found in 40% of patients and in none of the controls. Haemophilus influenzae, Streptococcus viridans, S. pneumoniae and Moraxella catarrhalis were the most frequent pathogens. After adjustment for other variables, severe airflow limitation (odds ratio (OR) 5.11, 95% confidence interval (CI) 1.45-17.9) and current smoking (OR 3.17, 95% CI 2.5-8) remained associated with positive bacterial cultures. When only potentially pathogenic micro-organisms were considered, significant bacterial growth was found in 30.7% of patients, with severe airflow obstruction (OR 9.28, 95% CI 2.19-39.3) being the only variable independently associated with positive bacterial cultures. Our results show that stable chronic obstructive pulmonary disease patients have a high prevalence of bacterial colonization of distal airways which is mainly related to the degree of airflow obstruction and cigarette smoking.

Cephalometric abnormalities in non‐obese and obese patients with obstructive sleep apnoea

Abstract: The aim of this work was to comprehensively evaluate the cephalometric features in Japanese patients with obstructive sleep apnoea (OSA) and to elucidate the relationship between cephalometric variables and severity of apnoea. Forty-eight cephalometric variables were measured in 37 healthy males and 114 male OSA patients, who were classed into 54 non-obese (body mass index (BMI) or = 27 kg x m(-2), AHI=45.6+/-28.0 events h(-1)) groups. Diagnostic polysomnography was carried out in all of the OSA patients and in 19 of the normal controls. The non-obese OSA patients showed several cephalometric defects compared with their BMI-matched normal controls: 1) decreased facial A-P distance at cranial base, maxilla and mandible levels and decreased bony pharynx width; 2) enlarged tongue and inferior shift of the tongue volume; 3) enlarged soft palate; 4) inferiorly positioned hyoid bone; and 5) decreased upper airway width at four different levels. More extensive and severe soft tissue abnormalities with a few defects in craniofacial bony structures were found in the obese OSA group. For the non-obese OSA group, the stepwise regression model on AHI was significant with two bony structure variables as determinants: anterior cranial base length (S-N) and mandibular length (Me-Go). Although the regression model retained only linear distance between anterior vertebra and hyoid bone (H-VL) as an explainable determinant for AHI in the obese OSA group, H-VL was significantly correlated with soft tissue measurements such as overall tongue area (Ton), inferior tongue area (Ton2) and pharyngeal airway length (PNS-V). In conclusion, Japanese obstructive sleep apnoea patients have a series of cephalometric abnormalities similar to those described in Caucasian patients, and that the aetiology of obstructive sleep apnoea in obese patients may be different from that in non-obese patients. In obese patients, upper airway soft tissue enlargement may play a more important role in the development of obstructive sleep apnoea, whereas in non-obese patients, bony structure discrepancies may be the dominant contributing factors for obstructive sleep apnoea.

The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation

Abstract: Endotracheal tube colonization in patients undergoing mechanical ventilation was investigated. In the first part of this prospective study, the airway access tube was examined for the presence of secretions, airway obstruction and bacterial colonization, in cases undergoing extubation or tube change. In the second part of the study, the sequence of oropharyngeal, gastric, respiratory tract and endotracheal tube colonization was investigated by sequential swabbing at each site twice daily for 5 days in consecutive noninfected patients. In the first part, it was noted that all airway access tubes of cases undergoing extubation had secretions lining the interior of the distal third of the tube which were shown on scanning electron microscopy to be a biofilm. Gram-negative micro-organisms were isolated from these secretions in all but three cases. In the second part, it was noted that the sequence of colonization in patients undergoing mechanical ventilation was the oropharynx (36 h), the stomach (3660 h), the lower respiratory tract (60-84 h), and thereafter the endotracheal tube (60-96 h). Nosocomial pneumonia occurred in 13 patients and in eight cases identical organisms were noted in lower respiratory tract secretions and in secretions lining the interior of the endotracheal tube. The endotracheal tube of patients undergoing mechanical ventilation becomes colonized rapidly with micro-organisms commonly associated with nosocomial pneumonia, and which may represent a persistent source of organisms causing such infections.

Exhaled and nasal NO levels in allergic rhinitis: relation to sensitization, pollen season and bronchial hyperresponsiveness

Abstract: Exhaled nitric oxide is a potential marker of lower airway inflammation. Allergic rhinitis is associated with asthma and bronchial hyperresponsiveness. To determine whether or not nasal and exhaled NO concentrations are increased in allergic rhinitis and to assess the relation between hyperresponsiveness and exhaled NO, 46 rhinitic and 12 control subjects, all nonasthmatic nonsmokers without upper respiratory tract infection, were randomly selected from a large-scale epidemiological survey in Central Norway. All were investigated with flow-volume spirometry, methacholine provocation test, allergy testing and measurement of nasal and exhaled NO concentration in the nonpollen season. Eighteen rhinitic subjects completed an identical follow-up investigation during the following pollen season. Exhaled NO was significantly elevated in allergic rhinitis in the nonpollen season, especially in perennially sensitized subjects, as compared with controls (p=0.01), and increased further in the pollen season (p=0.04), mainly due to a two-fold increase in those with seasonal sensitization. Nasal NO was not significantly different from controls in the nonpollen season and did not increase significantly in the pollen season. Exhaled NO was increased in hyperresponsive subjects, and decreased significantly after methacholine-induced bronchoconstriction, suggesting that NO production occurs in the peripheral airways. In allergic rhinitis, an increase in exhaled nitric oxide on allergen exposure, particularly in hyperresponsive subjects, may be suggestive of airway inflammation and an increased risk for developing asthma.

Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children

Abstract: The role of repeated infections early in life in the development of childhood asthma and allergies has not been clarified. The aim of this study was to investigate the effect of repeated episodes of fever and antibiotic treatments during the first years of life on the prevalence of asthma, bronchial hyperresponsiveness (BHR), and atopy at school age in a representative population. Random samples of schoolchildren aged 5-7 yrs (n=7,545) and 9-11 yrs (n=7,498) were studied using the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol. To assess the prevalence of disease and early childhood exposures, parental questionnaires were administered (response rates 82.2% and 85.3%, respectively). In addition, children underwent skin prick tests, hypertonic saline challenge and blood sampling for the measurement of serum immunoglobulin (Ig)E. Repeated episodes of fever and antibiotic treatment in early life were strongly associated with the prevalence of asthma (odds ratio (OR)=7.95; 95% confidence interval (CI) 6.02-10.50) and current wheeze at school age. Within asthmatic children the number of fever episodes and antibiotic courses were strongly inversely related to the prevalence of atopy (OR=0.25; 95% CI 0.11-0.54 for skin test reactivity) and BHR (OR=0.31; 95% CI 0.10-0.92). Furthermore, asthmatic children with recurrent early childhood infections were at a lower risk of being symptomatic at school age. When considering atopic and nonatopic asthmatic children separately, the highest risk of asthma with repeated early childhood infections was found for nonatopic asthma (OR=24.29; 95% Cl 11.86-49.76). These findings suggest that a subgroup of children with a triggering or inducing of asthmatic symptoms through repeated early childhood infections exists within the "asthma syndrome" which has a better prognosis and is less related to the atopic phenotype.

Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease

Abstract: The present study investigated whether falls in environmental temperature increase morbidity from chronic obstructive pulmonary disease (COPD). Daily lung function and symptom data were collected over 12 months from 76 COPD patients living in East London and related to outdoor and bedroom temperature. Questionnaires were administered which asked primarily about the nature of night-time heating. A fall in outdoor or bedroom temperature was associated with increased frequency of exacerbation, and decline in lung function, irrespective of whether periods of exacerbation were excluded. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) fell markedly by a median of 45 mL (95% percentile range: -113-229 mL) and 74 mL (-454-991 mL), respectively, between the warmest and coolest week of the study. The questionnaire revealed that 10% had bedrooms <13 degrees C for 25% of the year, possibly because only 21% heated their bedrooms and 48% kept their windows open in November. Temperature-related reduction in lung function, and increase in exacerbations may contribute to the high level of cold-related morbidity from chronic obstructive pulmonary disease.

Long-term effectiveness of pulmonary rehabilitation in patients with chronic airway obstruction

Abstract: The aim of this study was to evaluate the long-term outcome of an outpatient pulmonary rehabilitation programme (PRP) in patients with chronic airway obstruction (CAO). In 61 CAO patients (35 asthmatics and 26 chronic obstructive pulmonary disease (COPD)) lung and respiratory muscle function, exercise tolerance (by symptom limited cycloergometer and walking tests), dyspnoea (Borg scale, visual analogue scale (VAS), baseline and transitional dyspnoea index (BDI and TDI, respectively)) and quality of life (St George's Respiratory Questionnaire (SGRQ)) were assessed at baseline (to), at discharge (t1) and 12 months postdischarge (t2). Preprogramme and post-programme hospital admissions and exacerbations of disease were also recorded. In comparison with baseline, no significant change was observed in lung function tests in either diagnostic group, either at t1 or at t2. In both groups improvements in respiratory muscle strength, exercise tolerance, Borg scale and VAS reported at t1 were partially reduced at t2. Analysis of variance showed that these changes over time were similar in the two groups. Mean values of SGRQ and BDI/TDI improved at t1, and, unlike exercise tolerance, did not worsen at t2. However, a clinically relevant difference in SGRQ between t2 and to was reported only in 56% of asthmatics and 52% of COPD patients. Compared with the preceding 2 yrs, in the year following PRP, hospital admissions and disease exacerbations decreased significantly in both diagnostic groups. Regardless of diagnosis, patients with chronic airway obstruction who underwent an outpatient pulmonary rehabilitation programme maintained an improved quality of life 12 months postdischarge despite a partial loss of the improvement in exercise tolerance.